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1.
Scand J Trauma Resusc Emerg Med ; 32(1): 57, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886775

RESUMEN

BACKGROUND: Limited research has explored the effect of Circle of Willis (CoW) anatomy among blunt cerebrovascular injuries (BCVI) on outcomes. It remains unclear if current BCVI screening and scanning practices are sufficient in identification of concomitant COW anomalies and how they affect outcomes. METHODS: This retrospective cohort study included adult traumatic BCVIs at 17 level I-IV trauma centers (08/01/2017-07/31/2021). The objectives were to compare screening criteria, scanning practices, and outcomes among those with and without COW anomalies. RESULTS: Of 561 BCVIs, 65% were male and the median age was 48 y/o. 17% (n = 93) had a CoW anomaly. Compared to those with normal CoW anatomy, those with CoW anomalies had significantly higher rates of any strokes (10% vs. 4%, p = 0.04), ICHs (38% vs. 21%, p = 0.001), and clinically significant bleed (CSB) before antithrombotic initiation (14% vs. 3%, p < 0.0001), respectively. Compared to patients with a normal CoW, those with a CoW anomaly also had ischemic strokes more often after antithrombotic interruption (13% vs. 2%, p = 0.02).Patients with CoW anomalies were screened significantly more often because of some other head/neck indication not outlined in BCVI screening criteria than patients with normal CoW anatomy (27% vs. 18%, p = 0.04), respectively. Scans identifying CoW anomalies included both the head and neck significantly more often (53% vs. 29%, p = 0.0001) than scans identifying normal CoW anatomy, respectively. CONCLUSIONS: While previous studies suggested universal scanning for BCVI detection, this study found patients with BCVI and CoW anomalies had some other head/neck injury not identified as BCVI scanning criteria significantly more than patients with normal CoW which may suggest that BCVI screening across all patients with a head/neck injury may improve the simultaneous detection of CoW and BCVIs. When screening for BCVI, scans including both the head and neck are superior to a single region in detection of concomitant CoW anomalies. Worsened outcomes (strokes, ICH, and clinically significant bleeding before antithrombotic initiation) were observed for patients with CoW anomalies when compared to those with a normal CoW. Those with a CoW anomaly experienced strokes at a higher rate than patients with normal CoW anatomy specifically when antithrombotic therapy was interrupted. This emphasizes the need for stringent antithrombotic therapy regimens among patients with CoW anomalies and may suggest that patients CoW anomalies would benefit from more varying treatment, highlighting the need to include the CoW anatomy when scanning for BCVI. LEVEL OF EVIDENCE: Level III, Prognostic/Epidemiological.


Asunto(s)
Traumatismos Cerebrovasculares , Círculo Arterial Cerebral , Heridas no Penetrantes , Humanos , Círculo Arterial Cerebral/anomalías , Círculo Arterial Cerebral/anatomía & histología , Círculo Arterial Cerebral/diagnóstico por imagen , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Traumatismos Cerebrovasculares/diagnóstico por imagen , Heridas no Penetrantes/complicaciones , Adulto , Centros Traumatológicos
2.
Trauma Surg Acute Care Open ; 8(1): e001094, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37342819

RESUMEN

Objective: Operative management of axis fractures (C2) usually depend on the stability and location of the break and individual patient characteristics. We sought to describe the epidemiology of C2 fractures and hypothesized that determinants for surgery would differ by fracture diagnosis. Methods: Patients with C2 fractures were identified from the US National Trauma Data Bank from January 1, 2017, to January 1, 2020. Patients were classified by C2 fracture diagnosis: odontoid type II, odontoid types I and III, and non-odontoid fracture (hangman's fracture or fractures through base of the axis). The primary comparison was C2 fracture surgery versus non-operative management. Multivariate logistic regression was used to identify independent associations with surgery. Decision tree-based models were developed to identify determinants for surgery. Results: There were 38 080 patients; 42.7% had an odontoid type II fracture; 16.5% had an odontoid type I/III fracture; and 40.8% had a non-odontoid fracture. All examined patient demographics, clinical characteristics, outcomes, and interventions differed by C2 fracture diagnosis. Overall, 5292 (13.9%) were surgically managed (17.5% odontoid type II, 11.0% odontoid type I/III, and 11.2% non-odontoid; p<0.001). The following covariates increased odds of surgery for all three fracture diagnoses: younger age, treatment at a level I trauma center, fracture displacement, cervical ligament sprain, and cervical subluxation. Determinants of surgery differed by fracture diagnosis: for odontoid type II, age ≤80 years, a displaced fracture, and cervical ligament sprain were determinants; for odontoid type I/III, age ≤85 years, a displaced fracture, and cervical subluxation were determinants; for non-odontoid fractures, cervical subluxation and cervical ligament sprain were the strongest determinants for surgery, by hierarchy. Conclusions: This is the largest published study of C2 fractures and current surgical management in the USA. Odontoid fractures, regardless of type, had age and fracture displacement as the strongest determinants for surgical management, whereas associated injuries were determinants of surgery for non-odontoid fractures. Level of evidence: III.

