Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 162
Filtrar
1.
BMC Geriatr ; 21(1): 646, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34784883

RESUMO

BACKGROUND: Among potentially modifiable risk factors for delirium, transfers between wards, hospitals and other facilities have been mentioned with low evidence. TRADE (TRAnsport and DElirium in older people) was set up to investigate i) the impact of transfer and/or discharge on the onset of delirium in older adults and ii) feasibility and acceptance of a developed complex intervention targeting caregiver's participation during and after hospital discharge or transfer on cognition and the onset of delirium in older adults. METHODS: The study is designed according to the guidelines of the UK Medical Research Council (MRC) for development and evaluation of complex interventions and comprises two steps: development and feasibility/piloting. The development phase includes i) a multicenter observational prospective cohort study to assess delirium incidence and cognitive decline associated with transfer and discharge, ii) a systematic review of the literature, iii) stakeholder focus group interviews and iv) an expert workshop followed by a Delphi survey. Based on this information, a complex intervention to better and systematically involve family caregivers in discharge and transport was developed. The intervention will be tested in a pilot study using a stepped wedge design with a detailed process and health economic evaluation. The study is conducted at four acute care hospitals in southwest Germany. Primary endpoints are the delirium incidence and cognitive function. Secondary endpoints include prevalence of caregiver companionship, functional decline, cost and cost effectiveness, quality of discharge management and quality of admission management in admitting hospitals or nursing homes. Data will be collected prior to discharge as well as after 3, 7 and 90 days. DISCUSSION: TRADE will help to evaluate transfer and discharge as a possible risk factor for delirium. In addition, TRADE evaluates the impact and modifiability of caregiver's participation during patient's transfer or discharge on delirium incidence and cognitive decline providing the foundation for a confirmatory implementation study. TRIAL REGISTRATION: DRKS (Deutsches Register für klinische Studien) DRKS00017828 . Registered on 17th September 2019. Retrospectively registered.


Assuntos
Delírio , Alta do Paciente , Idoso , Cuidadores , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/prevenção & controle , Hospitais , Humanos , Estudos Multicêntricos como Assunto , Projetos Piloto , Estudos Prospectivos , Revisões Sistemáticas como Assunto
2.
Geriatr Orthop Surg Rehabil ; 12: 21514593211050153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733579

RESUMO

Introduction: Femoral neck fractures in the elderly are a major event and are rising in incidence over the last decade. Advancing age and numerous comorbidities largely account for high mortality rate and require geriatric expertise. Treatment options are total hip arthroplasty (THA), hemiarthroplasty (HA) or osteosynthesis. Literature suggests THA or HA for better outcomes, although no clear guidelines exist. Material and methods: A retrospective chart review was performed of 63 patients (80 ± 11 years; 32 women, 31 men) with Garden one femoral neck fractures treated between June 2018 and June 2020 with either HA or internal fixation with the Femoral Neck System (FNS). Primary outcome measures were surgical and non-surgical complication rates and best achievable mobilization during the hospital stay. Results: Thirty four patients were treated with HA, and 29 with the FNS. Mobilization was measured using the Charité Mobility Index (CHARMI). No difference between age, ASA, CCI or preoperative CHARMI was found. The CHARMI was significantly lower in the HA group. No difference in surgical complications was found. The HA cohort showed more non-surgical complications, a longer ICU stay and more blood transfusions. Hospitalization was significant longer in the HA than the FNS cohort (15.1 ± 5.1 vs 9.8 ± 3.8 days). Radiographic controls were performed after 6 and 12 weeks. The FNS group showed a mean shortening of 3.3 mm. 4 of 21 patient had shortening >5 mm. 20 of 21 patients showed radiographic signs of bone healing after 3 months. Conclusion: Early results with the FNS show faster recovery than patient with hemiarthroplasty. Internal fixation with the FNS may be an option in non-displaced femoral neck fractures. Further studies should be performed to better evaluate the FNS compared to traditional internal fixation methods and arthroplasty.

3.
J Bone Miner Res ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633111

RESUMO

Mast cells are important tissue-resident sensor and effector immune cells but also play a major role in osteoporosis development. Mast cells are increased in numbers in the bone marrow of postmenopausal osteoporotic patients, and mast cell-deficient mice are protected from ovariectomy (OVX)-induced bone loss. In this study, we showed that mast cell-deficient Mcpt5-Cre R-DTA mice were protected from OVX-induced disturbed fracture healing, indicating a critical role for mast cells in the pathomechanisms of impaired bone repair under estrogen-deficient conditions. We revealed that mast cells trigger the fracture-induced inflammatory response by releasing inflammatory mediators, including interleukin-6, midkine (Mdk), and C-X-C motif chemokine ligand 10 (CXCL10), and promote neutrophil infiltration into the fracture site in OVX mice. Furthermore, mast cells were responsible for reduced osteoblast and increased osteoclast activities in OVX mice callus, as well as increased receptor activator of NF-κB ligand serum levels in OVX mice. Additional in vitro studies with human cells showed that mast cells stimulate osteoclastogenesis by releasing the osteoclastogenic mediators Mdk and CXCL10 in an estrogen-dependent manner, which was mediated via the estrogen receptor alpha on mast cells. In conclusion, mast cells negatively affect the healing of bone fractures under estrogen-deficient conditions. Hence, targeting mast cells might provide a therapeutic strategy to improve disturbed bone repair in postmenopausal osteoporosis. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

