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INTRODUCTION: Although low-energy pelvic fractures seldom present with significant hemorrhage, early recognition of at-risk patients is essential. We aimed to identify predictors of transfusion requirements in this cohort. METHODS: A 7-y retrospective chart review was performed. Low-energy mechanism was defined as falls of ≤5 feet. Fracture pattern was classified using the Orthopedic Trauma Association/Arbeitsgemeinschaft für Osteosynthesefragen system as A, B, or C. Primary outcome was transfusion of ≥2 units of packed red blood cells in the first 48 h. Univariable analysis and logistic regression analysis were performed. A P value ≤0.05 was considered significant. RESULTS: Five hundred forty six patients were included with median (interquartile range) age of 86 (79-91) and median (interquartile range) Injury Severity Score of 5 (4-8). Five hundred forty one (99%) had type A fractures. Twenty six (5%) had the primary outcome and 17 (3%) died. Logistic regression found that systolic blood pressure <100 mmHg at any time in the Emergency Department, Injury Severity Score, and pelvic angiography were predictors of the primary outcome. Seventeen percent of those who had the primary outcome died compared with 2% who did not (P = 0.0004). Three hundred sixty four (67%) received intravenous contrast for computerized tomography scans and of these, 44 (12%) had contrast extravasation (CE). CE was associated with the primary outcome but not mortality. CONCLUSIONS: Hypotension at any time in the Emergency Department and CE on computerized tomography predicted transfusion of ≥2 units packed red blood cells in the first 48 h in patients with low-energy pelvic fractures.
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Fraturas Ósseas , Hipotensão , Ossos Pélvicos , Humanos , Estudos Retrospectivos , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/lesões , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/terapia , Fraturas Ósseas/complicações , Hipotensão/etiologia , Extravasamento de Materiais Terapêuticos e Diagnósticos/diagnóstico por imagem , Extravasamento de Materiais Terapêuticos e Diagnósticos/epidemiologia , Extravasamento de Materiais Terapêuticos e Diagnósticos/etiologia , Serviço Hospitalar de Emergência , Escala de Gravidade do Ferimento , Transfusão de Sangue , TomografiaRESUMO
INTRODUCTION: The obesity epidemic plagues the United States, affecting approximately 42% of the population. The relationship of obesity with injury severity and outcomes has been poorly studied among motorcycle collisions (MCC). This study aimed to compare injury severity, mortality, injury regions, and hospital and intensive care unit length of stay (LOS) between obese and normal-weight MCC patients. METHODS: Trauma registries from three Pennsylvania Level 1 trauma centers were queried for adult MCC patients (January 1, 2016, and December 31, 2020). Obesity was defined as adult patients with body mass index ≥ 30 kg/m2 and normal weight was defined as body mass index < 30 kg/m2 but > 18.5 kg/m2. Demographics and injury characteristics including injury severity score (ISS), abbreviated injury score, mortality, transfusions and LOS were compared. P ≤ 0.05 was considered significant. RESULTS: One thousand one hundred sixty-four patients met the inclusion criteria: 40% obese (n = 463) and 60% nonobese (n = 701). Comparison of ISS demonstrated no statistically significant difference between obese and normal-weight patients with median ISS (interquartile range) 9 (5-14) versus 9 (5-14), respectively (P = 0.29). Obese patients were older with median age 45 (32-55) y versus 38 (26-54) y, respectively (P < 0.01). Comorbidities were equally distributed among both groups except for the incidence of hypertension (30 versus 13.8%, P < 0.01) and diabetes (11 versus 4.4%, P < 0.01). There was no statistically significant difference in Trauma Injury Severity Score or abbreviated injury score. Hospital LOS, intensive care unit LOS, and 30-day mortality among both groups were similar. CONCLUSIONS: Obese patients experiencing MCC had no differences in distribution of injury, mortality, or injury severity, mortality, injury regions, and hospital compared to normal-weight adults. Our study differs from current data that obese motorcycle drivers may have different injury characteristics and increased LOS.