3.
J Am Geriatr Soc ; 71(2): 516-527, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36330687

RESUMEN

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability in older adults. The aim of this study was to characterize the burden of TBI in older adults by describing demographics, care location, diagnoses, outcomes, and payments in this high-risk group. METHODS: Using 2016-2019 Centers for Medicare & Medicaid Services (CMS) Inpatient Standard Analytical Files (IPSAF), patients >65 years with TBI (>1 injury ICD-10 starting with "S06") were selected. Trauma center levels were linked to the IPSAF file via American Hospital Association Hospital Provider ID and fuzzy-string matching. Patient variables were compared across trauma center levels. RESULTS: Three hundred forty-eight thousand eight hundred inpatients (50.4% female; 87.1% white) from 2963 US hospitals were included. Level I/II trauma centers treated 66.9% of patients; non-trauma centers treated 21.5%. Overall inter-facility transfer rate was 19.2%; in Level I/II trauma centers transfers-in represented 23.3% of admissions. Significant TBI (Head AIS ≥3) was present in 70.0%. Most frequent diagnoses were subdural hemorrhage (56.6%) and subarachnoid hemorrhage (30.6%). Neurosurgical operations were performed in 10.9% of patients and operative rates were similar regardless of center level. Total unadjusted mortality for the sample was 13.9%, with a mortality of 8.1% for those who expired in-hospital, and an additional 5.8% for those discharged to hospice. Medicare payments totaled $4.91B, with the majority (73.4%) going to Level I/II trauma centers. CONCLUSIONS: This study fills a gap in TBI research by demonstrating that although the majority of older adult TBI patients in the United States receive care at Level I/II trauma centers, a substantial percentage are managed at other facilities, despite 1 in 10 requiring neurosurgical operation regardless of level of trauma center. This analysis provides preliminary data on the function of regionalized trauma care for older adult TBI care. Future studies assessing the efficacy of early care guidelines in this population are warranted.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Pacientes Internos , Humanos , Femenino , Anciano , Estados Unidos/epidemiología , Masculino , Medicare , Lesiones Traumáticas del Encéfalo/epidemiología , Lesiones Traumáticas del Encéfalo/terapia , Hospitalización , Alta del Paciente , Estudios Retrospectivos
4.
Biomedicines ; 12(1)2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38255181

RESUMEN

Myoendothelial junctions (MEJs) are structures that allow chemical signals to be transmitted between endothelial cells (ECs) and vascular smooth muscle cells, which control vascular tone. MEJs contain hemoglobin alpha (Hbα) and endothelial nitric oxide synthase (eNOS) complexes that appear to control the production and scavenging of nitric oxide (NO) along with the activity of cytochrome b5 reductase 3 (CYB5R3). The aim of this study was to examine how hypoxia affected the regulation of proteins involved in the production of NO in brain ECs. In brief, human brain microvascular endothelial cells (HBMEC) were exposed to cobalt chloride (CoCl2), a hypoxia mimetic, and a transcriptional analysis was performed using primers for eNOS, CYB5R3, and Hbα2 with ΔΔCt relative gene expression normalized to GAPDH. NO production was also measured after treatment using 4,5-diaminofluorescein diacetate (DAF-DA), a fluorescent NO indicator. When HBMEC were exposed to CoCl2 for 48 h, eNOS and CYB5R3 messenger RNA significantly decreased (up to -17.8 ± 4.30-fold and -10.4 ± 2.8, respectively) while Hbα2 increased to detectable levels. Furthermore, CoCl2 treatment caused a redistribution of peripheral membrane-generated NO production to a perinuclear region. To the best of our knowledge, this is the first time this axis has been studied in brain ECs and these findings imply that hypoxia may cause dysregulation of proteins that regulate NO production in brain MEJs.