4.
Artigo em Inglês | MEDLINE | ID: mdl-34545420

RESUMO

BACKGROUND: The treatment of fragility fractures of the pelvis is rising challenge for orthopedic trauma surgeons. Operative treatment should allow immediate full weight bearing and early mobilisation but should also be as minimal invasive as possible. Sacroiliac (SI) or transsacral transiliac screws (TSTI) alone or depending on the fracture in combination with an external fixator meets both of these criteria. MATERIAL AND METHODS: The outcome of 121 operatively treated patients with fragility fractures of the pelvis were evaluated in this retrospective study. Depending on the type of fracture the patients were treated with navigated SI screw or TSTI screw alone or in combination with an external fixator. All patients were operated in supine position in a hybrid-OR, which consists of a fixed robotic 3D flatpanel detector (Artis zeego, Siemens Healthineers, Germany) and a navigation system (BrainLab Curve, BrainLab, Germany). RESULTS: 37 patients were treated with either one or two SI screws and 57 with one TSTI screw. An additional external fixator was combined with SI screws in 17 patients and with TSTI screws in 10 patients. The preoperative pain score was significantly higher compared to the postoperative score (5.1 ± 2.5 vs 2.2 ± 1.9, p < 0.05). Follow-up at 6 month was possible for 106 patients which showed screw loosening in 16.3% of the SI Screws (n = 49) compared to only 5.2% of TSTI screws (n = 57). No screw loosening was seen in the combination of TSTI-screw and external fixator (n = 10). There were two septic and three aseptic pin loosenings of the external fixator. Overall only one patient needed revision surgery due to screw loosening and local irritation. Overall 75.2% (n = 91) of the patients could be released in their home or in a rehabilitation unit and only 14% (n = 17) were released to a nursing home due to immobility despite the operation. Non-surgical complications rate was 21.5%. CONCLUSION: SI or TSTI screws with possible combination with an external fixator show early pain relief and allows most of the patients to keep their former level of independence. With an also low surgical complication rate, it proved to be a safe and reliable treatment for fragility fractures of the pelvis. Due the effective pain relief and the minimal invasive approach, early mobilisation is possible and might prevent typical non-surgical complications which are very common during conservative treatment.

5.
Unfallchirurg ; 2021 Sep 30.
Artigo em Alemão | MEDLINE | ID: mdl-34591137

RESUMO

BACKGROUND AND OBJECTIVE: The isolated proximal radius fracture in children is a quite rare injury. In difference to adults a conservative treatment is often possible. But in case of increasing dislocation the indication for surgery is given. Options for an operative treatment are "closed reduction", "percutaneous reduction", "intramedullary nailing", "open reduction" with and without fixation. Aim of this study is to compare these procedures with each other. STUDY DESIGN AND METHODS: This was a retrospective investigation and 82 patients who underwent surgery after an isolated proximal radius fracture were included. Fracture types were classified according to the AO (working group for osteosynthesis questions)/OTA (Orthopedic Trauma Association) classification. The preoperative and postoperative degrees of axis deviation were compared and were considered to be a measure of the quality of treatment. RESULTS: The lowest degree of axis deviation resulted by open reduction and implantation of K­wires (15,8°) and implantation of headless compression screws (HCS, 16°). Closed reduction without any fixation resulted in 19°, with implantation of an TEN (titan elastic nail) in 20° and the open reduction without any fixation resulted in 21° of axis deviation. No correlation was observed concerning the fracture type and the postoperative axis deviation. CONCLUSION: The study shows that the postoperative result does not depend on the fracture type (according to the AO/OTA classification) but on the surgical procedure. Despite the good radiological results in open reduction and internal fixation this procedure should be reserved for difficult situations in which less invasive surgical procedures fail, to avoid aseptic bone necrosis.