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Motocicletas , Ferimentos e Lesões , Adulto , Humanos , Estados Unidos , Pessoa de Meia-Idade , Índice de Massa Corporal , Acidentes de Trânsito , Tempo de Internação , Obesidade/complicações , Obesidade/epidemiologia , Escala de Gravidade do Ferimento , Ferimentos e Lesões/complicações , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/epidemiologia , Estudos RetrospectivosRESUMO
INTRODUCTION: Geriatric patients (GeP) often experience increased morbidity and mortality following traumatic insult and as a result, require more specialized care due to lower physiologic reserve and underlying medical comorbidities. Motorcycle injuries (MCCI) occur across all age groups; however, no large-scale studies evaluating outcomes of GeP exist for this particular subset of patients. Data thus far are limited to elderly participation in recreational activities such as water and alpine skiing, snowboarding, equestrian, snowmobiles, bicycles, and all-terrain vehicles. We hypothesized that GeP with MCCI will have a higher rate of mortality when compared with their younger counterparts despite increased helmet usage. METHODS: We performed a multicenter retrospective review of MCCI patients at three Pennsylvania level I trauma centers from January 2016 to December 2020. Data were extracted from each institution's electronic medical records and trauma registry. GeP were defined as patients aged more than or equal to 65 y. The primary outcome was mortality. Secondary outcomes included ventilator days; hospital, intensive care unit, and intermediate unit length of stays; complications; and helmet use. 3:1 nongeriatric patients (NGeP) to GeP propensity score matching (PSM) was based on sex, abbreviated injury scale (AIS), and injury severity score (ISS). P ≤ 0.05 was considered significant. RESULTS: One thousand five hundred thirty eight patients were included (GeP: 7% [n = 113]; NGP: 93% [n = 1425]). Prior to PSM, GeP had higher median Charlson Comorbidity Index (GeP: 3.0 versus NGeP: 0.0; P ≤ 0.001) and greater helmet usage (GeP: 73.5% versus NGeP: 54.6%; P = 0.001). There was a statistically significant difference between age cohorts in terms of ISS (GeP: 10.0 versus NGeP: 6.0, P = 0.43). There was no significant difference for any AIS body region. Mortality rates were similar between groups (GeP: 1.7% versus NGeP: 2.6%; P = 0.99). After PSM matching for sex, AIS, and ISS, GeP had significantly more comorbidities than NGeP (P ≤ 0.05). There was no difference in trauma bay interventions or complications between cohorts. Mortality rates were similar (GeP: 1.8% versus NGeP: 3.2%; P = 0.417). Differences in ventilator days as well as intensive care unit length of stay, intermediate unit length of stay, and hospital length of stay were negligible. Helmet usage between groups were similar (GeP: 64.5% versus NGeP: 66.8%; P = 0.649). CONCLUSIONS: After matching for sex, ISS, and AIS, age more than 65 y was not associated with increased mortality following MCCI. There was also no significant difference in helmet use between groups. Further studies are needed to investigate the effects of other potential risk factors in the aging patient, such as frailty and anticoagulation use, before any recommendations regarding management of motorcycle-related injuries in GeP can be made.
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Motocicletas , Ferimentos e Lesões , Idoso , Humanos , Pennsylvania/epidemiologia , Tempo de Internação , Centros de Traumatologia , Estudos Retrospectivos , Escala de Gravidade do Ferimento , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/terapiaRESUMO
INTRODUCTION: Neostigmine (NEO) and decompressive colonoscopy (COL) are two efficacious treatment modalities for acute colonic pseudo-obstruction (ACPO). We hypothesize that a COL first strategy is associated with better outcomes compared to a NEO first strategy. METHODS: A single-center retrospective analysis was performed from 2013 to 2020. Patients ≥18 y with a diagnosis of ACPO were included. The outcome was a composite measure of acute operative intervention, 30-day readmission with ACPO, and 30-day ACPO-related mortality. A P-value of ≤ 0.05 indicated statistical significance. RESULTS: Of 910 encounters in 849 patients, 50 (5.5%) episodes of ACPO in 39 patients were identified after exclusion of one patient with colon perforation on presentation. The median (interquartile range) age was 68 (62-84) y. NEO and COL were administered in 21 and 25 episodes, respectively. In 16 (32%) episodes, no NEO or COL was administered. When patients were given NEO first, COL or additional NEO was required in 12/18 (67%) compared with a COL first strategy where a second COL and/or NEO was given in 5/16 (32%) (P = 0.05). Both strategies had similar outcomes (NEO, 4/18 versus COL, 4/16, P = 0.85). Twenty-two (44%) episodes had an early intervention (≤48 h) with NEO and/or COL. There was no difference in outcome between those that received an early intervention and those who did not (5/22 versus 5/28, P = 0.71). CONCLUSIONS: For patients failing conservative measures, a COL first approach was associated with fewer subsequent interventions, but with similar composite outcomes compared to a NEO first approach. Early (≤48 h) intervention with NEO and/or COL was not associated with improved outcomes.
