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1.
Nature ; 624(7991): 403-414, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38092914

RESUMO

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for 'gain setting' of brain-spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.


Assuntos
Encéfalo , Perfilação da Expressão Gênica , Vias Neurais , Neurônios , Medula Espinal , Animais , Camundongos , Hipotálamo , Neurônios/metabolismo , Neuropeptídeos , Medula Espinal/citologia , Medula Espinal/metabolismo , Encéfalo/citologia , Encéfalo/metabolismo , Neurotransmissores , Mesencéfalo/citologia , Formação Reticular/citologia , Eletrofisiologia , Cerebelo/citologia , Córtex Cerebral/citologia
2.
Clin Infect Dis ; 78(4): 949-955, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38330243

RESUMO

BACKGROUND: Since publication of Duke criteria for infective endocarditis (IE) diagnosis, several modifications have been proposed. We aimed to evaluate the diagnostic performance of the Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) 2023 criteria compared to prior versions from 2000 (Duke-Li 2000) and 2015 (Duke-ESC [European Society for Cardiology] 2015). METHODS: This study was conducted at 2 university hospitals between 2014 and 2022 among patients with suspected IE. A case was classified as IE (final IE diagnosis) by the Endocarditis Team. Sensitivity for each version of the Duke criteria was calculated among patients with confirmed IE based on pathological, surgical, and microbiological data. Specificity for each version of the Duke criteria was calculated among patients with suspected IE for whom IE diagnosis was ruled out. RESULTS: In total, 2132 episodes with suspected IE were included, of which 1101 (52%) had final IE diagnosis. Definite IE by pathologic criteria was found in 285 (13%), 285 (13%), and 345 (16%) patients using the Duke-Li 2000, Duke-ESC 2015, or the Duke-ISCVID 2023 criteria, respectively. IE was excluded by histopathology in 25 (1%) patients. The Duke-ISCVID 2023 clinical criteria showed a higher sensitivity (84%) compared to previous versions (70%). However, specificity of the new clinical criteria was lower (60%) compared to previous versions (74%). CONCLUSIONS: The Duke-ISCVID 2023 criteria led to an increase in sensitivity compared to previous versions. Further studies are needed to evaluate items that could increase sensitivity by reducing the number of IE patients misclassified as possible, but without having detrimental effect on specificity of Duke criteria.


Assuntos
Doenças Transmissíveis , Endocardite Bacteriana , Endocardite , Próteses Valvulares Cardíacas , Humanos , Endocardite Bacteriana/diagnóstico , Endocardite/diagnóstico , Próteses Valvulares Cardíacas/microbiologia , Fluordesoxiglucose F18
3.
Clin Infect Dis ; 78(3): 655-662, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38168726

RESUMO

BACKGROUND: The Duke criteria for infective endocarditis (IE) diagnosis underwent revisions in 2023 by the European Society of Cardiology (ESC) and the International Society for Cardiovascular Infectious Diseases (ISCVID). This study aims to assess the diagnostic accuracy of these criteria, focusing on patients with Staphylococcus aureus bacteremia (SAB). METHODS: This Swiss multicenter study conducted between 2014 and 2023 pooled data from three cohorts. It evaluated the performance of each iteration of the Duke criteria by assessing the degree of concordance between definite S. aureus IE (SAIE) and the diagnoses made by the Endocarditis Team (2018-23) or IE expert clinicians (2014-17). RESULTS: Among 1344 SAB episodes analyzed, 486 (36%) were identified as cases of SAIE. The 2023 Duke-ISCVID and 2023 Duke-ESC criteria demonstrated improved sensitivity for SAIE diagnosis (81% and 82%, respectively) compared to the 2015 Duke-ESC criteria (75%). However, the new criteria exhibited reduced specificity for SAIE (96% for both) compared to the 2015 criteria (99%). Spondylodiscitis was more prevalent among patients with SAIE compared to those with SAB alone (10% vs 7%, P = .026). However, when patients meeting the minor 2015 Duke-ESC vascular criterion were excluded, the incidence of spondylodiscitis was similar between SAIE and SAB patients (6% vs 5%, P = .461). CONCLUSIONS: The 2023 Duke-ISCVID and 2023 Duke-ESC clinical criteria show improved sensitivity for SAIE diagnosis compared to 2015 Duke-ESC criteria. However, this increase in sensitivity comes at the expense of reduced specificity. Future research should aim at evaluating the impact of each component introduced within these criteria.