6.
J Clin Med ; 10(14)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34300323

RESUMO

Life-threatening polytrauma results in early activation of the complement and apoptotic system, as well as leukocytes, ultimately leading to the clearance of damaged cells. However, little is known about interactions between the complement and apoptotic systems in PMN (polymorphonuclear neutrophils) after multiple injuries. PMN from polytrauma patients and healthy volunteers were obtained and assessed for apoptotic events along the post-traumatic time course. In vitro studies simulated complement activation by the exposure of PMN to C3a or C5a and addressed both the intrinsic and extrinsic apoptotic pathway. Specific blockade of the C5a-receptor 1 (C5aR1) on PMN was evaluated for efficacy to reverse complement-driven alterations. PMN from polytrauma patients exhibited significantly reduced apoptotic rates up to 10 days post trauma compared to healthy controls. Polytrauma-induced resistance was associated with significantly reduced Fas-ligand (FasL) and Fas-receptor (FasR) on PMN and in contrast, significantly enhanced FasL and FasR in serum. Simulation of systemic complement activation revealed for C5a, but not for C3a, a dose-dependent abrogation of PMN apoptosis in both intrinsic and extrinsic pathways. Furthermore, specific blockade of the C5aR1 reversed C5a-induced PMN resistance to apoptosis. The data suggest an important regulatory and putative mechanistic and therapeutic role of the C5a/C5aR1 interaction on PMN apoptosis after polytrauma.

7.
Nat Commun ; 12(1): 2542, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953174

RESUMO

Lateral heterojunctions of atomically precise graphene nanoribbons (GNRs) hold promise for applications in nanotechnology, yet their charge transport and most of the spectroscopic properties have not been investigated. Here, we synthesize a monolayer of multiple aligned heterojunctions consisting of quasi-metallic and wide-bandgap GNRs, and report characterization by scanning tunneling microscopy, angle-resolved photoemission, Raman spectroscopy, and charge transport. Comprehensive transport measurements as a function of bias and gate voltages, channel length, and temperature reveal that charge transport is dictated by tunneling through the potential barriers formed by wide-bandgap GNR segments. The current-voltage characteristics are in agreement with calculations of tunneling conductance through asymmetric barriers. We fabricate a GNR heterojunctions based sensor and demonstrate greatly improved sensitivity to adsorbates compared to graphene based sensors. This is achieved via modulation of the GNR heterojunction tunneling barriers by adsorbates.

8.
Sci Rep ; 11(1): 8503, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33875675

RESUMO

Musculoskeletal injuries are the most common reason for surgery in severely injured patients. In addition to direct cardiac damage after physical trauma, there is rising evidence that trauma induces secondary cardiac structural and functional damage. Previous research associates hip fractures with the appearance of coronary heart disease: As 25% of elderly patients developed a major adverse cardiac event after hip fracture. 20 male pigs underwent femur fracture with operative stabilization via nailing (unreamed, reamed, RIA I and a new RIA II; each group n = 5). Blood samples were collected 6 h after trauma and the concentration of troponin I and heart-type fatty acid binding protein (HFABP) as biomarkers for EMD were measured. At baseline and 6 h after trauma, transesophageal ECHO (TOE) was performed; and invasive arterial and left ventricular blood pressure were measured to evaluate the cardiac function after femur fracture. A systemic elevation of troponin I and HFABP indicate an early myocardial damage after femur fracture in pigs. Furthermore, various changes in systolic (ejection fraction and cardiac output) and diastolic (left ventricular end-diastolic pressure, mitral valve deceleration time and E/A ratio) parameters illustrate the functional impairment of the heart. These findings were accompanied by the development of valvular dysfunction (pulmonary and tricuspid valve). To the best of our knowledge, we described for the first time the development of functional impairment of the heart in the context of EMD after long bone fracture in pigs. Next to troponin and HFABP elevation, alterations in the systolic and diastolic function occurred and were accompanied by pulmonary and tricuspid valvular insufficiency. Regarding EMD, none of the fracture stabilization techniques (unreamed nailing, reaming, RIA I and RIA II) was superior.


Assuntos
Cardiomiopatias/patologia , Fraturas do Fêmur/complicações , Fêmur/cirurgia , Fixação Intramedular de Fraturas/efeitos adversos , Doenças das Valvas Cardíacas/patologia , Animais , Cardiomiopatias/etiologia , Doenças das Valvas Cardíacas/etiologia , Masculino , Suínos
9.
Z Orthop Unfall ; 2021 Apr 19.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-33873225