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Pseudo-Obstrução do Colo , Neostigmina , Humanos , Neostigmina/uso terapêutico , Pseudo-Obstrução do Colo/terapia , Pseudo-Obstrução do Colo/cirurgia , Estudos Retrospectivos , Colonoscopia , Resultado do Tratamento , Doença AgudaRESUMO
INTRODUCTION: The American Geriatric Society has identified polypharmacy and categories of potentially inappropriate medication (PIM) that should be avoided in the elderly. These medications can potentially cause an increased risk of falls and traumatic events. MATERIALS AND METHODS: We conducted a retrospective study on elderly patients with traumatic injuries at a Level 1 trauma center. We compared patients having only one traumatic event and those with one or more traumatic events with the presence of prescriptions for PIMs. RESULTS: Identified high risk categories of anticoagulant and antiplatelet agents (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.08-1.28), psychiatric and neurologic agents (OR 1.32, 95% CI 1.22-1.43), as well as medication with anticholinergic properties (OR 1.14, 95% CI 1.03-1.27) were associated with an increased risk of recurrent trauma. CONCLUSIONS: We can quantify the risk of recurrent trauma with certain categories of PIM. Medication reconciliation and shared decision-making regarding the continued use of these medications may positively impact trauma recidivism.
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Polimedicação , Lista de Medicamentos Potencialmente Inapropriados , Humanos , Idoso , Estudos Retrospectivos , Reconciliação de MedicamentosRESUMO
Ex vivo heart perfusion (EVHP) may facilitate resuscitation of discarded donor hearts and expand the donor pool; however, a reliable means of demonstrating organ viability prior to transplantation is required. Therefore, we sought to identify metabolic and functional parameters that predict myocardial performance during EVHP. To evaluate the parameters over a broad spectrum of organ function, we obtained hearts from 9 normal pigs and 37 donation after circulatory death pigs and perfused them ex vivo. Functional parameters obtained from a left ventricular conductance catheter, oxygen consumption, coronary vascular resistance, and lactate concentration were measured, and linear regression analyses were performed to identify which parameters best correlated with myocardial performance (cardiac index: mL·min(-1)·g(-1)). Functional parameters exhibited excellent correlation with myocardial performance and demonstrated high sensitivity and specificity for identifying hearts at risk of poor post-transplant function (ejection fraction: R(2) = 0.80, sensitivity = 1.00, specificity = 0.85; stroke work: R(2) = 0.76, sensitivity = 1.00, specificity = 0.77; minimum dP/dt: R(2) = 0.74, sensitivity = 1.00, specificity = 0.54; tau: R(2) = 0.51, sensitivity = 1.00, specificity = 0.92), whereas metabolic parameters were limited in their ability to predict myocardial performance (oxygen consumption: R(2) = 0.28; coronary vascular resistance: R(2) = 0.20; lactate concentration: R(2) = 0.02). We concluded that evaluation of functional parameters provides the best assessment of myocardial performance during EVHP, which highlights the need for an EVHP device capable of assessing the donor heart in a physiologic working mode.