Assuntos
Bacteriemia , Cardiologia , Discite , Endocardite Bacteriana , Endocardite , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/epidemiologia , Endocardite/diagnóstico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Bacteriemia/diagnóstico , Bacteriemia/epidemiologia
4.
J Nucl Cardiol ; 36: 101865, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38679286

RESUMO

BACKGROUND: To identify 18F-fluorodeoxyglucose (FDG) uptake patterns in positron emission tomography/computed tomography (PET/CT) caused by infection, inflammation, surgical material, and/or graft coating. METHODS AND RESULTS: Of 610 consecutive patients with thoracic aortic graft surgery, 60 patients with 187 PET/CT were retrospectively included. We quantified FDG uptake in all grafts using maximum standardized uptake value (SUVmax) alone and in relation to liver background (SUVratio) and determined the uptake pattern. Mixed linear regression models with random slope and intercept were applied for the analysis of SUVratio over time and generalized estimating equations to analyze the associations with anastomosis uptake. FDG uptake was frequently focal (90%), higher in infected than in noninfected grafts (mean SUVratio 2.19; 95% CI 2.05-2.32 vs. 1.63; 1.46-1.79, P < 0.001), and decreasing slowly over time (SUVratio per year since surgery -0.048; 95% CI -0.15- 0.051, P = 0.34), without a difference in slope between infected and noninfected grafts (P = 0.52). There was no evidence of an interaction between SUVratio and use of BioGlue® surgical adhesive (intercept P = 0.73, slope P = 0.71), or graft coating (gelatin and collagen, all P > 0.7). FDG uptake at the anastomosis was more frequent in noninfected grafts than in infected grafts (66% vs. 21%, odds ratio (OR) 11.34; 95% CI 3.61-35.66, P < 0.001). This effect was attenuated by the use of BioGlue® (OR 5.05; 95% CI 0.45-56.9, P = 0.19). CONCLUSIONS: FDG uptake in PET/CT after thoracic aortic graft surgery is higher in infected grafts than in noninfected grafts. In noninfected grafts, focal uptake is also frequent, mostly anastomosis-associated, not associated with graft coating, and possibly affected by the use of BioGlue®.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Fluordesoxiglucose F18/farmacocinética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Compostos Radiofarmacêuticos/farmacocinética , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Inflamação/diagnóstico por imagem , Infecções Relacionadas à Prótese/diagnóstico por imagem , Prótese Vascular/efeitos adversos , Aorta Torácica/diagnóstico por imagem , Dissecção da Aorta Torácica
5.
Infection ; 51(1): 47-59, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35972680

RESUMO

PURPOSE: Infective endocarditis (IE) is a severe bacterial infection. As a measure of prevention, the administration of antibiotic prophylaxis (AP) prior to dental procedures was recommended in the past. However, between 2007 and 2009, guidelines for IE prophylaxis changed all around the word, limiting or supporting the complete cessation of AP. It remains unclear whether AP is effective or not against IE. METHODS: We conducted a systematic review whether the administration of AP in adults before any dental procedure, compared to the non-administration of such drugs, has an effect on the risk of developing IE. We searched for studies in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via OVID, and EMBASE. Two different authors filtered articles independently and data extraction was performed based on a pre-defined protocol. RESULTS: The only cohort study meeting our criteria included patients at high-risk of IE. Analysis of the extracted data showed a non-significant decrease in the risk of IE when high-risk patients take AP prior to invasive dental procedures (RR 0.39, p-value 0.11). We did not find other studies including patients at low or moderate risk of IE. Qualitative evaluation of the excluded articles reveals diversity of results and suggests that most of the state-of-the-art articles are underpowered. CONCLUSIONS: Evidence to support or discourage the use of AP prior to dental procedures as a prevention for IE is very low. New high-quality studies are needed, even though such studies would require big settings and might not be immediately feasible.


Assuntos
Endocardite Bacteriana , Endocardite , Adulto , Humanos , Antibioticoprofilaxia , Estudos de Coortes , Endocardite Bacteriana/prevenção & controle , Endocardite/prevenção & controle , Odontologia
6.
Heart Fail Clin ; 17(4): 697-708, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34511216

RESUMO

Heart transplantation (HTx) is the treatment of choice in patients with late-stage advanced heart failure (Advanced HF). Survival rates 1, 5, and 10 years after transplantation are 87%, 77%, and 57%, respectively, and the average life expectancy is 9.16 years. However, because of the donor organ shortage, waiting times often exceed life expectancy, resulting in a waiting list mortality of around 20%. This review aims to provide an overview of current standard, recent advances, and future developments in the treatment of Advanced HF with a focus on long-term mechanical circulatory support and HTx.