RESUMO

BACKGROUND: Fractures of the proximal femur in the elderly population are rising. Teaching the appropriate surgical treatment of these fractures is of paramount importance. The aim of the study was to evaluate differences in outcome of surgical procedures between supervised trainees and senior surgeons. OBJECTIVE: Are there more surgical complications, poorer quality or an increased operating time if the procedure (in this case: fixation of proximal femur fractures) is performed by trainees under supervision in comparison to experienced surgeons. MATERIAL AND METHODS: All patients treated with the proximal femur nail antirotation (PFNA) between 2015 and 2016 at a level one trauma centre were included in this study. The retrospective review of the 299 patients compared supervised surgical trainees and senior surgeons. Parameters included operating time, tip apex distance, position of the blade, Hb-difference, transfusion rate, surgical complications as well as mortality, and were compared between the groups. RESULTS: 153 of 299 procedures were performed by supervised surgical trainees. In comparison to senior surgeons, there was no significant difference in operating time (WA 54.48 min; OA 60.47 min; p > 0,05), Hb-difference (WA 2.8 g/dl; OA 2.6 g/dl; p > 0.05), tip-apex distance (WA 21.2 mm; OA 20.5 mm, p = 0.37) or rate of surgical complications. There was no difference in the rate of optimal blade positions between the groups (WA 87.5%; OA 89.0%; p = 0.366). Furthermore, mortality showed no difference between the groups, but was greater in older patients or high ASA grade. CONCLUSION: Supervised surgical training during treatment of proximal femur fractures shows no increase in operating time, complications or mortality and no difference in quality. With the fast growth of the elderly population, surgical training of fragility fractures should receive more attention in the future.

10.
Int J Mol Sci ; 22(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803323

RESUMO

Periodontitis is the inflammatory destruction of the tooth-surrounding and -supporting tissue, resulting at worst in tooth loss. Another locally aggressive disease of the oral cavity is tooth resorption (TR). This is associated with the destruction of the dental mineralized tissue. However, the underlying pathomechanisms remain unknown. The complement system, as well as mast cells (MCs), are known to be involved in osteoclastogenesis and bone loss. The complement factors C3 and C5 were previously identified as key players in periodontal disease. Therefore, we hypothesize that complement factors and MCs might play a role in alveolar bone and tooth resorption. To investigate this, we used the cat as a model because of the naturally occurring high prevalence of both these disorders in this species. Teeth, gingiva samples and serum were collected from domestic cats, which had an appointment for dental treatment under anesthesia, as well as from healthy cats. Histological analyses, immunohistochemical staining and the CH-50 and AH-50 assays revealed increased numbers of osteoclasts and MCs, as well as complement activity in cats with TR. Calcifications score in the gingiva was highest in animals that suffer from TR. This indicates that MCs and the complement system are involved in the destruction of the mineralized tissue in this condition.


Assuntos
Perda do Osso Alveolar/metabolismo , Complemento C3/metabolismo , Complemento C5/metabolismo , Mastócitos/metabolismo , Periodontite/metabolismo , Reabsorção de Dente/metabolismo , Perda do Osso Alveolar/patologia , Animais , Gatos , Mastócitos/patologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Periodontite/patologia , Reabsorção de Dente/patologia
11.
Soft Matter ; 17(14): 3929-3936, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33720237

RESUMO

The electric-field driven transport of proteins across the liquid-liquid interface in an aqueous two-phase system (ATPS) is studied in a microfluidic device using fluorescence microscopy. An ATPS containing polyethylene glycol (PEG) and dextran is employed, and bovine serum albumin (BSA) and bovine γ-globulins (BγG) are considered as model proteins. It is shown that both proteins, initially in the dextran-rich phase, accumulate at the liquid-liquid interface, preferably close to the three-phase contact line between the two liquid phases and the microchannel wall. It is in these regions where the proteins penetrate into the PEG-rich phase. The transport resistance of the liquid-liquid interface is higher for BγG than for BSA, such that a much larger molar flux of BSA into the PEG phase is observed. This opens up the opportunity of separating different protein species by utilizing differences in the transport resistance at the interface. A mathematical model is developed, accounting for adsorption and desorption processes at the liquid-liquid interface. The underlying theoretical concept is that of an electrostatic potential minimum formed by superposing the applied electric field and the field due to the Donnan potential at the interface. A fit of the model parameters to the experimental data results in good agreement between theory and experiments, thereby corroborating the underlying picture.


Assuntos
Polietilenoglicóis , Água , Adsorção , Soroalbumina Bovina , Eletricidade Estática
12.
J Orthop Translat ; 28: 39-46, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33717980