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Transplante de Coração , Coração/fisiologia , Preservação de Órgãos/métodos , Perfusão/métodos , Sobrevivência de Tecidos/fisiologia , Coleta de Tecidos e Órgãos/métodos , Animais , Desenho de Equipamento , Feminino , Modelos Biológicos , Preservação de Órgãos/instrumentação , Soluções para Preservação de Órgãos , Consumo de Oxigênio/fisiologia , Perfusão/instrumentação , Sus scrofa , Coleta de Tecidos e Órgãos/instrumentaçãoRESUMO
Cardiac fibrosis accompanies a variety of myocardial disorders, and is induced by myofibroblasts. These cells may be composed of a heterogeneous population of parent cells, including interstitial fibroblasts and circulating progenitor cells. Direct comparison of human bone marrow-derived mesenchymal stem cells (BM-MSCs) and cardiac myofibroblasts (CMyfbs) has not been previously reported. We hypothesized that BM-MSCs readily adopt a myofibroblastic phenotype in culture. Human primary BM-MSCs and human CMyfbs were isolated from patients undergoing open heart surgery and expanded under standard culture conditions. We assessed and compared their phenotypic and functional characteristics by examining their gene expression profile, their ability to contract collagen gels and synthesize collagen type I. In addition, we examined the role of non-muscle myosin II (NMMII) in modulating MSC myogenic function using NMMII siRNA knockdown and blebbistatin, a specific small molecule inhibitor of NMMII. We report that, while human BM-MSCs retain pluripotency, they adopt a myofibroblastic phenotype in culture and stain positive for the myofibroblast markers α-SMA, vimentin, NMMIIB, ED-A fibronectin, and collagen type 1 at each passage. In addition, they contract collagen gels in response to TGF-ß1 and synthesize collagen similar to human CMyfbs. Moreover, inhibition of NMMII activity with blebbistatin completely attenuates gel contractility without affecting cell viability. Thus, human BM-MSCs share and exhibit similar physiological and functional characteristics as human CMyfbs in vitro, and their propensity to adopt a myofibroblast phenotype in culture may contribute to cardiac fibrosis.
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Células-Tronco Mesenquimais/metabolismo , Miocárdio/citologia , Miofibroblastos/metabolismo , Sequência de Bases , Colágeno Tipo I/biossíntese , Primers do DNA , Humanos , Técnicas In Vitro , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: Unlike large hemothoraces (HTX), small HTX after blunt trauma may be observed without drainage. We aimed to study if there were risk factors that would predict the need for intervention in initially observed small HTX. METHODS: A retrospective review of patients with blunt traumatic HTX from 2016 to 2022 was performed. Patients with small HTX (pleural fluid volume <400 mL on admission chest computerized tomography [CT]) were included. Patients were considered as being "initially observed" if there was no intervention for the HTX within 48 hours after admission. Primary outcome was any HTX-related intervention (open, thoracoscopic or percutaneous procedures) occurring after 48 hours and up to 6 months after injury. Univariable and multivariable statistical analyses were employed. A P-value of <.05 was considered significant. RESULTS: Of 335 patients with HTX, 188 (59.6%) met inclusion criteria. Median (interquartile range) HTX volume was 90 (36-134) ml. One hundred and twenty-seven (68%) were initially observed. Of these, 31 (24%) had the primary outcome. These patients had a larger HTX volume (median, 129 vs 68 mL, P = .0001), and number of rib fractures (median, 7 vs 4, P = .0002) compared to those without the primary outcome. Chest-related readmission occurred in 8 (6%) with a median of 20 days from injury. Of these, 7 required an HTX-related intervention. Logistic regression analysis found that both the number of rib fractures and HTX volume independently predicted the primary outcome. CONCLUSION: For small HTX initially observed, number of rib fractures and initial volume predicted delayed HTX-related intervention.
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Hemotórax , Ferimentos não Penetrantes , Humanos , Estudos Retrospectivos , Masculino , Feminino , Adulto , Ferimentos não Penetrantes/terapia , Ferimentos não Penetrantes/diagnóstico por imagem , Pessoa de Meia-Idade , Hemotórax/etiologia , Hemotórax/terapia , Tomografia Computadorizada por Raios X , Traumatismos Torácicos/terapia , Traumatismos Torácicos/diagnóstico por imagem , Drenagem , Fatores de Risco , Fraturas das Costelas/terapia , Fraturas das Costelas/diagnóstico por imagemRESUMO
Pennsylvania's Prescription Drug Monitoring Program (PDMP) was established in 2016, but its impact on opioid use for pelvic fractures is understudied. We compared opioid use in 277 pelvic fracture cases between two periods: 2015-2017 (T1) and 2018-2020 (T2). Outcomes included daily inpatient morphine milligram equivalents (MME), long-term opioid use (LOU) 60-90 days post-discharge, and intermediate-term opioid use (IOU) 30-60 days post-discharge. T1 and T2 had comparable baseline characteristics. T2 was associated with a decrease in average daily inpatient MME (58.6 vs 78.5, P = .02), particularly in younger patients. Regression analyses showed age and Injury Severity Score (ISS) were significant predictors for daily inpatient MME, while time period was not. Geriatric patients in T2 had significantly decreased IOU (30% vs 9%, P = .05). Pelvic fracture type and daily MME predicted IOU, while pelvic fracture type predicted LOU. This study suggests a modest impact of these laws, but further study is needed.
