RESUMO
OBJECTIVE: ApoC-III (apolipoprotein C-III) glycosylation can predict cardiovascular disease risk. Higher abundance of disialylated (apoC-III2) over monosialylated (apoC-III1) glycoforms is associated with lower plasma triglyceride levels. Yet, it remains unclear whether apoC-III glycosylation impacts TRL (triglyceride-rich lipoprotein) clearance and whether apoC-III antisense therapy (volanesorsen) affects distribution of apoC-III glycoforms. Approach and Results: To measure the abundance of human apoC-III glycoforms in plasma over time, human TRLs were injected into wild-type mice and mice lacking hepatic TRL clearance receptors, namely HSPGs (heparan sulfate proteoglycans) or both LDLR (low-density lipoprotein receptor) and LRP1 (LDLR-related protein 1). ApoC-III was more rapidly cleared in the absence of HSPG (t1/2=25.4 minutes) than in wild-type animals (t1/2=55.1 minutes). In contrast, deficiency of LDLR and LRP1 (t1/2=56.1 minutes) did not affect clearance of apoC-III. After injection, a significant increase in the relative abundance of apoC-III2 was observed in HSPG-deficient mice, whereas the opposite was observed in mice lacking LDLR and LRP1. In patients, abundance of plasma apoC-III glycoforms was assessed after placebo or volanesorsen administration. Volanesorsen treatment correlated with a statistically significant 1.4-fold increase in the relative abundance of apoC-III2 and a 15% decrease in that of apoC-III1. The decrease in relative apoC-III1 abundance was strongly correlated with decreased plasma triglyceride levels in patients. CONCLUSIONS: Our results indicate that HSPGs preferentially clear apoC-III2. In contrast, apoC-III1 is more effectively cleared by LDLR/LRP1. Clinically, the increase in the apoC-III2/apoC-III1 ratio on antisense lowering of apoC-III might reflect faster clearance of apoC-III1 because this metabolic shift associates with improved triglyceride levels.
Assuntos
Apolipoproteína C-III/sangue , Hipertrigliceridemia/tratamento farmacológico , Lipoproteínas HDL3/metabolismo , Oligonucleotídeos/administração & dosagem , Receptores de LDL/metabolismo , Animais , Apolipoproteína C-III/efeitos dos fármacos , Modelos Animais de Doenças , Glicosilação/efeitos dos fármacos , Humanos , Hipertrigliceridemia/sangue , Masculino , Camundongos , Terapia de Alvo Molecular/métodos , Receptores de LDL/efeitos dos fármacos , Valores de ReferênciaRESUMO
BACKGROUND: The purpose of this paper was to survey members of the American Shoulder and Elbow Surgeons (ASES) to assess their opinion on management options, help highlight important clinical factors, and elucidate surgical preferences for the treatment of a symptomatic meso-os. METHODS: An online questionnaire was distributed to the active members of the ASES. The survey queried surgeon demographics and perioperative management preferences, and presented multiple clinical case scenarios of patients with a presumed symptomatic, unstable os acromiale. RESULTS: There were 116 ASES members who responded to the survey, and 26% (n = 30) who stated they do not operatively manage a symptomatic os. We identified two main clusters of respondents. Cluster 1 (n = 67) (as compared to cluster 2, n = 19) was comprised of surgeons with significantly more experience treating a symptomatic os acromiale (p < 0.05). These surgeons regarded gender, age, BMI, and hand dominance as important clinical factors when deciding when to proceed to surgery. Overall, arthroscopic management of the os was preferred, but those surgeons more experienced in treating os acromiale preferred open reduction and internal fixation (ORIF) in specific clinical cases. CONCLUSION: The survey findings reflect the current lack of consensus in the treatment of a unstable, symptomatic os acromiale. Overall, arthroscopic management was preferred by most surgeons, though ORIF was preferred in certain clinical scenarios by those more experienced with os acromiale. The overall preference for arthroscopy suggests a possible shift in the treatment paradigm for patients with symptomatic meso-acromions, but higher level studies are needed to substantiate these findings.