5.
Rev Med Chil ; 149(5): 682-688, 2021 May.
Artículo en Español | MEDLINE | ID: mdl-34751320

RESUMEN

BACKGROUND: Loxoscelism is an important public health problem in Chile and South America, due to the higher rate of cutaneous-visceral involvement. The diagnosis of loxoscelism is mostly clinical without established diagnostic criteria. There is little evidence to support any treatment used in this condition. AIM: To characterize the clinical features and epidemiology of loxoscelism among patients consulting at the Emergency and Dermatology Services of a clinical hospital between 2013 and 2017. MATERIAL AND METHODS: Review of medical records of patients registered in the electronic clinical record system with a confirmed diagnosis of loxoscelism. Epidemiological, clinical, laboratory tests and treatment variables were analyzed. RESULTS: We reviewed data from 200 patients. Ninety-four percent presented cutaneous loxoscelism and 5.5% cutaneous-visceral loxoscelism. Systemic symptoms were present in 73% of patients with cutaneous-visceral loxoscelism. Patients who developed systemic symptoms had an 18 times higher risk of developing cutaneous-visceral loxoscelism. Laboratory abnormalities were more common in patients with cutaneous-visceral loxoscelism. Not all patients with hematuria had cutaneous-visceral loxoscelism. Most patients required analgesia. Anti-loxosceles serum was not used in any patient. CONCLUSIONS: Many questions remain to be answered regarding the diagnosis and treatment of the disease. Studies are required to validate diagnostic criteria for loxoscelism, predictors for visceral involvement and response to treatment.


Asunto(s)
Picaduras de Arañas , Venenos de Araña , Arañas , Animales , Chile/epidemiología , Humanos , Dolor , Picaduras de Arañas/diagnóstico , Picaduras de Arañas/epidemiología , Picaduras de Arañas/terapia
6.
Kans J Med ; 14: 163-169, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34262636

RESUMEN

INTRODUCTION: Few randomized controlled studies have been conducted comparing a small to large fascial bite technique, yet recommendations have been made to standardize small bite closures. However, large scale randomized controlled trials require considerable effort and may benefit from a pilot study. METHODS: This multi-center randomized controlled pilot study of adult patients undergoing median laparotomy incision investigated the feasibility of studying the outcomes between small and large surgical closure techniques. RESULTS: Fifty of 100 planned patients consented, 32 patients completed surgery, and 19 patients completed the one-year ultrasound. Enrollment was 2.7 versus 8 patients per month pre/post addition of a study coordinator. Clinical results are summarized for feasibility demonstration purposes, but not analyzed for hypothesis testing. The total cost of the pilot study was $19,152.50 and took 22 months from first surgery to final one-year ultrasound. CONCLUSIONS: This feasibility assessment demonstrated the complexity of planning a large-scale randomized trial evaluating small and large bite surgical closure technique. To expand this pilot study to a full scaled sample size study would require dedicated personnel and large grant funding.

7.
Rev. méd. Chile ; 149(5): 682-688, mayo 2021. tab
Artículo en Español | LILACS | ID: biblio-1389519

RESUMEN

Background: Loxoscelism is an important public health problem in Chile and South America, due to the higher rate of cutaneous-visceral involvement. The diagnosis of loxoscelism is mostly clinical without established diagnostic criteria. There is little evidence to support any treatment used in this condition. Aim: To characterize the clinical features and epidemiology of loxoscelism among patients consulting at the Emergency and Dermatology Services of a clinical hospital between 2013 and 2017. Material and Methods: Review of medical records of patients registered in the electronic clinical record system with a confirmed diagnosis of loxoscelism. Epidemiological, clinical, laboratory tests and treatment variables were analyzed. Results: We reviewed data from 200 patients. Ninety-four percent presented cutaneous loxoscelism and 5.5% cutaneous-visceral loxoscelism. Systemic symptoms were present in 73% of patients with cutaneous-visceral loxoscelism. Patients who developed systemic symptoms had an 18 times higher risk of developing cutaneous-visceral loxoscelism. Laboratory abnormalities were more common in patients with cutaneous-visceral loxoscelism. Not all patients with hematuria had cutaneous-visceral loxoscelism. Most patients required analgesia. Anti-loxosceles serum was not used in any patient. Conclusions: Many questions remain to be answered regarding the diagnosis and treatment of the disease. Studies are required to validate diagnostic criteria for loxoscelism, predictors for visceral involvement and response to treatment.