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Analgésicos Opioides , Fraturas Ósseas , Ossos Pélvicos , Humanos , Analgésicos Opioides/uso terapêutico , Masculino , Feminino , Pennsylvania/epidemiologia , Pessoa de Meia-Idade , Adulto , Ossos Pélvicos/lesões , Idoso , Estudos Retrospectivos , Programas de Monitoramento de Prescrição de Medicamentos/legislação & jurisprudência , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/legislação & jurisprudência , Prescrições de Medicamentos/estatística & dados numéricos , Escala de Gravidade do Ferimento , Transtornos Relacionados ao Uso de Opioides/epidemiologiaRESUMO
Cannabis-based medicines (CBMs) could help reduce systemic inflammation in people with HIV (PWH). In a prospective, randomized pilot study we enrolled participants from August 2021-April 2022 with HIV, aged ≥18 and on antiretroviral therapy and randomly assigned them to cannabidiol (CBD) ± Δ9-tetrahydrocannabinol (THC) capsules for 12 weeks with the primary objective being to assess safety and tolerability. Here we report on timeliness to study initiation, enrolment, compliance and retention rates. The target sample size was not reached. Two hundred and five individuals were approached, and 10 consented and were randomized; the rest refused (reasons: cannabis-related stigma/discomfort; too many study visits/insufficient time; unwillingness to undergo a "washout period" for three weeks) or were not eligible. The age of those randomized was 58 years (IQR 55-62); 80% were male. Only three met all criteria (30% enrolment compliance); seven were enrolled with minor protocol deviations. Compliance was excellent (100%). Eight (80%) participants completed the study; two (20%) were withdrawn for safety reasons (transaminitis and aggravation of pre-existing anemia). Time to study initiation and recruitment were the most challenging aspects. Ongoing work is required to reduce stigma related to CBMs. Future studies should find a balance between the requirements for safety monitoring and frequency of study visits.
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BACKGROUND: Despite the high incidence of blunt trauma in older adults, there is a lack of evidence-based guidance for computed tomography (CT) imaging in this population. We aimed to identify an algorithm to guide use of a Pan-Scan (Head/C-spine/Torso) or a Selective Scan (Head/C-spine ± Torso). We hypothesized that a patient's initial history and exam could be used to guide imaging. METHODS: We prospectively studied blunt trauma patients aged 65+ at 18 Level I/II trauma centers. Patients presenting >24 h after injury or who died upon arrival were excluded. We collected history and physical elements and final injury diagnoses. Injury diagnoses were categorized into CT body regions of Head/C-spine or Torso (chest, abdomen/pelvis, and T/L spine). Using machine learning and regression modeling as well as a priori clinical algorithms based, we tested various decision rules against our dataset. Our priority was to identify a simple rule which could be applied at the bedside, maximizing sensitivity (Sens) and negative predictive value (NPV) to minimize missed injuries. RESULTS: We enrolled 5,498 patients with 3,082 injuries. Nearly half (47.1%, n = 2,587) had an injury within the defined CT body regions. No rule to guide a Pan-Scan could be identified with suitable Sens/NPV for clinical use. A clinical algorithm to identify patients for Pan-Scan, using a combination of physical exam findings and specific high-risk criteria, was identified and had a Sens of 0.94 and NPV of 0.86 This rule would have identified injuries in all but 90 patients (1.6%) and would theoretically spare 11.9% (655) of blunt trauma patients a torso CT. CONCLUSIONS: Our findings advocate for Head/Cspine CT in all geriatric patients with the addition of torso CT in the setting of positive clinical findings and high-risk criteria. Prospective validation of this rule could lead to streamlined diagnostic care of this growing trauma population. LEVEL OF EVIDENCE: Level 2, Diagnostic Tests or Criteria.