RESUMO

Background: Trauma is the leading cause of death and disability worldwide, especially in the young population. Cardiac injuries are an independent predictor for a poor overall outcome after trauma. The aim of the present study was to analyze systemic inflammation as well as local cardiac inflammation after experimental limb-, neuro- and combined trauma in mice. Methods: Male C57BL/6 mice received either a closed tibia fracture (Fx), isolated traumatic brain injury (TBI) or a combination of both (Fx â€‹+ â€‹TBI). Control animals underwent sham procedure. After 6 and 24 â€‹h, systemic levels of inflammatory mediators were analyzed, respectively. Locally, cardiac inflammation and cardiac structural alterations were investigated in left ventricular tissue of mice 6 and 24 â€‹h after trauma. Results: Mice showed enhanced systemic inflammation after combined trauma, which was manifested by increased levels of KC, MCP-1 and G-CSF. Locally, mice exhibited increased expression of inflammatory cytokines (IL-1ß, TNF) in heart tissue, which was probably mediated via toll-like receptor (TLR) signaling. Furthermore, mice demonstrated a redistribution of connexin 43 in cardiac tissue, which appeared predominantly after combined trauma. Besides inflammation and structural cardiac alterations, expression of glucose transporter 4 (GLUT4) mRNA was increased in the heart early after TBI and after combination of TBI and limb fracture, indicating a modification of energy metabolism. Early after combination of TBI and tibia fracture, nitrosative stress was increased, manifested by elevation of nitrotyrosine in cardiac tissue. Finally, mice showed a trend of increased systemic levels of cardiac troponin I and heart-fatty acid binding protein (HFABP) after combined trauma, which was associated with a significant decrease of troponin I and HFABP mRNA expression in cardiac tissue after TBI and combination of TBI and limb fracture. Conclusion: Mice exhibited early cardiac alterations as well as alterations in cardiac glucose transporter expression, indicating a modification of energy metabolism, which might be linked to increased systemic- and local cardiac inflammation after limb-, neuro- and combined trauma. These cardiac alterations might predispose individuals for secondary cardiac damage after trauma that might compromise cardiac function after TBI and long bone fracture. Translational potential statement: Injuries to the head and extremities frequently occur after severe trauma. In our study, we analyzed the effects of closed tibia fracture, isolated TBI, and the combination of both injuries with regard to the development of post-traumatic secondary cardiac injuries.

13.
Sci Rep ; 11(1): 1151, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441945

RESUMO

One third of multiple trauma patients present abnormal echocardiographic (ECHO) findings. Therefore, ECHO diagnostic after trauma is indicated in case of hemodynamic instability, shock, after chest trauma and after cardiac arrest. 20 male pigs underwent multiple trauma. Blood samples were collected 4 and 6 h after trauma and concentrations of heart-type fatty acid binding protein (HFABP) as a biomarker for EMD were measured. Myocardial damage was evaluated by scoring Hematoxylin-Eosin stained sections. At baseline, 3 and 6 h after trauma, transesophageal ECHO (TOE) was performed, invasive arterial and left ventricular blood pressure were measured to evaluate the cardiac function after multiple trauma. Systemic HFABP concentrations were elevated, furthermore heart injury score in multiple trauma animals was increased determining EMD. A significant decrease of blood pressure in combination with a consecutive rise of heart frequency was observed. Ongoing depression of mean arterial pressure and diastolic blood pressure were accompanied by changes in ECHO-parameters indicating diastolic and systolic dysfunction. Furthermore, a valvular dysfunction was detected. In this study complex myocardial and valvular impairment after multiple trauma in pigs has been observed. Therefore, detection of EMD and progressive valvular dysfunction might be crucial and therapeutically relevant.


Assuntos
Cardiopatias/etiologia , Traumatismo Múltiplo/complicações , Miocárdio/patologia , Animais , Pressão Sanguínea , Coração/fisiopatologia , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/fisiopatologia , Masculino , Traumatismo Múltiplo/patologia , Traumatismo Múltiplo/fisiopatologia , Suínos
14.
Int J Mol Sci ; 22(2)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450984

RESUMO

Trauma remains a leading global cause of mortality, particularly in the young population. In the United States, approximately 30,000 patients with blunt cardiac trauma were recorded annually. Cardiac damage is a predictor for poor outcome after multiple trauma, with a poor prognosis and prolonged in-hospitalization. Systemic elevation of cardiac troponins was correlated with survival, injury severity score, and catecholamine consumption of patients after multiple trauma. The clinical features of the so-called "commotio cordis" are dysrhythmias, including ventricular fibrillation and sudden cardiac arrest as well as wall motion disorders. In trauma patients with inappropriate hypotension and inadequate response to fluid resuscitation, cardiac injury should be considered. Therefore, a combination of echocardiography (ECG) measurements, echocardiography, and systemic appearance of cardiomyocyte damage markers such as troponin appears to be an appropriate diagnostic approach to detect cardiac dysfunction after trauma. However, the mechanisms of post-traumatic cardiac dysfunction are still actively being investigated. This review aims to discuss cardiac damage following trauma, focusing on mechanisms of post-traumatic cardiac dysfunction associated with inflammation and complement activation. Herein, a causal relationship of cardiac dysfunction to traumatic brain injury, blunt chest trauma, multiple trauma, burn injury, psychosocial stress, fracture, and hemorrhagic shock are illustrated and therapeutic options are discussed.