Assuntos
Acrômio/cirurgia , Doenças do Desenvolvimento Ósseo/cirurgia , Acrômio/anormalidades , Acrômio/diagnóstico por imagem , Artroscopia , Doenças do Desenvolvimento Ósseo/terapia , Fixação Interna de Fraturas , Pesquisas sobre Atenção à Saúde , Humanos , Internet , Redução Aberta , Ortopedia/normas , Ortopedia/estatística & dados numéricosRESUMO
BACKGROUND: The effects of levosimendan (Levo) on injury patterns in the immature brain following cardiopulmonary bypass (CPB) are unknown. METHODS: Eighteen 3- to 4-wk-old anesthetized lambs, instrumented with vascular catheters and aortic and right carotid artery flow probes, were allocated to non-CPB, CPB, or CPB+Levo groups (each n = 6). After 120 min CPB with 90 min aortic cross-clamp, CPB animals received dopamine, and CPB+Levo animals both dopamine and Levo, for 4 h. All lambs then underwent brain magnetic resonance imaging, followed by postmortem brain perfusion fixation for immunohistochemical studies. RESULTS: In CPB lambs, aortic (P < 0.05) and carotid artery (P < 0.01) blood flows fell by 29 and 30%, respectively, between 2 and 4 h after cross-clamp removal but were unchanged in the CPB+Levo group. No brain injury was detectable with magnetic resonance imaging in either CPB or CPB+Levo lambs. However, on immunohistochemical analysis, white matter astrocyte density of both groups was higher than in non-CPB lambs (P < 0.05), while white matter microglial density was higher (P < 0.05), but markers of cortical oxidative stress were less prevalent in CPB+Levo than CPB lambs. CONCLUSION: While Levo prevented early postoperative falls in cardiac output and carotid artery blood flow in a lamb model of infant CPB, this was associated with heterogeneous neuroglial activation and manifestation of markers of oxidative stress.
Assuntos
Lesões Encefálicas/tratamento farmacológico , Ponte Cardiopulmonar/efeitos adversos , Hidrazonas/uso terapêutico , Piridazinas/uso terapêutico , Animais , Antiarrítmicos/uso terapêutico , Gasometria , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Débito Cardíaco/efeitos dos fármacos , Ponte Cardiopulmonar/métodos , Artérias Carótidas/efeitos dos fármacos , Modelos Animais de Doenças , Dopamina/química , Hemodinâmica/efeitos dos fármacos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Neuroglia/efeitos dos fármacos , Estresse Oxidativo , Ovinos , SimendanaRESUMO
Objective.Spatially fractionated radiotherapy is showing promise as a treatment modality. Initial focus was on beams of photons at low energy produced from a synchrotron but more recently research has expanded to include applications in proton therapy. Interest in photon beams remains and this is the focus of this paperApproach.This study presents a 3D printed tungsten minibeam collimator intended to produce peak-to-valley dose ratios (PVDR) of between seven and ten with a 1 MV, bremsstrahlung generated, photon beam. The design of the collimator is motivated by a Monte Carlo study estimating the PVDR for different collimator designs at different energies. This collimator was characterised on a clinical linear accelerator (Elekta VersaHD) as well as an orthovoltage unit.Main results.The performance of the fabricated collimator was measured on Elekta VersaHD running in unflattened mode with a 6 MV beam. On the Elekta VersaHD units the PVDR was measured to be between approximately 1.5 and 2.0 at 3 cm deep. For measurements with the orthovoltage unit PVDRs of greater than 10 were observed at a depth of 4 cm.Significance.The results confirmed that the predictions from simulation could be reproduced on linear accelerators currently in clinical usage, producing PVDRs between 2-2.5. Using the model to predict PVDRs using 1 MV photon beams, the threshold considered to produce enhanced normal tissue dose tolerance (>7) was surpassed. This suggests the possibility of using such techniques with versions of existing Linac technology which have been modified to operate at low energy and high beam currents.