Asunto(s)
Humanos , Animales , Picaduras de Arañas/diagnóstico , Picaduras de Arañas/terapia , Picaduras de Arañas/epidemiología , Venenos de Araña , Arañas , Dolor , Chile/epidemiología
8.
Trauma Surg Acute Care Open ; 6(1): e000642, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33634213

RESUMEN

BACKGROUND: Reports indicate social distancing guidelines and other effects of the COVID-19 pandemic impacted trauma patient volumes and injury patterns. This report is the first analysis of a large trauma network describing the extent of these impacts. The objective of this study was to describe the effects of the COVID-19 pandemic on patient volumes, demographics, injury characteristics, and outcomes. METHODS: For this descriptive, multicenter study from a large, multistate hospital network, data were collected from the system-wide centralized trauma registry and retrospectively reviewed to retrieve patient information including volume, demographics, and outcomes. For comparison, patient data from January through May of 2020 and January through May of 2019 were extracted. RESULTS: A total of 12 395 trauma patients (56% men, 79% white, mean age 59 years) from 85 trauma centers were included. The first 5 months of 2020 revealed a substantial decrease in volume, which began in February and continued into June. Further analysis revealed an absolute decrease of 32.5% in patient volume in April 2020 compared with April 2019 (4997 from 7398; p<0.0001). Motor vehicle collisions decreased 49.7% (628 from 1249). There was a statistically significant increase in injury severity score (9.0 vs. 8.3; p<0.001). As a proportion of the total trauma population, blunt injuries decreased 3.1% (87.3 from 90.5) and penetrating injuries increased 2.7% (10.0 from 7.3; p<0.001). A significant increase was found in the proportion of patients who did not survive to discharge (3.6% vs. 2.8%; p=0.010; absolute decrease: 181 from 207). DISCUSSION: Early phases of the COVID-19 pandemic were associated with a 32.5% decrease in trauma patient volumes and altered injury patterns at 85 trauma centers in a multistate system. This preliminary observational study describes the initial impact of the COVID-19 pandemic and warrants further investigation. LEVEL OF EVIDENCE: Level II (therapeutic/care management).

9.
J Stroke Cerebrovasc Dis ; 29(6): 104804, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32305279

RESUMEN

BACKGROUND: Blunt cerebrovascular injuries (BCVIs) are associated with long-term neurological effects. The first-line treatment for BCVIs is antithrombotics, but consensus on the optimal choice and timing of treatment is lacking. METHODS: This was a retrospective study on patients aged at least 18 years admitted to 6 level 1 trauma centers between 1/1/2014 and 12/31/2017 with grade 1-4 BCVI and treated with antithrombotics. Differences in treatment practices were examined across the 6 centers. The primary outcome was ischemic stroke, and secondary outcomes were related to bleeding complications: blood transfusion and intracranial hemorrhage (ICH). Treatment characteristics examined were time to diagnosis and first computerized tomography angiography, time of total treatment course, time on each antithrombotic (anticoagulants, antiplatelets, combination), time from hospital arrival to antithrombotic initiation, and treatment interruption, i.e., treatment halted for a surgical procedure and restarted postoperatively. Chi-square, Fisher exact, Spearman's rank-order correlation, Wilcoxon rank-sum, Kruskal-Wallis, and Cox proportional hazards models with time-varying covariates were used to evaluate associations with the outcomes. RESULTS: A total of 189 patients with BCVI were included. The median (IQR) time from arrival to antithrombotic initiation was 27 (8-61) hours, and 28% of patients had treatment interrupted. The ischemic stroke rate was 7.5% (n = 14), with most strokes (64%, n = 9) occurring between arrival and treatment initiation. Treatment interruption was associated with ischemic stroke (75% of patients with stroke had an interruption versus 24% of patients with no stroke; P < .01). Time on anticoagulants was not associated with ischemic stroke (P = .78), transfusion (P = .43), or ICH (P = .96). Similarly, time on antiplatelets (P = .54, P = .65, P = .60) and time on combination therapy (P = .96, P = .38, P = .57) were not associated with these outcomes. CONCLUSIONS: The timing and consistency of antithrombotic administration are critical in preventing adverse outcomes in patients with BCVI. Most ischemic strokes in this study population occurred between arrival and antithrombotic initiation, representing events that may potentially be intervened upon by earlier treatment. Future studies should examine the safety of continuing treatment through surgical procedures.