Assuntos
Sistema Cardiovascular , Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Insuficiência Cardíaca/terapia , Humanos , Resultado do Tratamento , Listas de Espera
7.
Proc Natl Acad Sci U S A ; 111(7): 2776-81, 2014 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-24550307

RESUMO

The nematode Caenorhabditis elegans navigates toward a preferred temperature setpoint (Ts) determined by long-term temperature exposure. During thermotaxis, the worm migrates down temperature gradients at temperatures above Ts (negative thermotaxis) and performs isothermal tracking near Ts. Under some conditions, the worm migrates up temperature gradients below Ts (positive thermotaxis). Here, we analyze positive and negative thermotaxis toward Ts to study the role of specific neurons that have been proposed to be involved in thermotaxis using genetic ablation, behavioral tracking, and calcium imaging. We find differences in the strategies for positive and negative thermotaxis. Negative thermotaxis is achieved through biasing the frequency of reorientation maneuvers (turns and reversal turns) and biasing the direction of reorientation maneuvers toward colder temperatures. Positive thermotaxis, in contrast, biases only the direction of reorientation maneuvers toward warmer temperatures. We find that the AFD thermosensory neuron drives both positive and negative thermotaxis. The AIY interneuron, which is postsynaptic to AFD, may mediate the switch from negative to positive thermotaxis below Ts. We propose that multiple thermotactic behaviors, each defined by a distinct set of sensorimotor transformations, emanate from the AFD thermosensory neurons. AFD learns and stores the memory of preferred temperatures, detects temperature gradients, and drives the appropriate thermotactic behavior in each temperature regime by the flexible use of downstream circuits.


Assuntos
Caenorhabditis elegans/fisiologia , Memória de Longo Prazo/fisiologia , Modelos Neurológicos , Movimento/fisiologia , Neurônios/fisiologia , Sensação Térmica/fisiologia , Animais , Temperatura
8.
Eur Heart J ; 36(40): 2745-53, 2015 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-26188001

RESUMO

AIMS: We identified 10 patients with disseminated Mycobacterium chimaera infections subsequent to open-heart surgery at three European Hospitals. Infections originated from the heater-cooler unit of the heart-lung machine. Here we describe clinical aspects and treatment course of this novel clinical entity. METHODS AND RESULTS: Interdisciplinary care and follow-up of all patients was documented by the study team. Patients' characteristics, clinical manifestations, microbiological findings, and therapeutic measures including surgical reinterventions were reviewed and treatment outcomes are described. The 10 patients comprise a 1-year-old child and nine adults with a median age of 61 years (range 36-76 years). The median duration from cardiac surgery to diagnosis was 21 (range 5-40) months. All patients had prosthetic material-associated infections with either prosthetic valve endocarditis, aortic graft infection, myocarditis, or infection of the prosthetic material following banding of the pulmonary artery. Extracardiac manifestations preceded cardiovascular disease in some cases. Despite targeted antimicrobial therapy, M. chimaera infection required cardiosurgical reinterventions in eight patients. Six out of 10 patients experienced breakthrough infections, of which four were fatal. Three patients are in a post-treatment monitoring period. CONCLUSION: Healthcare-associated infections due to M. chimaera occurred in patients subsequent to cardiac surgery with extracorporeal circulation and implantation of prosthetic material. Infections became clinically apparent after a time lag of months to years. Mycobacterium chimaera infections are easily missed by routine bacterial diagnostics and outcome is poor despite long-term antimycobacterial therapy, probably because biofilm formation hinders eradication of pathogens.


Assuntos
Ponte de Artéria Coronária/efeitos adversos , Infecção Hospitalar/etiologia , Endocardite Bacteriana/etiologia , Próteses Valvulares Cardíacas/efeitos adversos , Infecções por Mycobacterium não Tuberculosas/etiologia , Infecções Relacionadas à Prótese/etiologia , Adulto , Idoso , Valva Aórtica/cirurgia , Contaminação de Equipamentos , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade
9.
Acta Cardiol ; 70(6): 665-71, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26717214