Assuntos
Desenho de Equipamento , Método de Monte Carlo , Aceleradores de Partículas , Dosagem Radioterapêutica , Humanos , FótonsRESUMO
Glypican-3 (GPC3) is a membrane-associated glycoprotein that is significantly upregulated in hepatocellular carcinomas (HCC) with minimal to no expression in normal tissues. The differential expression of GPC3 between tumor and normal tissues provides an opportunity for targeted radiopharmaceutical therapy to treat HCC, a leading cause of cancer-related deaths worldwide. Methods: DOTA-RYZ-GPC3 (RAYZ-8009) comprises a novel macrocyclic peptide binder to GPC3, a linker, and a chelator that can be complexed with different radioisotopes. The binding affinity was determined by surface plasma resonance and radioligand binding assays. Target-mediated cellular internalization was radiometrically measured at multiple time points. In vivo biodistribution, monotherapy, and combination treatments with 177Lu or 225Ac were performed on HCC xenografts. Results: RAYZ-8009 showed high binding affinity to GPC3 protein of human, mouse, canine, and cynomolgus monkey origins and no binding to other glypican family members. Potent cellular binding was confirmed in GPC3-positive HepG2 cells and was not affected by isotope switching. RAYZ-8009 achieved efficient internalization on binding to HepG2 cells. Biodistribution study of 177Lu-RAYZ-8009 showed sustained tumor uptake and fast renal clearance, with minimal or no uptake in other normal tissues. Tumor-specific uptake was also demonstrated in orthotopic HCC tumors, with no uptake in surrounding liver tissue. Therapeutically, significant and durable tumor regression and survival benefit were achieved with 177Lu- and 225Ac-labeled RAYZ-8009, as single agents and in combination with lenvatinib, in GPC3-positive HCC xenografts. Conclusion: Preclinical in vitro and in vivo data demonstrate the potential of RAYZ-8009 as a theranostic agent for the treatment of patients with GPC3-positive HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Cães , Camundongos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/metabolismo , Glipicanas/metabolismo , Medicina de Precisão , Distribuição Tecidual , Macaca fascicularis/metabolismo , Peptídeos/metabolismoRESUMO
OBJECTIVES: Describe co-occurrence or clustering of microbial taxa in fracture-related infections to inform further exploration of infection-related interactions among them. DESIGN: Retrospective review. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Four hundred twenty-three patients requiring surgical intervention for deep surgical site infection between January 2006 and December 2015. INTERVENTION: None. MAIN OUTCOME MEASUREMENT: Connection between microbial taxa. RESULTS: Methicillin-resistant Staphylococcus aureus, methicillin-sensitive Staphylococcus aureus, and coagulase-negative Staphylococcus represented the majority of monomicrobial observations (71%). Gram-negative rods, gram-positive rods, and anaerobes presented more frequently in polymicrobial infections. Enterobacter, vancomycin-sensitive Enterococcus, and Pseudomonas are present in polymicrobial infections with the highest frequencies and represent the top 3 most important nodes within the microorganism framework, with the highest network centrality scores. CONCLUSIONS: The present study indicates that there are common microbial taxa (Enterobacter, Enterococcus, and Pseudomonas) that tend to co-occur with other microbes greater than 75% of the time. These commonly co-occurring microbes have demonstrated interactive relationships in other disease pathologies, suggesting that there may be similar important interactions in fracture-related infections. It is possible that these microbial communities play a role in the persistently high failure rate associated with management of infection after trauma. Future studies are needed to study the intermicrobial interactions that explain the frequency at which taxa co-occur. Understanding and potentially disrupting these intermicrobial relationships could inform improvements in the treatment of established infections and in the prevention of infection in high-risk patients. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Assuntos