Assuntos
Suscetibilidade a Doenças , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Disfunção Ventricular/etiologia , Disfunção Ventricular/fisiopatologia , Ferimentos e Lesões/complicações , Animais , Biomarcadores , Ativação do Complemento , Gerenciamento Clínico , Metabolismo Energético , Cardiopatias/diagnóstico , Cardiopatias/metabolismo , Testes de Função Cardíaca , Humanos , Índice de Gravidade de Doença , Disfunção Ventricular/diagnóstico , Disfunção Ventricular/metabolismo
15.
Front Immunol ; 11: 1789, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983087

RESUMO

Initially underestimated as platelet dust, extracellular vesicles are continuously gaining interest in the field of inflammation. Various studies addressing inflammatory diseases have shown that microvesicles (MVs) originating from different cell types are systemic transport vehicles carrying distinct cargoes to modulate immune responses. In this study, we focused on the clinical setting of multiple trauma, which is characterized by activation and dysfunction of both, the fluid-phase and the cellular component of innate immunity. Given the sensitivity of neutrophils for the complement anaphylatoxin C5a, we hypothesized that increased C5a production induces alterations in MV shedding of neutrophils resulting in neutrophil dysfunction that fuels posttraumatic inflammation. In a mono-centered prospective clinical study with polytraumatized patients, we found significantly increased granulocyte-derived MVs containing the C5a receptor (C5aR1, CD88) on their surface. This finding was accompanied by a concomitant loss of C5aR1 on granulocytes indicative of an impaired cellular chemotactic and pro-inflammatory neutrophil functions. Furthermore, in vitro exposure of human neutrophils (from healthy volunteers) to C5a significantly increased MV shedding and C5aR1 loss on neutrophils, which could be blocked using the C5aR1 antagonist PMX53. Mechanistic analyses revealed that the interaction between C5aR1 signaling and the small GTPase Arf6 acts as a molecular switch for MV shedding. When neutrophil derived, C5a-induced MV were exposed to a complex ex vivo whole blood model significant pro-inflammatory properties (NADPH activity, ROS and MPO generation) of the MVs became evident. C5a-induced MVs activated resting neutrophils and significantly induced IL-6 secretion. These data suggest a novel role of the C5a-C5aR1 axis: C5a-induced MV shedding from neutrophils results in decreased C5aR1 surface expression on the one hand, on the other hand it leads to profound inflammatory signals which likely are both key drivers of the neutrophil dysfunction which is regularly observed in patients suffering from multiple traumatic injuries.


Assuntos
Micropartículas Derivadas de Células/imunologia , Complemento C5a/metabolismo , Imunidade Inata , Mediadores da Inflamação/metabolismo , Traumatismo Múltiplo/imunologia , Neutrófilos/imunologia , Fatores de Ribosilação do ADP/metabolismo , Adulto , Estudos de Casos e Controles , Micropartículas Derivadas de Células/metabolismo , Feminino , Humanos , Escala de Gravidade do Ferimento , Interleucina-6/metabolismo , Cinética , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/sangue , Traumatismo Múltiplo/diagnóstico , NADP/metabolismo , Neutrófilos/metabolismo , Peroxidase/metabolismo , Estudos Prospectivos , Espécies Reativas de Oxigênio/metabolismo , Receptor da Anafilatoxina C5a/metabolismo , Transdução de Sinais , Adulto Jovem
16.
Front Immunol ; 11: 2081, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983160

RESUMO

Trauma represents a major socioeconomic burden worldwide. After a severe injury, hemorrhagic shock (HS) as a frequent concomitant aspect is a central driver of systemic inflammation and organ damage. The kidney is often strongly affected by traumatic-HS, and acute kidney injury (AKI) poses the patient at great risk for adverse outcome. Recently, thirty-eight-negative kinase 1 (TNK1) was proposed to play a detrimental role in organ damage after trauma/HS. Therefore, we aimed to assess the role of TNK1 in HS-induced kidney injury in a murine and a post hoc analysis of a non-human primate model of HS comparable to the clinical situation. Mice and non-human primates underwent resuscitated HS at 30 mmHg for 60 min. 5 h after the induction of shock, animals were assessed for systemic inflammation and TNK1 expression in the kidney. In vitro, murine distal convoluted tubule cells were stimulated with inflammatory mediators to gain mechanistic insights into the role of TNK1 in kidney dysfunction. In a translational approach, we investigated blood drawn from either healthy volunteers or severely injured patients at different time points after trauma (from arrival at the emergency room and at fixed time intervals until 10 days post injury; identifier: NCT02682550, https://clinicaltrials.gov/ct2/show/NCT02682550). A pronounced inflammatory response, as seen by increased IL-6 plasma levels as well as early signs of AKI, were observed in mice, non-human primates, and humans after trauma/HS. TNK1 was found in the plasma early after trauma-HS in trauma patients. Renal TNK1 expression was significantly increased in mice and non-human primates after HS, and these effects with concomitant induction of apoptosis were blocked by therapeutic inhibition of complement C3 activation in non-human primates. Mechanistically, in vitro data suggested that IL-6 rather than C3 cleavage products induced upregulation of TNK1 and impaired barrier function in renal epithelial cells. In conclusion, these data indicate that C3 inhibition in vivo may inhibit an excessive inflammatory response and mediator release, thereby indirectly neutralizing TNK1 as a potent driver of organ damage. In future studies, we will address the therapeutic potential of direct TNK1 inhibition in the context of severe tissue trauma with different degrees of additional HS.