Asunto(s)
Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Isquemia Encefálica/etiología , Hemorragia Cerebral Traumática/etiología , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular/etiología , Heridas no Penetrantes/tratamiento farmacológico , Adulto , Transfusión Sanguínea , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/etiología , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/terapia , Hemorragia Cerebral Traumática/diagnóstico por imagen , Hemorragia Cerebral Traumática/terapia , Esquema de Medicación , Femenino , Fibrinolíticos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Factores de Tiempo , Tiempo de Tratamiento , Resultado del Tratamiento , Estados Unidos , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/etiología
10.
Clin Chim Acta ; 499: 70-74, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31479652

RESUMEN

BACKGROUND: Commercial solutions of human serum albumin (HSA) are administered to critically ill patients for the treatment of shock, restoration of blood volume, and the acute management of burns. Previously, conflicting results on the effects of HSA administration have been reported varying from a favorable increase in total plasma antioxidant capacity to a higher mortality rate in traumatic brain injury (TBI) patients. These results could be partially explained due to the known heterogeneity of HSA solutions. We report the discovery of S-sulfonated human transthyretin (hTTR) in HSA solutions. METHODS: Proteomics was performed on commercially available solutions of 5% HSA by LC-MS analysis. The MS charge envelope for hTTR was deconvolved to the uncharged native hTTR parent mass (13,762 Da). The parent mass was then integrated, and relative proportions of the 2 major species of hTTR, native and S-sulfonated hTTR (13,842 Da), were calculated. RESULTS: The majority of hTTR found in 5% commercial HSA solutions is in the S-sulfonated form regardless of the age of the HSA solution. S-sulfonation of hTTR at the free cysteine residue in position 10 appears to be the result of a mixed disulfide exchange possibly with S-cysteinylated hTTR or S-cysteinylated HSA. hTTR is a tetramer composed of four identical monomers each containing a reduced cysteine residue in position 10. S-sulfonation of hTTR at this cysteine residue can destabilize the hTTR tetramer, an important step in the formation of TTR-related amyloid fibrils. CONCLUSIONS: Administration of a commercial HSA solution that already contains S-sulfonated hTTR could potentially contribute to the development of amyloid-related/polyneuropathy in the critically ill.


Asunto(s)
Neuropatías Amiloides/metabolismo , Prealbúmina/análisis , Albúmina Sérica Humana/química , Soluciones/química , Soluciones/economía , Neuropatías Amiloides/patología , Cromatografía Liquida , Cisteína/química , Cisteína/metabolismo , Humanos , Espectrometría de Masas , Oxidación-Reducción , Prealbúmina/metabolismo , Proteómica , Albúmina Sérica Humana/metabolismo
11.
Trauma Surg Acute Care Open ; 4(1): e000323, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31392280

RESUMEN

BACKGROUND: We sought to identify predictors of splenic artery embolization (SAE) over observation for hemodynamically stable patients with blunt splenic injury (BSI), by Organ Injury Scale (OIS) grade. METHODS: This was a multi-institutional retrospective study of all adults (≥18) with BSI who were initially managed non-operatively between 2014 and 2016. Multivariate logistic regression analysis was used to identify predictors of SAE by OIS grade. Covariates included radiographic characteristics (presence/quantity of hemoperitoneum, blush, vascular injury), demographics (age, sex, cause), Injury Severity Score, vital signs, and hemoglobin values. We also examined outcomes of death, length of stay (LOS), intensive care unit (ICU) admission, blood products, and failed non-operative management (NOM). RESULTS: Among 422 patients with stable BSI, 93 (22%) had SAE and 329 (78%) were observed. The rate of SAE increased by grade (p<0.001). In grade I and II BSI, 7% had SAE; significant predictors of SAE were blush (OR: 5.9, p=0.02), moderate or large hemoperitoneum (OR: 3.0, p=0.01), and male sex (OR: 6.3, p=0.05). In grade III BSI, 26% had SAE; significant predictors included moderate or large hemoperitoneum (OR: 3.9, p=0.04), motor vehicle crash (OR: 6.1, p=0.005), and age (OR=1.4, 40% with each decade increase in age, p=0.02). The rate of SAE was 52% for grade IV and 85% for grade V BSI; there were no independent predictors of SAE in either grade. Clinical outcomes were comparable by NOM strategy and grade, except longer LOS with SAE in grades I-III (p<0.05) and longer ICU LOS with SAE in grades I-IV (p<0.05). Only 5 (1.2%) patients failed NOM (4 observation, 1 SAE). CONCLUSION: These results strongly support SAE consideration for patients with stable grade IV and V BSI even if there are no other high-risk clinical or radiographic findings. For grades I-III, the identified predictors may help refine consideration for SAE. LEVEL OF EVIDENCE: Level III, retrospective epidemiological study.