Coinfecção , Fraturas Ósseas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/uso terapêutico , Coinfecção/tratamento farmacológico , Fraturas Ósseas/cirurgia , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecção da Ferida Cirúrgica/tratamento farmacológicoRESUMO
Purpose: Empiric antibiotic therapy for hand and upper-extremity infections aims to cover the most common causative organisms, which may change over time. The purpose of this study was to investigate the changes in the bacterial profile of upper-extremity infections over 2 decades at our institution. Methods: We performed a retrospective chart review of patients with upper-extremity infections treated at a single level 1 trauma center between 2001 and 2019. Patients older than 18 years who underwent surgical treatment for infection with operative cultures available were included. Patient demographics, comorbidities, and culture results were reviewed. Then, the distribution of organisms was analyzed for overall prevalence, and the profile of 2001-2010 was compared with that of 2010-2019 using a chi-square test. Results: A total of 237 patients (mean age, 43 years) met the criteria and were included in the study. Over the entire study period, the most isolated organism was Staphylococcus aureus, specifically the methicillin-resistant species. Methicillin-resistant S aureus remained the most common organism in both decades but declined over time from 47% in 2001-2010 to 27% in 2010-2019 (P < .05). There was a significant increase in the proportion of Streptococcus infections (from 6% to 17%; P < .05) and in polymicrobial infections (aerobic 8% to 28%, anaerobic 0% to 14%; P < .05). Enterobacter species were not isolated in 2001-2010 but comprised 13% of infections in the second decade (P < .05). Conclusions: Methicillin-resistant S aureus remains the most common organism isolated from upper-extremity infections, though there has been a decline over the last 20 years. Conversely, Streptococcal spp., Enterobacter spp. and polymicrobial infections have increased. This study demonstrates longitudinal shifts in the distribution of bacteria responsible for upper-extremity infections at our institution, and these trends can be considered when choosing future empiric therapy. Type of study/level of evidence: Prognostic IV.
RESUMO
INTRODUCTION: Rehabilitation of trauma patients is facilitated by surgical stabilization permitting weight bearing (WB) of the fractured extremity. Both-bone forearm fracture (BBFx) plate osteosynthesis is an accepted technique with high union and low complication rates; yet, postoperative WB protocols have not been adequately investigated. There exists concern for increased complications in plated BBFx fractures for patients prescribed immediate WB. We hypothesized that immediate WB of surgically treated BBFxs results in acceptable rates of complications. METHODS: Patients presenting to a Level-1 trauma center from 2007 to 2016 with a BBFx were identified retrospectively. Patients were skeletally mature, surgically treated with prescribed immediate WB protocol, and followed for 6 months or to fracture union. Collected data included demographics, fracture characteristics, associated injuries, and WB protocols for all extremities. Complications recorded included nonunion, hardware failure, and infection. Standard statistical comparisons were used to evaluate the risk of complication in polytrauma patients with modified lower extremity WB protocols (polytrauma group) and patients with no lower extremity WB restrictions (isolated group). RESULTS: Two hundred thirteen patients were included with 75 (35%) females and 138 (65%) males. Mean age was 40 years and mean follow-up was 46 weeks. There were 142 (67%) patients in the poly-trauma and 71 (33%) patients in the isolated groups. In the poly-trauma group 21 (10%) patients had bilateral lower extremity WB restrictions. There were 11 (6%) complications noted: 2 non-unions, 4 hardware failures, and 5 infections. Demographics did not vary between the two groups. There was no difference in complications in the isolated (5.7%) versus poly-trauma groups (5.0%) (P = 0.75). CONCLUSION: Immediate WB rehabilitation after BBFx plate osteosynthesis seems to be safe and associated with low nonunion and complication rates. Our results demonstrate that polytrauma patients using ambulatory aids for lower extremity injuries can immediately WB without increased risk compared with isolated BBFx patients.