RESUMO

OBJECTIVE: The objective of this study was assess robot-assisted gait therapy with the Lokomat® system in heart failure patients. METHODS: Patients (n = 5) with stable heart failure and a left ventricular ejection fraction of less than 45% completed a four-week aerobic training period with three trainings per week and an integrated dynamic resistance training of the lower limbs. Patients underwent testing of cardiac and inflammatory biomarkers. A cardiopulmonary exercise test, a quality of life score and an evaluation of the muscular strength by measuring the peak quadriceps force was performed. RESULTS: No adverse events occurred. The combined training resulted in an improvement in peak work rate (range: 6% to 36%) and peak quadriceps force (range: 3% to 80%) in all participants. Peak oxygen consumption (range: ­3% to + 61%) increased in three, and oxygen pulse (range: ­7% to + 44%) in four of five patients. The quality of life assessment indicated better well-being in all participants. NT-ProBNP (+233 to ­733 ng/ml) and the inflammatory biomarkers (hsCRP and IL6) decreased in four of five patients (IL 6: +0.5 to ­2 mg/l, hsCRP: +0.2 to ­6.5 mg/l). CONCLUSIONS: Robot-assisted gait therapy with the Lokomat® System is feasible in heart failure patients and was safe in this trial. The combined aerobic and resistance training intervention with augmented feedback resulted in benefits in exercise capacity, muscle strength and quality of life, as well as an improvement of cardiac (NT-ProBNP) and inflammatory (IL6, hsCRP) biomarkers. Results can only be considered as preliminary and need further validation in larger studies. (ClinicalTrials.gov number, NCT 02146196)


Assuntos
Terapia por Exercício/métodos , Tolerância ao Exercício/fisiologia , Marcha/fisiologia , Insuficiência Cardíaca/reabilitação , Treinamento Resistido/métodos , Robótica/métodos , Função Ventricular Esquerda , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Consumo de Oxigênio/fisiologia , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento
10.
BMC Cardiovasc Disord ; 14: 81, 2014 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-25004927

RESUMO

BACKGROUND: As coronary computed tomography angiography (CCTA) has emerged as a non-invasive alternative for evaluation of coronary anatomy with a lower referral threshold than invasive coronary angiography (ICA), the prevalence of coronary anomalies in CCTA may more closely reflect the true prevalence in the general population. Morphological features of coronary anomalies can be evaluated more precisely by CCTA than by ICA, which might lead to a higher identification of congenital coronary anomalies in CCTA compared to ICA.To evaluate the incidence, clinical and morphological features of the anatomy of patients with coronary anomalies detected either by coronary computed tomography angiography (CCTA) with prospective ECG-triggering or invasive coronary angiography (ICA). METHODS: Consecutive patients underwent 64-slice CCTA (n = 1'759) with prospective ECG-triggering or ICA (n = 9'782) and coronary anatomy was evaluated for identification of coronary anomalies to predefined criteria (origin, course and termination) according to international recommendations. RESULTS: The prevalence of coronary anomalies was 7.9% (n = 138) in CCTA and 2.1% in ICA (n = 203; p < 0.01). The most commonly coronary anomaly detected by CCTA was myocardial bridging 42.8% (n = 59) vs. 21.2% (n = 43); p < 0.01, while with ICA an absent left main trunk was the most observed anomaly 36.0% (n = 73; p < 0.01). In 9.4% (n = 13) of identified coronary anomalies in CCTA 9.4% were potentially serious coronary anaomalies, defined as a course of the coronary artery between aorta and pulmonary artery were identified. CONCLUSION: The prevalence of coronary anomalies is substantially higher with CCTA than ICA even after exclusion of patients with myocardial bridging which is more frequently found with CCTA. This suggests that the true prevalence of coronary anomalies in the general population may have been underestimated based on ICA.


Assuntos
Angiografia Coronária/métodos , Anomalias dos Vasos Coronários/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas de Imagem de Sincronização Cardíaca , Anomalias dos Vasos Coronários/epidemiologia , Eletrocardiografia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Doses de Radiação , Sistema de Registros , Estudos Retrospectivos , Suíça/epidemiologia
11.
Circulation ; 126(4): 440-7, 2012 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-22761452