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Angioembolization in blunt splenic trauma is used to maximize splenic preservation. Superiority of prophylactic embolization over expectant management in patients with a negative splenic angiography (SA) is debated. We hypothesized that embolization in negative SA would be associated with splenic salvage. Of 83 patients undergoing SA, 30 (36%) had a negative SA. Embolization was performed in 23 (77%). Grade of injury, contrast extravasation (CE) on computed tomography (CT) or embolization were not associated with splenectomy. In 20 patients with either a high-grade injury or CE on CT, 17 (85%) underwent embolization with a failure rate of 24%. In the remaining 10 without high-risk features, 6 underwent embolization with a 0% splenectomy rate. Despite embolization, the failure rate of nonoperative management (NOM) remains significant in those with high-grade injury or CE on CT. A low threshold for early splenectomy after prophylactic embolization is needed.
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Embolização Terapêutica , Ferimentos não Penetrantes , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Baço/diagnóstico por imagem , Baço/lesões , Esplenectomia , Angiografia/métodos , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/terapia , Ferimentos não Penetrantes/complicações , Extravasamento de Materiais Terapêuticos e Diagnósticos/complicações , Embolização Terapêutica/métodos , Escala de Gravidade do FerimentoRESUMO
Biosynthetic engineering of bicyclic darobactins, selectively sealing the lateral gate of the outer membrane protein BamA, leads to active analogues, which are up to 128-fold more potent against Gram-negative pathogens compared to native counterparts. Because of their excellent antibacterial activity, darobactins represent one of the most promising new antibiotic classes of the past decades. Here, we present a series of structure-driven biosynthetic modifications of our current frontrunner, darobactin 22 (D22), to investigate modifications at the understudied positions 2, 4, and 5 for their impact on bioactivity. Novel darobactins were found to be highly active against critical pathogens from the WHO priority list. Antibacterial activity data were corroborated by dissociation constants with BamA. The most active derivatives D22 and D69 were subjected to ADMET profiling, showing promising features. We further evaluated D22 and D69 for bioactivity against multidrug-resistant clinical isolates and found them to have strong activity.
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Antibacterianos , Fenilpropionatos , Antibacterianos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Higher blunt cerebrovascular injury (BCVI) grade and lack of medical therapy are associated with stroke. Knowledge of stroke risk factors specific to individual grades may help tailor BCVI therapy to specific injury characteristics. METHODS: A post-hoc analysis of a 16 center, prospective, observational trial (2018-2020) was performed including grade 1 internal carotid artery (ICA) BCVI. Repeat imaging was considered the second imaging occurrence only. RESULTS: From 145 grade 1 ICA BCVI included, 8 (5.5%) suffered a stroke. Grade 1 ICA BCVI with stroke were more commonly treated with mixed anticoagulation and antiplatelet therapy (75.0% vs 9.6%, P <.001) and less commonly antiplatelet therapy (25.0% vs 82.5%, P = .001) compared to injuries without stroke. Of the 8 grade 1 ICA BCVI with stroke, 4 (50.0%) had stroke after medical therapy was started. In comparing injuries with resolution at repeat imaging to those without, stroke occurred in 7 (15.9%) injuries without resolution and 0 (0%) injuries with resolution (P = .005). At repeat imaging in grade 1 ICA BCVI with stroke, grade of injury was grade 1 in 2 injuries, grade 2 in 3 injuries, grade 3 in 1 injury, and grade 5 in one injury. DISCUSSION: While the stroke rate for grade 1 ICA BCVI is low overall, injury persistence appears to heighten stroke risk. Some strokes occurred despite initiation of medical therapy. Repeat imaging is needed in grade 1 ICA BCVI to evaluate for injury progression or resolution.
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Lesões das Artérias Carótidas , Artéria Carótida Interna , Traumatismo Cerebrovascular , Acidente Vascular Cerebral , Artéria Carótida Interna/diagnóstico por imagem , Lesões das Artérias Carótidas/diagnóstico por imagem , Inibidores da Agregação Plaquetária , Traumatismo Cerebrovascular/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologiaRESUMO
It is believed that cardiac remodeling due to geometric and structural changes is a major mechanism for the progression of heart failure in different pathologies including hypertension, hypertrophic cardiomyopathy, dilated cardiomyopathy, diabetic cardiomyopathy, and myocardial infarction. Increases in the activities of proteolytic enzymes such as matrix metalloproteinases, calpains, cathepsins, and caspases contribute to the process of cardiac remodeling. In addition to modifying the extracellular matrix, both matrix metalloproteinases and cathepsins have been shown to affect the activities of subcellular organelles in cardiomyocytes. The activation of calpains and caspases has been identified to induce subcellular remodeling in failing hearts. Proteolytic activities associated with different proteins including caspases, calpain, and the ubiquitin-proteasome system have been shown to be involved in cardiomyocyte apoptosis, which is an integral part of cardiac remodeling. This article discusses and compares how the activities of various proteases are involved in different cardiac abnormalities with respect to alterations in apoptotic pathways, cardiac remodeling, and cardiac dysfunction. An imbalance appears to occur between the activities of some proteases and their endogenous inhibitors in various types of hypertrophied and failing hearts, and this is likely to further accentuate subcellular remodeling and cardiac dysfunction. The importance of inhibiting the activities of both extracellular and intracellular proteases specific to distinct etiologies, in attenuating cardiac remodeling and apoptosis as well as biochemical changes of subcellular organelles, in heart failure has been emphasized. It is suggested that combination therapy to inhibit different proteases may prove useful for the treatment of heart failure.