Assuntos
Antebraço , Traumatismo Múltiplo , Adulto , Placas Ósseas , Feminino , Fixação Interna de Fraturas/efeitos adversos , Consolidação da Fratura , Humanos , Masculino , Traumatismo Múltiplo/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Suporte de CargaRESUMO
OBJECTIVE: Infection after fracture fixation is a potentially devastating outcome, and surgical management is frequently unsuccessful at clearing these infections. The purpose of this study is to determine if factors can be identified that are associated with treatment failure after operative management of a deep surgical site infection. METHODS: We retrospectively reviewed the billing system at a Level I trauma center between March 2006 and December 2015. We identified 451 patients treated for deep surgical site infection after fracture fixation at our center. A multivariate regression analysis was then performed to evaluate for factors associated with treatment failure. RESULTS: Mean follow-up was 2.3 years. One hundred fifty-six patients (35%) failed initial surgical management. Risk factors associated with treatment failure included initial culture results positive for polymicrobial organisms (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.4), removal of implants (OR, 1.9; 95% CI, 1.2-2.9), or Gustilo-Anderson IIIB/IIIC injury (OR, 2.0; 95% CI, 1.1-3.7). Increased body mass index and fulfilling the criteria to have a methicillin-resistant Staphylococcus aureus (MRSA) nasal swab screening showed a trend toward increased risk of failure. CONCLUSION: Treatment failure after deep surgical site infection was relatively common. Three distinct factors (polymicrobial infection, removal of implants, and IIIB/C fracture) were associated with failure to eradicate the infection in the first series of surgeries and antibiotics. These data might help guide clinicians as they counsel patients on the risk of treatment failure and might focus efforts to improve treatment toward patients at higher risk of treatment failure.
Assuntos
Fraturas Expostas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Fixação Interna de Fraturas , Fraturas Expostas/cirurgia , Humanos , Estudos Retrospectivos , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Infecção da Ferida Cirúrgica/epidemiologia , Falha de Tratamento , Resultado do TratamentoRESUMO
The authors assessed the effects of forearm rotation on the proximity of the radial nerve and medial collateral ligament (MCL) to a proximal and a more distal arthroscopic anterior elbow capsulectomy. Arthroscopy was performed on 10 cadaveric specimens. Sutures were passed lateral to medial at the level of the radiocapitellar joint and at the proximal edge of the annular ligament. Dissection measured the distance to the radial nerve from the lateral starting point and to the MCL from the medial exit point in varying degrees of forearm rotation. The extent of brachialis muscle coverage of the radial nerve was documented. The distance from the starting point to the radial nerve increased in pronation at both levels. The medial extent of the capsulectomy remained a safe distance from the MCL. Brachialis muscle covered the radial nerve at both levels. Pronation increases the capsulectomy safe zone, including more distally, before encountering the radial nerve; the MCL is not at risk. [Orthopedics. 2020;43(5):e399-e403.].
Assuntos
Artroscopia/métodos , Articulação do Cotovelo/cirurgia , Cotovelo/cirurgia , Cadáver , Dissecação , Humanos , Ligamentos Articulares/cirurgiaRESUMO
Background: Scaphoid fractures progress to nonunion rates of up to 15% when non-displaced, and are even more frequent when the fracture is displaced. Standard treatment in these cases is surgery; however, individuals unable to undergo this operation, or for those who wish to try more conservative measures, there may be benefit from nonoperative options. Of these, low-intensity pulsed ultrasound (LIPUS) has been shown to improve fracture nonunion healing. The purpose of this study was to perform a comprehensive meta-analysis of relevant literature to determine success of the use of LIPUS for treatment of scaphoid nonunion. Methods: Utilizing PubMed, Embase, and Ovid databases, we performed a literature search using key terms for scaphoid nonunions. A total of 686 studies met initial search criteria. Studies reporting fewer than 5 cases, those not published in English, those not related to LIPUS nonoperative scaphoid nonunion treatment, and those without sufficient data were excluded. Five studies met these criteria, and statistical analysis was performed to determine overall union rates. Results: The use of LIPUS on 166 nonunions reported a mean healing index of 78.6%. The average time to union following LIPUS treatment was 4.2 months. Conclusions: While surgical intervention is still the standard, our results show that LIPUS may serve as a nonoperative alternative to scaphoid nonunion in certain cases. The results are encouraging in which these challenging fracture a nonunions can heal without further surgical intervention in the majority of patients.