12.
Front Med (Lausanne) ; 6: 54, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30972338

RESUMEN

Severe sepsis, systemic inflammatory response syndrome (SIRS), and traumatic brain injury are frequently associated with hyperglycemia in non-diabetic patients. In patients suffering from any of these conditions, hyperglycemia at admission to an intensive care unit (ICU) is directly correlated with increased mortality or morbidity. Although there was initial enthusiasm for insulin treatment to blood glucose levels below 110 mg/dL in these patients, recent understanding suggests that the potential for hypoglycemic complications make this approach potentially dangerous. More moderate glucose control seems to be more beneficial than the aggressive glucose lowering initially suggested. An important publication has shown that hyperlactatemia accompanying hyperglycemia could be the real culprit in bad outcomes. This suggests that coupling moderate glucose lowering with therapeutic agents which might treat the underlying metabolic disturbances in these conditions may be a better strategy. The key metabolic disturbance in these three conditions seems to be persistent glycolysis as an energy source even in the presence of adequate tissue oxygenation (the Warburg Effect). We look at recent advances in understanding aerobic glycolysis and possibly the action of DPP4 on incretins resulting in insulin dysregulation and suggest key metabolic pathways involved in hyperglycemia regulation.

13.
Clin Exp Rheumatol ; 36(5): 891-895, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30272545

RESUMEN

OBJECTIVES: Traumatic joint injury induces chondrocyte dysfunction and progressive breakdown of articular cartilage, leading to post-traumatic osteoarthritis (PTOA). In this condition, dysfunctional fibroblast-like chondrocytes (FLCs) no longer express proteins required for cartilage maintenance, such as SOX9 and collagen-type II (COL2). Interleukin-6 (IL-6) has been demonstrated to downregulate expression of these two critical proteins in chondrocytes, and increased IL-6 levels have been measured in patients with PTOA. The <5kDa fraction of human serum albumin (LMWF5A) has been suggested to modulate this pathway, as decreased levels of IL-6 are secreted by immunostimulated LMWF5A-treated macrophages. Our objective was to determine whether LMWF5A induces an in vitro model of FLCs to redifferentiate into functional chondrocytes. METHODS: SOX9 and COL2 were monitored via western blot, and COL2 was detected with immunofluorescence. Aggrecan and IL-6 were quantified by ELISA. Glycosaminoglycan (GAG) levels were quantified with alcian blue. RESULTS: We found that LMWF5A significantly increases the principal cartilage transcription factor SOX9 and the SOX9 target protein COL2 in monolayer-cultured FLCs. Multiple LMWF5A treatments of 3-D pellet FLC cultures over 2wks resulted in a significant decrease in IL-6 and significant increases in the major players of articular cartilage mechanics, aggrecan and highly-sulfated GAGs. CONCLUSIONS: These data support the hypothesis and clinical outcomes of two phase III clinical trials that LMWF5A-treatment induces chondrogenesis and supports functional cartilage. We propose that LMWF5A could maintain articular cartilage integrity in all joints following traumatic injury.