RESUMO

BACKGROUND: Although newer immunosuppressive agents, such as mTOR (mammalian target of rapamycin) inhibitors, have lowered the occurrence of malignancies after transplantation, cancer is still a leading cause of death late after heart transplantation. Statins may have an impact on clinical outcomes beyond their lipid-lowering effects. The aim of the present study was to delineate whether statin therapy has an impact on cancer risk and total mortality after heart transplantation. METHODS AND RESULTS: A total of 255 patients who underwent heart transplantation at the University Hospital Zurich between 1985 and 2007 and survived the first year were included in the present study. The primary outcome measure was the occurrence of any malignancy; the secondary end point was overall survival. During follow-up, a malignancy was diagnosed in 108 patients (42%). The cumulative incidence of tumors 8 years after transplantation was reduced in patients receiving a statin (34% versus 13%; 95% confidence interval, 0.25-0.43 versus 0.07-0.18; P<0.003). Statin use was associated with improved cancer-free and overall survival (both P<0.0001). A Cox regression model that analyzed the time to tumor formation with or without statin therapy, adjusted for age, male sex, type of cardiomyopathy, and immunosuppressive therapy (including switch to mTOR inhibitors or tacrolimus), demonstrated a superior survival in the statin group. Statins reduced the hazard of occurrence of any malignancy by 67% (hazard ratio, 0.33; 95% confidence interval, 0.21-0.51; P<0.0001). CONCLUSIONS: Although it is not possible to adjust for all potential confounders because of the very long follow-up period, this registry suggests that statin use is associated with improved cancer-free and overall survival after cardiac transplantation. These data will need to be confirmed in a prospective trial.


Assuntos
Transplante de Coração , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/imunologia , Transplante de Coração/mortalidade , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Tacrolimo/uso terapêutico
12.
Child Obes ; 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37971786

RESUMO

Background: Factors related to clinically meaningful outcomes for pediatric patients seeking care for severe obesity are not well known. Examining patient-level and program-level characteristics related to success may inform future care. Objectives: To determine factors associated with a clinically significant reduction in weight status measured by %BMIp95 after 6 months of treatment. Study Design: This is a retrospective study of youth 5-17 years of age seeking multicomponent weight management care to determine if patient characteristics, treatment recommendations, reported adherence, and additional program-affiliated class participation are associated with 6-month change in %BMIp95. Results: Among 170 children with obesity, higher reductions in %BMIp95 were seen in those with medium-high dietary adherence compared to low-none (-10.8 vs. -4.0, p = 0.002). Post hoc analysis showed higher dietary adherence among those with private insurance than public insurance (59% vs. 41%, respectively, p = 0.04). Conclusion: Children receiving multidisciplinary multicomponent weight management, who achieve clinically meaningful outcomes, are more likely to be adherent to dietary recommendations regardless of the type. Further study is needed of how best to address social determinants of health to improve dietary adherence. Clinical Trial Registration Number: NCT02121132.

13.
Elife ; 122023 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-36876911

RESUMO

Brainstem olivocochlear neurons (OCNs) modulate the earliest stages of auditory processing through feedback projections to the cochlea and have been shown to influence hearing and protect the ear from sound-induced damage. Here, we used single-nucleus sequencing, anatomical reconstructions, and electrophysiology to characterize murine OCNs during postnatal development, in mature animals, and after sound exposure. We identified markers for known medial (MOC) and lateral (LOC) OCN subtypes, and show that they express distinct cohorts of physiologically relevant genes that change over development. In addition, we discovered a neuropeptide-enriched LOC subtype that produces Neuropeptide Y along with other neurotransmitters. Throughout the cochlea, both LOC subtypes extend arborizations over wide frequency domains. Moreover, LOC neuropeptide expression is strongly upregulated days after acoustic trauma, potentially providing a sustained protective signal to the cochlea. OCNs are therefore poised to have diffuse, dynamic effects on early auditory processing over timescales ranging from milliseconds to days.


Just as our pupils dilate or shrink depending on the amount of light available to our eyes, our ears adjust their sensitivity based on the sound environment we encounter. Evidence suggests that a group of cells known as olivocochlear neurons (OCNs for short) may be involved in this process. These cells are located in the brainstem but project into the cochlea, the inner ear structure that converts sound waves into the electrical impulses relayed to the brain. OCNs may mediate how sounds are detected and encoded "at the source." Historically, OCNs have been divided into two groups (medial or lateral OCNs) based on different morphologies and roles in hearing. For instance, medial OCNs are thought to protect our ears against loud sounds by sending molecular signals to the inner ear cells that amplify certain auditory signals. However, it remains difficult to disentangle the precise function of the different types of OCNs, in part because scientists still lack markers that would allow them to distinguish between medial and lateral cells simply based on genetic activity. Frank et al. aimed to eliminate this bottleneck by identifying which genes were switched on and to what degree in individual mouse medial and lateral OCNs; this was done throughout development and after exposure to loud noises. The experiments uncovered a range of genetic markers for medial and lateral OCNs, showing that these cells switch on different sets of genes relevant to their role over development. This gene expression data also revealed that two distinct groups of lateral OCNs exist, one of which is characterised by the production of large amounts of neuropeptides, a type of chemical messenger that can modulate neural circuit activity. Further work in both developing and adult mice showed that this production is shaped by the activity of the cells, with the neuropeptide levels increasing when the animals are exposed to damaging levels of noise. This change lasts for several days, suggesting that such an experience can have long-lasting effects on how the brain provides feedback to the ear. Overall, the results by Frank et al. will help to better identify and characterize the different types of OCNs and the role that they have in hearing. By uncovering the chemical messengers that mediate the response to loud noises, this research may contribute to a better understanding of how to prevent or reduce hearing loss.