RESUMO
The pannexin family of channels consists of three members-pannexin-1 (Panx1), pannexin-2 (Panx2), and pannexin-3 (Panx3) that enable the exchange of metabolites and signaling molecules between intracellular and extracellular compartments. Pannexin-mediated release of intracellular ATP into the extracellular space has been tied to a number of cellular activities, primarily through the activity of type P2 purinergic receptors. Previous work indicates that the opening of Panx1 channels and activation of purinergic receptors by extracellular ATP may cause inflammation and apoptosis. In the CNS (central nervous system) and PNS (peripheral nervous system), coupled pannexin, and P2 functions have been linked to peripheral sensitization (pain) pathways. Purinergic pathways are also essential for other critical processes in the PNS, including myelination and neurite outgrowth. However, whether such pathways are pannexin-dependent remains to be determined. In this study, we use a Panx1 knockout mouse model and pharmacological inhibitors of the Panx1 and the ATP-mediated signaling pathway to fill gaps in our understanding of Panx1 localization in peripheral nerves, roles for Panx1 in axonal outgrowth and myelination, and neurite extension. Our data show that Panx1 is localized to axonal, myelin, and vascular compartments of the peripheral nerves. Knockout of Panx1 gene significantly increased axonal caliber in vivo and axonal growth rate in cultured dorsal root ganglia (DRG) neurons. Furthermore, genetic knockout of Panx1 or inhibition of components of purinergic signaling, by treatment with probenecid and apyrase, resulted in denser axonal outgrowth from cultured DRG explants compared to untreated wild-types. Our findings suggest that Panx1 regulates axonal growth in the peripheral nervous system.
RESUMO
The genome sequence of the obligate chemolithoautotroph Hydrogenovibrio crunogenus paradoxically predicts a complete oxidative citric acid cycle (CAC). This prediction was tested by multiple approaches including whole cell carbon assimilation to verify obligate autotrophy, phylogenetic analysis of CAC enzyme sequences and enzyme assays. Hydrogenovibrio crunogenus did not assimilate any of the organic compounds provided (acetate, succinate, glucose, yeast extract, tryptone). Enzyme activities confirmed that its CAC is mostly uncoupled from the NADH pool. 2-Oxoglutarate:ferredoxin oxidoreductase activity is absent, though pyruvate:ferredoxin oxidoreductase is present, indicating that sequence-based predictions of substrate for this oxidoreductase were incorrect, and that H. crunogenus may have an incomplete CAC. Though the H. crunogenus CAC genes encode uncommon enzymes, the taxonomic distribution of their top matches suggests that they were not horizontally acquired. Comparison of H. crunogenus CAC genes to those present in other 'Proteobacteria' reveals that H. crunogenus and other obligate autotrophs lack the functional redundancy for the steps of the CAC typical for facultative autotrophs and heterotrophs, providing another possible mechanism for obligate autotrophy.
Assuntos
Carbono/metabolismo , Ciclo do Ácido Cítrico , Fontes Hidrotermais/microbiologia , Piscirickettsiaceae/metabolismo , Crescimento Quimioautotrófico , Glucose/metabolismo , Oxirredução , Filogenia , Piscirickettsiaceae/classificação , Piscirickettsiaceae/genética , Ácido Pirúvico/metabolismoRESUMO
OBJECTIVES: A protocol using transthoracic echocardiography was designed to diagnose the common malfunctions of patients on chronic support with a left ventricular assist device (LVAD). BACKGROUND: Mechanical circulatory support, primarily with a LVAD, is increasingly used for treatment of advanced heart failure as a bridge to transplant and for long-term treatment of heart failure. The LVAD dysfunction is a recognized complication. To date, no studies have defined the role of transthoracic echocardiography in evaluating long-term mechanical complications of chronic LVAD support. METHODS: Transthoracic echocardiography was used in a protocol designed to detect the common types of mechanical malfunction. Patients were followed up with serial echocardiograms, and clinical validations were made with findings from a catheter-based protocol and inspection at the time of cardiac transplant or corrective surgery. RESULTS: Thirty-two patients with 44 LVADs were followed up during a four-year period using this protocol that correctly identified 11 patients with inflow valve regurgitation, 2 with intermittent inflow conduit obstruction, 1 with severe kinking of the outflow graft, and 9 with new insufficiency of the native aortic valve. CONCLUSIONS: As LVAD use for end-stage heart failure becomes widespread, and durations of support are extended, dysfunction will be increasingly prevalent. Transthoracic echocardiography provides a practical method to accurately identify the causes of mechanical dysfunction with patients on chronic LVAD support.