Asunto(s)
Transdiferenciación Celular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Condrogénesis/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Osteoartritis/tratamiento farmacológico , Albúmina Sérica Humana/farmacología , Agrecanos/metabolismo , Células Cultivadas , Condrocitos/metabolismo , Condrocitos/patología , Colágeno Tipo II/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Glicosaminoglicanos/metabolismo , Humanos , Interleucina-6/metabolismo , Peso Molecular , Osteoartritis/metabolismo , Osteoartritis/patología , Fenotipo , Factor de Transcripción SOX9/metabolismo
14.
Biochem Biophys Rep ; 15: 61-67, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30073204

RESUMEN

After a traumatic insult, macrophages can become activated leading to general inflammation at the site of injury. Activated macrophages are partially regulated by the aryl hydrocarbon receptor (AhR) which when activated suppresses inflammation by limiting the secretion of pro-inflammatory cytokines and promoting the over expression of immuno-modulatory mediators. This study aims to determine whether the low molecular weight fraction of 5% human serum albumin (LMWF5A) and N-acetyl kynurenine (NAK), an N-acetyl tryptophan (NAT) breakdown product in LMWF5A, can regulate inflammation by inhibiting macrophage activation through the AhR since kynurenine is a known AhR agonist. Using LCMS, we demonstrate that NAT is non-enzymatically degraded during accelerated aging of LMWF5A with high heat accelerating degradation. More importantly, NAK is a major degradation product found in LMWF5A. THP-1 monocytes were differentiated into macrophages using phorbol 12-myristate 13-acetate (PMA) and pre-treated with 2-fold dilutions of LMWF5A or synthetic NAK with or without an AhR antagonist (CH223191) prior to overnight stimulation with lipopolysaccharide (LPS). Treatment with LMWF5A caused a 50-70% decrease in IL-6 release throughout the dilution series. A dose-response inhibition of IL-6 release was observed for NAK with maximal inhibition (50%) seen at the highest NAK concentration. Finally, an AhR antagonist partially blocked the anti-inflammatory effect of LMWF5A while completely blocking the effect of NAK. A similar inhibitory effect was observed for CXCL-10, but the AhR antagonist was not effective suggesting additional mechanisms for CXCL-10 release. These preliminary findings suggest that LMWF5A and NAK partially promote the suppression of activated macrophages via the AhR receptor. Therefore, LMWF5A, which contains NAK, is potentially a useful therapeutic in medical conditions where inflammation is prevalent such as trauma, sepsis, and wound healing.

15.
Clin Chim Acta ; 482: 149-154, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29627488

RESUMEN

Within the first few hours of a traumatic brain injury, the activity of extracellular matrix degradative enzymes increases. As a result, the blood brain barrier becomes disrupted as secondary white matter injury increases. Anoikis, a form of apoptosis, results from cells detaching from the extracellular matrix leading to cell death. This "homelessness" (anoikis) of cells hinders recovery progression, exacerbating brain injury while disrupting synaptic plasticity and other central nervous system functions. Here, we discuss the current knowledge of molecular pathways and proteins involved in both the activation and inhibition of anoikis.


Asunto(s)
Anoicis , Lesiones Traumáticas del Encéfalo/patología , Caspasas , Muerte Celular , Matriz Extracelular , Humanos , Cicatrización de Heridas
16.
Rev. méd. Chile ; 145(10): 1308-1311, oct. 2017. tab, graf
Artículo en Español | LILACS | ID: biblio-1043139

RESUMEN

Background: The incidence of out of hospital cardiac arrest (OHCA) is approximately 20 to 140 per 100.000 inhabitants. International registries, based on Utstein criteria have allowed standardized reporting of OHCA profiles and outcomes in different countries. We proposed to create a local OHCA registry. Aim: To assess the quality of the information about OHCA currently recorded in medical records according to Utstein guidelines. Material and Methods: A retrospective analysis of medical records of patients arriving in the emergency room of a public hospital with OHCA during a 3-year period. Data regarding the patient characteristics, event and outcomes were analyzed. Results: During the revision period, 317 patients arrived with an OHCA. None of the medical records had complete data on items that are considered a minimum requirement by Utstein guidelines. Mean age of patients was 63 years old, 60% were men, the most common arrest rhythm was asystole (43%) and 8% of patients were discharged alive. Conclusions: Data recorded in medical records is insufficient to inform the profile of OHCA. A prospective registry is currently being implemented based on the information provided by this study. This registry should optimize reporting and data analysis.


Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Hospitales Urbanos/estadística & datos numéricos , Registros Médicos/normas , Paro Cardíaco Extrahospitalario/mortalidad , Hospitales Públicos/estadística & datos numéricos , Chile , Tasa de Supervivencia , Estudios Retrospectivos , Servicios Médicos de Urgencia/estadística & datos numéricos , Control de Formularios y Registros/métodos
18.
Am J Crit Care ; 25(4): 327-34, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27369031

RESUMEN

BACKGROUND: Allocating resources appropriately requires knowing whether obese patients use more resources during a hospital stay than nonobese patients. OBJECTIVES: To determine if trauma patients with different body mass indexes differed in use of resources measured as a multifaceted outcome variable. METHODS: A trauma registry was used for a retrospective study of adult patients admitted to a midwestern level I trauma center. Patients were stratified into 3 groups: nonobese (normal weight, overweight), obese, and morbidly obese. Three canonical correlation analyses were used to determine the relationship between patient/injury characteristics and hospital resource usage. RESULTS: In a sample of 9771 patients, 71.2% were non-obese, 23.8% obese, and 5.0% morbidly obese. For patient/injury characteristics, Injury Severity Score and physiological complications were significant variables for all 3 groups. Scores on the Glasgow Coma Scale were significant for nonobese patients only. For resource usage, intensive care unit length of stay and procedures were significant variables for all 3 groups. CONCLUSIONS: Associations between body mass index and outcomes have been noted when assessed as independent variables. However, when resource usage was assessed as a multifaceted outcome variable, injury factors (higher Injury Severity Score, lower scores on the Glasgow Coma Scale, more physiological complications) were associated with resource usage (increased length of stay in the intensive care unit and increased number of procedures). These findings provide clinicians a new perspective for evaluating the complex relationship between patient/injury characteristics and hospital resource usage.


Asunto(s)
Índice de Masa Corporal , Recursos en Salud/estadística & datos numéricos , Puntaje de Gravedad del Traumatismo , Obesidad/epidemiología , Complicaciones Posoperatorias/epidemiología , Heridas y Lesiones/epidemiología , Comorbilidad , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Medio Oeste de Estados Unidos/epidemiología , Estudios Retrospectivos , Centros Traumatológicos/estadística & datos numéricos , Heridas y Lesiones/terapia
19.
J Trauma Nurs ; 21(5): 201-8, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25198073

RESUMEN

Postresuscitation debriefings allow team members to reflect on performance and discuss areas for improvement. Pre-/postsurveys of trauma team members (physicians, mid-level practitioners, technicians, pharmacists, and nurses) were administered to evaluate the acceptability of debriefings and self-perceptions after multidisciplinary trauma resuscitations. After a 3-month trial period, improvements were observed in perceptions of psychological and patient safety, role on team, team communication, and acceptability of the debriefing initiative. Regrouping for a debriefing requires organizational change, which may be more easily assimilated if team members recognize the potential for process improvement and feel confident about success.


Asunto(s)
Competencia Clínica , Comunicación Interdisciplinaria , Grupo de Atención al Paciente/organización & administración , Resucitación/métodos , Heridas y Lesiones/terapia , Adulto , Enfermedad Crítica/enfermería , Enfermedad Crítica/terapia , Enfermería de Urgencia/organización & administración , Femenino , Encuestas de Atención de la Salud , Humanos , Masculino , Persona de Mediana Edad , Mejoramiento de la Calidad , Encuestas y Cuestionarios , Heridas y Lesiones/diagnóstico
20.
JAAPA ; 27(2): 1-8, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24463744

RESUMEN

OBJECTIVES: Compare and assess information available on the Internet about the definition, symptoms, treatment, and return to play recommendations after a concussion. METHODS: The top 10 websites generated by a Google search on the keyword "concussion" were evaluated by two independent researchers and three medical professionals for definition, signs, symptoms, home treatment, care-seeking advice, and return to play recommendations. The medical professionals also rated their willingness to recommend each website to patients. RESULTS: Each website contained a general list of signs, symptoms, and home treatment. One website advised the use of ibuprofen, four advised against ibuprofen, and five made no medication recommendations. Nine websites contained guidance on seeking physician care, and eight recommended athletes not return to play until cleared by a healthcare professional. CONCLUSION: Nine of the websites contained information for each section evaluated; however, information was inconsistent. Healthcare providers should be aware of the variable quality of information available on the Internet and guide patients to more optimal resources.


Asunto(s)
Conmoción Encefálica , Sistemas en Línea , Humanos
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