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Insuficiência Cardíaca/metabolismo , Peptídeo Hidrolases/metabolismo , Remodelação Ventricular/fisiologia , Apoptose/fisiologia , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatias Diabéticas/metabolismo , Progressão da Doença , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão/metabolismo , Metaloproteinases da Matriz/metabolismo , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismoRESUMO
It has become evident that protein degradation by proteolytic enzymes, known as proteases, is partly responsible for cardiovascular dysfunction in various types of heart disease. Both extracellular and intracellular alterations in proteolytic activities are invariably seen in heart failure associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, hypertensive cardiomyopathy, diabetic cardiomyopathy, and ischemic cardiomyopathy. Genetic cardiomyopathy displayed in different strains of hamsters provides a useful model for studying heart failure due to either cardiac hypertrophy or cardiac dilation. Alterations in the function of several myocardial organelles such as sarcolemma, sarcoplasmic reticulum, myofibrils, mitochondria, as well as extracellular matrix have been shown to be due to subcellular remodeling as a consequence of changes in gene expression and protein content in failing hearts from cardiomyopathic hamsters. In view of the increased activities of various proteases, including calpains and matrix metalloproteinases in the hearts of genetically determined hamsters, it is proposed that the activation of different proteases may also represent an important determinant of subcellular remodeling and cardiac dysfunction associated with genetic cardiomyopathy.
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Cardiomiopatias/metabolismo , Modelos Animais de Doenças , Insuficiência Cardíaca/metabolismo , Organelas/metabolismo , Peptídeo Hidrolases/metabolismo , Animais , Cardiomiopatias/genética , Cricetinae , Humanos , Modelos CardiovascularesRESUMO
BACKGROUND: As a result of the COVID-19 pandemic, providing health care while maintaining social distancing has resulted in the need to provide care remotely, support quarantined or isolated individuals, monitor infected individuals and their close contacts, as well as disseminate accurate information regarding COVID-19 to the public. This has led to an unprecedented rapid expansion of digital tools to provide digitized virtual care globally, especially mobile phone-facilitated health interventions, called mHealth. To help keep abreast of different mHealth and virtual care technologies being used internationally to facilitate patient care and public health during the COVID-19 pandemic, we carried out a rapid investigation of solutions being deployed and considered in 4 countries. OBJECTIVE: The aim of this paper was to describe mHealth and the digital and contact tracing technologies being used in the health care management of the COVID-19 pandemic among 2 high-income and 2 low-middle income countries. METHODS: We compared virtual care interventions used for COVID-19 management among 2 high-income countries (the United Kingdom and Canada) and 2 low-middle income (Kenya and Rwanda) countries. We focused on interventions used to facilitate patient care and public health. Information regarding specific virtual care technologies was procured from a variety of resources including gray literature, government and health organization websites, and coauthors' personal experiences as implementers of COVID-19 virtual care strategies. Search engine queries were performed to find health information that would be easily accessible to the general public, with keywords including "COVID-19," "contact-tracing," "tool-kit," "telehealth," and "virtual care," in conjunction with corresponding national health authorities. RESULTS: We identified a variety of technologies in Canada, the United Kingdom, Rwanda, and Kenya being used for patient care and public health. These countries are using both video and text message-based platforms to facilitate communication with health care providers (eg, WelTel and Zoom). Nationally developed contact tracing apps are provided free to the public, with most of them using Bluetooth-based technology. We identified that often multiple complimentary technologies are being utilized for different aspects of patient care and public health with the common purpose to disseminate information safely. There was a negligible difference among the types of technologies used in both high-income and low-middle income countries, although the latter implemented virtual care interventions earlier during the pandemic's first wave, which may account for their effective response. CONCLUSIONS: Virtual care and mHealth technologies have evolved rapidly as a tool for health care support for both patient care and public health. It is evident that, on an international level, a variety of mHealth and virtual care interventions, often in combination, are required to be able to address patient care and public health concerns during the COVID-19 pandemic, independent of a country's economic standing.