Assuntos
Ecocardiografia Transesofagiana , Insuficiência Cardíaca/terapia , Coração Auxiliar , Adulto , Idoso , Falha de Equipamento , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: A protocol was designed to diagnose the common malfunctions of a left ventricular assist device (LVAD). BACKGROUND: Mechanical circulatory support, primarily with an LVAD, is increasingly used for treatment of advanced heart failure (HF). Left ventricular assist device dysfunction is a recognized complication; but heretofore, a systematic method to accurately diagnose LVAD dysfunction has not been thoroughly described. METHODS: We developed a catheter-based protocol designed to characterize a normally functioning LVAD and diagnose multiple types of dysfunction. A total of 15 studies of 10 patients supported with an LVAD were reviewed. All patients had been evaluated due to concerns regarding LVAD dysfunction. RESULTS: Of 15 examinations performed, 11 documented severe LVAD inflow valve regurgitation. One of these cases proved to have coexistent severe mitral valve regurgitation. One case was diagnosed with distortion of the LVAD outflow graft. One case of suspected embolization from the pumping chamber excluded the outflow graft as the source of emboli. One study had aortic insufficiency. CONCLUSIONS: As LVAD use for treatment of end-stage HF becomes widespread and durations of support are extended, dysfunction will be increasingly prevalent. This catheter-based protocol provided a practical method to diagnose multiple causes of LVAD dysfunction.
Assuntos
Ventrículos do Coração/cirurgia , Coração Auxiliar , Adulto , Idoso , Insuficiência da Valva Aórtica/diagnóstico , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/etiologia , Estenose da Valva Aórtica/fisiopatologia , Débito Cardíaco/fisiologia , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/cirurgia , Angiografia Coronária , Circulação Coronária/fisiologia , Ecocardiografia Doppler , Eletrocardiografia , Desenho de Equipamento , Falha de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Isquemia Miocárdica/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Pressão Propulsora Pulmonar/fisiologia , Estatística como Assunto , Tromboembolia/diagnóstico , Tromboembolia/etiologia , Tromboembolia/fisiopatologiaRESUMO
CONTEXT: Dilated cardiomyopathy (DCM), a genetically heterogeneous disorder, causes heart failure and rhythm disturbances. The majority of identified DCM genes encode structural proteins of the contractile apparatus and cytoskeleton. Recently, genetic defects in calcium and potassium regulation have been discovered in patients with DCM, implicating an alternative disease mechanism. The full spectrum of genetic defects in DCM, however, has not been established. OBJECTIVES: To identify a novel gene for DCM at a previously mapped locus, define the spectrum of mutations in this gene within a DCM cohort, and determine the frequency of DCM among relatives inheriting a mutation in this gene. DESIGN, SETTING, AND PARTICIPANTS: Refined mapping of a DCM locus on chromosome 3p in a multigenerational family and mutation scanning in 156 unrelated probands with DCM, prospectively identified at the Mayo Clinic between 1987 and 2004. Relatives underwent screening echocardiography and electrocardiography and DNA sample procurement. MAIN OUTCOME MEASURE: Correlation of identified mutations with cardiac phenotype. RESULTS: Refined locus mapping revealed SCN5A, encoding the cardiac sodium channel, as a candidate gene. Mutation scans identified a missense mutation (D1275N) that cosegregated with an age-dependent, variably expressed phenotype of DCM, atrial fibrillation, impaired automaticity, and conduction delay. In the DCM cohort, additional missense (T220I, R814W, D1595H) and truncation (2550-2551insTG) SCN5A mutations, segregating with cardiac disease or arising de novo, were discovered in unrelated probands. Among individuals with an SCN5A mutation 27% had early features of DCM (mean age at diagnosis, 20.3 years), 38% had DCM (mean age at diagnosis, 47.9 years), and 43% had atrial fibrillation (mean age at diagnosis, 27.8 years). CONCLUSIONS: Heritable SCN5A defects are associated with susceptibility to early-onset DCM and atrial fibrillation. Similar or even identical mutations may lead to heart failure, arrhythmia, or both.