Assuntos
Proteínas Fetais/metabolismo , Proteínas Tirosina Quinases/metabolismo , Choque Hemorrágico/metabolismo , Ferimentos e Lesões/metabolismo , Injúria Renal Aguda , Animais , Células Cultivadas , Complemento C3/metabolismo , Proteínas Fetais/genética , Voluntários Saudáveis , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Rim , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Primatas , Proteínas Tirosina Quinases/genética
17.
Artigo em Inglês | MEDLINE | ID: mdl-32880704

RESUMO

INTRODUCTION: After surgical treatment of injuries of the lower extremity, partial weight bearing is often suggested until soft tissue consolidation. It is doubtful, if this recommendation can be implemented, even in the case that a patient is performing partial weight bearing with a physical therapist. Consequently the question remains, if patients are able to implement partial weight bearing after surgery and which factors favor incompliance. MATERIALS AND METHODS: 49 patients, who underwent surgical treatment after injuries of the lower extremity, were equipped with electronic shoe insoles on both sides. Different weight bearing instructions were given depending on the type of injury and surgery (full weight bearing vs. 20 kg weight bearing vs. non-weight bearing). Besides loading, other factors like age, gender, weight and physical activity were evaluated. Statistical analysis was performed using Chi-square and Fisher's exact test with significance set at a p value < 0.05. RESULTS: 25 of the 40 patients, who had to perform non- or partial weight bearing, were not able to follow postoperative instructions (compliance rate 37.5%). The average loading of the whole collective was 32.6 kg (4.8-109.2 kg). The specification of loading had no statistically significant influence on real loading (p-value 0.39). Elderly patients were less able to follow instructions than younger patients (36 vs 30.2 kg). Physically active compared to non-active patients overloaded their injured extremity (37.8 vs 28.7 kg). Patients with a high body mass index (BMI) encountered more difficulties to perform partial weight bearing than lightweight patients (36.9 vs 25.1 kg). CONCLUSIONS: Most patients were not able to follow loading limitation, even a few days after surgery and even if the patients were trained by a physiotherapist. Excessive weight bearing-related complications should be evaluated.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32865595

RESUMO

PURPOSE: Operative timing, perioperative management and postoperative rehabilitation are rising challenges in orthopedic geriatric trauma. The aim of this study was to determine the outcome of patients with dementia or with a high number of comorbidities treated with hemiprosthesis after hip fracture. Literature regarding patients with high comorbidities is scarce, leaving nothing but endoprosthetic treatment for even the sickest, immobile patients. METHODS: A retrospective chart review of 326 patients (mean age 81 ± 9 years; 230 women and 96 men) with hip fractures treated between 2012 and 2017 with a hemiprosthesis was performed. Primary outcome measures were surgical and nonsurgical complication rates, best achievable mobilisation during the hospital stay and mortality. RESULTS: Patients with dementia had 20-fold increased risk to be bedridden after surgery and ninefold increased risk of dying (p < 0.005). Furthermore, they needed significantly more revision surgeries because of surgical complications. Patients classified ASA IV and V had significantly lower postoperative mobilization levels with only 10% able to walk with crutches and 53% bedridden. They also had significantly more non-surgical complications while dementia had no effect on non-surgical complication rate. CONCLUSION: Patients classified ASA IV and V or suffering dementia show poor outcome after hip fracture treated with hemiprosthesis. Multidisciplinary approaches including surgeons, geriatricians, physiotherapists and psychiatrists are needed to improve the outcome of these patients. Especially in a subgroup of patients, where no mobilization is expected, alternative treatment options may be considered.