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Data are lacking regarding the use of diuretics in facilitating closure of the open abdomen (OA). For patients with an OA after 2 laparotomies, we hypothesized that diuretic use was associated with a higher rate of primary fascial closure than no diuretic use. A retrospective review of patients with trauma laparotomies over 7 years was performed. Primary fascial closure (PFC) was defined as apposition of fascial edges without interposition mesh. Of 321 patients, 30 (9%) remained with an OA after 2 laparotomies. Prior to the third laparotomy, median cumulative fluid balance was +12.6 L. Thirteen (43%) received diuretics. Primary fascial closure rates were similar for diuretic use vs no diuretic (38% vs 59%, P = .46). Primary fascial closure was not associated with age (P = .2), gender (P = 0.7), cumulative fluid balance (P = .3), or units of packed cells (P = .4). Diuretic use in trauma patients with an OA after 2 laparotomies was not associated with successful PFC.
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Cavidade Abdominal , Traumatismos Abdominais , Técnicas de Fechamento de Ferimentos Abdominais , Tratamento de Ferimentos com Pressão Negativa , Abdome/cirurgia , Cavidade Abdominal/cirurgia , Traumatismos Abdominais/cirurgia , Diuréticos/uso terapêutico , Fasciotomia , Humanos , Laparotomia , Estudos RetrospectivosRESUMO
BACKGROUND: Obesity is a risk factor for tracheostomy-related complications. We aimed to investigate whether obesity was associated with a risk of unplanned tracheostomy dislodgement or decannulation (DD). METHODS: Retrospective review of patients undergoing tracheostomy at a single institution from 2013 to 2019 was performed. The primary outcome was unplanned DD within 42 days. Obesity was assessed by body mass index (BMI) and skin-to-trachea distance (STT) measured on computed tomographic images. RESULTS: 25 (12%) episodes of unplanned DD occurred in 213 patients within 42 days. BMI ≥35 kg/m2 was associated with STT ≥80 mm (p < 0.0001). On multivariate analysis, STT ≥80 mm but not BMI was an independent predictor of unplanned DD (hazard ratio = 8.34 [95% confidence interval 2.85-24.4]). CONCLUSIONS: STT ≥80 mm was a better predictor of unplanned DD than BMI. Assessment of STT in addition to BMI may be useful to identify patients that would benefit from extended length tracheostomy tubes.
Assuntos
Obesidade , Traqueostomia , Índice de Massa Corporal , Humanos , Obesidade/complicações , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
INTRODUCTION: Blunt traumatic injuries are a leading cause of morbidity and mortality in the pediatric population. Contrast-enhanced multidetector computed tomography is the best imaging tool for screening patients at risk of blunt abdominal injury. The Pediatric Emergency Care Applied Research Network (PECARN) abdominal rule was derived to identify patients at low risk for significant abdominal injury who do not require imaging. METHODS: We conducted a retrospective review of pediatric patients with blunt trauma to validate the PECARN rule in a non-pediatric specialized hospital from February 3, 2013, through December 31, 2019. We excluded those with penetrating or mild isolated head injury. The PECARN decision rule was retrospectively applied for the presence of a therapeutic intervention, defined as a laparotomy, angiographic embolization, blood transfusion, or administration of intravenous fluids for pancreatic or gastrointestinal injury. Sensitivity and specificity analysis were conducted along with the negative and positive predictive values. RESULTS: A total of 794 patients were included in the final analysis; 23 patients met the primary outcome for an acute intervention. The PECARN clinical decision rule (CDR) had a sensitivity of 91.3%, a negative predictive value of 99.5, and a negative likelihood ration of 0.16. CONCLUSION: In a non-pediatric specialty hospital, the PECARN blunt abdominal CDR performed with comparable sensitivity and negative predictive value to the derivation and external validation study performed at specialized children's hospitals.