Assuntos
Fibrilação Atrial/genética , Cardiomiopatia Dilatada/genética , Canais de Sódio/genética , Adulto , Cromossomos Humanos Par 3/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Canal de Sódio Disparado por Voltagem NAV1.5 , Linhagem , Fenótipo , Fatores de RiscoRESUMO
PURPOSE: Reverse total shoulder arthroplasty (RTSA) may be used to treat a variety of pathologic shoulder conditions, but complications such as scapular notching continue raise concerns. Variable anatomy surrounding the glenoid may have implications for future RTSA design, but at present the anatomy of the scapular neck in the human population has not been clearly defined. MATERIALS AND METHODS: 442 human scapulae from the Hamann-Todd Osteological Collection were measured for scapular neck length (SNL) and scapular neck angle (SNA). SNL was defined as the distance from the most lateral portion of the infraglenoid tubercle to the most inferolateral portion of the glenoid fossa. The SNA was measured according to Gerber et al. previously. The mean, standard deviation and ranges for SNL and SNA were calculated and compared based on sex and race, and interobserver variability was calculated. RESULTS: The mean SNL was 1.06 cm ± 0.33 cm (0.37-2.43 cm). Males demonstrated a larger SNL (1.08 cm ± 0.33 cm) than females (1.01 cm ± 0.32 cm) (P < 0.12), and Caucasians (1.09 cm ± 0.33 cm) demonstrated a significantly larger SNL than African-Americans (1.00 cm ± 0.32) (P < 0.01). The mean SNA was 106.7° ± 11.0° (76.9-139.4°). No significant correlation was found between SNL and SNA (Pearson Correlation Coefficient = 0.018) (P < 0.702). CONCLUSION: Scapular neck length and SNA vary widely within the population but there appears to be a tendency towards increased SNL in males and Caucasians. CLINICAL RELEVANCE: The anatomy of the scapular neck may have significant implications for RTSA design, surgical planning, and reduction of associated complications.
RESUMO
Acute osmotic fluctuations in the brain occur during a number of clinical conditions and can result in a variety of adverse neurological symptoms. Osmotic perturbation can cause changes in the volumes of intra- and extracellular fluid and, due to the rigidity of the skull, can alter intracranial pressure thus making it difficult to analyze purely osmotic effects in vivo. The present study aims to determine the effects of changes in osmolarity on SH-SY5Y human neuroblastoma cells in vitro, and the role of the actin-myosin network in regulating this response. Cells were exposed to hyper- or hypoosmotic media and morphological and cytoskeletal responses were recorded. Hyperosmotic shock resulted in a drop in cell body volume and planar area, a persisting shape deformation, and increases in cellular translocation. Hypoosmotic shock did not significantly alter planar area, but caused a transient increase in cell body volume and an increase in cellular translocation via the development of small protrusions rich in actin. Disruption of the actin-myosin network with latrunculin and blebbistatin resulted in changes to volume and shape regulation, and a decrease in cellular translocation. In both osmotic perturbations, no apparent disruptions to cytoskeletal integrity were observed by light microscopy. Overall, because osmotically induced changes persisted even after volume regulation occurred, it is possible that osmotic stress may play a larger role in neurological dysfunction than currently believed.
Assuntos
Actinas/metabolismo , Forma Celular/fisiologia , Citoesqueleto/metabolismo , Miosinas/metabolismo , Neurônios/metabolismo , Pressão Osmótica/fisiologia , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Pressão Osmótica/efeitos dos fármacosRESUMO
Valvular calcification is a common consequence of systemic calcium deposition resulting from chronic renal failure. Thrombi can form on such vascular calcifications and embolize to the cerebral, myocardial, and mesenteric vasculature with devastating consequences. We report the unique case of a patient with myocardial and cerebrovascular ischemia resulting from emboli arising from a massive mitral annular calcification.