19.
J Orthop Res ; 38(12): 2608-2618, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32827323

RESUMO

Cardiac injuries are recorded after multiple trauma and are associated with a poor patient outcome. Reaming prior to locked intramedullary nailing is a frequently used technique to stabilize femoral diaphysis fractures. However, in polytraumatized patients, complications such as fat emboli and acute respiratory distress syndrome have been associated with reaming. The reaming irrigator aspirator (RIA) system provides concomitant irrigation and suction of the intramedullary contents, and should, therefore, reduce reaming-associated complications. The aim of the study was to investigate cardiac function after multiple trauma with regard to two different RIA devices (RIAI vs RIAII). 15 male pigs were included in the study. Pigs received either sham treatment or multiple trauma (chest trauma, femur fracture, liver laceration, and hemorrhagic shock), followed by intramedullary nailing after reaming with either the RIAI or RIAII system (RIAII: reduced diameter of the reamer, improved control of irrigation and suction). Cardiac function was assessed by transesophageal echocardiography and systemic inflammation as well as local cardiac damage examined. Pigs of both treatment groups showed impaired cardiac function, valvular insufficiency, and cardiac damage. Systemic inflammation and local cardiac alterations were observed which might contribute to early myocardial damage in vivo. Multiple trauma including long-bone fracture and subsequent intramedullary reaming induces cardiac dysfunction and valvular insufficiency, which might be linked to both mechanical cardiac injury and increased systemic inflammation. 6 hours after trauma there are less differences between RIAI and RIAII treatment with regard to post-traumatic cardiac consequences in multiple injured pigs, indicating no beneficial effect of RIAII over RIAI.


Assuntos
Fixação Intramedular de Fraturas/efeitos adversos , Coração/fisiopatologia , Traumatismo Múltiplo/fisiopatologia , Alarminas/sangue , Animais , Biomarcadores/sangue , Ativação do Complemento , Proteína 3 Ligante de Ácido Graxo/sangue , Fixação Intramedular de Fraturas/instrumentação , Fixação Intramedular de Fraturas/métodos , Masculino , Camundongos , Traumatismo Múltiplo/sangue , Suínos , Irrigação Terapêutica/efeitos adversos , Irrigação Terapêutica/instrumentação , Irrigação Terapêutica/métodos , Troponina I/sangue
20.
PLoS One ; 15(6): e0235220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584885

RESUMO

BACKGROUND: Approximately 30,000 patients with blunt cardiac trauma are recorded each year in the United States. Blunt cardiac injuries after trauma are associated with a longer hospital stay and a poor overall outcome. Organ damage after trauma is linked to increased systemic release of pro-inflammatory cytokines and damage-associated molecular patterns. However, the interplay between polytrauma and local cardiac injury is unclear. Additionally, the impact of surgical intervention on this process is currently unknown. This study aimed to determine local cardiac immunological and structural alterations after multiple trauma. Furthermore, the impact of the chosen fracture stabilization strategy (reamed versus non-reamed femoral nailing) on cardiac alterations was studied. EXPERIMENTAL APPROACH: 15 male pigs were either exposed to multiple trauma (blunt chest trauma, laparotomy, liver laceration, femur fracture and haemorrhagic shock) or sham conditions. Blood samples as well as cardiac tissue were analysed 4 h and 6 h after trauma. Additionally, murine HL-1 cells were exposed to a defined polytrauma-cocktail, mimicking the pro-inflammatory conditions after multiple trauma in vitro. RESULTS: After multiple trauma, cardiac structural changes were observed in the left ventricle. More specifically, alterations in the alpha-actinin and desmin protein expression were found. Cardiac structural alterations were accompanied by enhanced local nitrosative stress, increased local inflammation and elevated systemic levels of the high-mobility group box 1 protein. Furthermore, cardiac alterations were observed predominantly in pigs that were treated by non-reamed intramedullary reaming. The polytrauma-cocktail impaired the viability of HL-1 cells in vitro, which was accompanied by a release of troponin I and HFABP. DISCUSSION: Multiple trauma induced cardiac structural alterations in vivo, which might contribute to the development of early myocardial damage (EMD). This study also revealed that reamed femoral nailing (reamed) is associated with more prominent immunological cardiac alterations compared to nailing without reaming (non-reamed). This suggests that the choice of the initial fracture treatment strategy might be crucial for the overall outcome as well as for any post-traumatic cardiac consequences.


Assuntos
Pinos Ortopédicos/efeitos adversos , Fraturas do Fêmur/cirurgia , Traumatismo Múltiplo/patologia , Miocárdio/patologia , Actinina/metabolismo , Animais , Cálcio/metabolismo , Linhagem Celular , Sobrevivência Celular , Conexina 43/metabolismo , Citocinas/análise , Citocinas/metabolismo , Desmina/metabolismo , Fraturas do Fêmur/patologia , Proteína HMGB1/análise , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Inflamação , Masculino , Camundongos , Traumatismo Múltiplo/metabolismo , Traumatismo Múltiplo/veterinária , Miocárdio/metabolismo , Estresse Nitrosativo , Suínos , Troponina I/análise
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...