Assuntos
Perda Auditiva Provocada por Ruído , Núcleo Olivar , Camundongos , Animais , Núcleo Olivar/fisiologia , Retroalimentação , Audição/genética , Cóclea/fisiologia
14.
Front Cardiovasc Med ; 10: 1223878, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37692048

RESUMO

Introduction: Around 25% of patients with left-sided infective endocarditis and operative indication do not undergo surgery. Baseline characteristics and outcomes are underreported. This study describes characteristics and outcomes of surgical candidates with surgical intervention or medical treatment only. Methods: Retrospective analysis of ongoing collected data from a single-center from an observational cohort of patients with infective endocarditis (ENVALVE). Kaplan-Meier estimates for survival was calculated. Factors associated with survival were assessed using a bivariable Cox model. To adjust for confounding by indication, uni- and multivariable logistic regression for the propensity to receive surgery were adjusted. Results: From January 2018 and December 2021, 154 patients were analyzed: 116 underwent surgery and 38 received medical treatment only. Surgical candidates without surgery were older (70 vs. 62 years, p = 0.001). They had higher preoperative risk profile (EuroSCORE II 14% (7.2-28.6) vs. 5.8% (2.5-20.3), p = 0.002) and more comorbidities. One patient was lost-to-follow-up. Survival analysis revealed a significant higher one-year survival rate among patients following surgery (83.7% vs. 15.3% in the non-surgical group; log-rank test <0.0001). In the final multivariable adjusted model, surgery was less likely among patients with liver cirrhosis [OR = 0.03 (95% CI 0.00-0.30)] and with hemodialysis [OR = 0.014 (95% CI 0.00-0.47)]. Conclusion: Patients with left-sided infective endocarditis who do not undergo surgery despite an operative indication are older, have more comorbidities and therefore higher preoperative risk profile and a low 1-year survival. The role of the Endocarditis Team may be particularly important for the decision-making process in this specific group.

15.
Swiss Med Wkly ; 152: 40012, 2022 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-36534966

RESUMO

AIMS OF THE STUDY: Numerous studies from different countries have contributed to an improved understanding of blood culture-negative infective endocarditis. However, little is known about its epidemiology and microbiology in Switzerland. We aimed to assess the epidemiology and microbiology of blood culture-negative endocarditis at the University Hospital Zurich, Switzerland. METHODS: We screened all patients hospitalised between 1997 and 2020 with possible or definite endocarditis at our institution. Thereof, we identified all cases with blood culture-negative endocarditis and retrospectively retrieved patient characteristics, microbiological, histopathological, radiographic and surgical data from medical records. RESULTS: Among 861 patients screened, 66 (7.7%) cases of blood culture-negative endocarditis were identified. Thereof, 31 cases could be microbiologically documented or not documented (n = 30), and in five cases a non-infectious aetiology was confirmed. Endocarditis predominantly affected men (77%) and the left heart (79%); predisposing factors were prosthetic valves (42%), congenital heart disease (35%) and prior endocarditis (14%). The most common reasons for negative blood cultures were antibiotic treatment prior to blood culture sampling (35%), fastidious and slow growing microorganisms (30%) and definite non-infective endocarditis (8%). Coxiella burnetii and Bartonella spp. were the most common fastidious bacteria identified. In addition to serology, identification of causative microorganisms was possible by microbiological and/or histopathological analysis of tissue samples, of which polymerase chain reaction testing (PCR) of the 16S ribosomal RNA proved to be most successful. CONCLUSIONS: The present study provides a detailed analysis of blood culture-negative endocarditis over a time span of more than 20 years in Zurich, Switzerland. Antibiotic treatment prior to blood collection, and fastidious and slow growing organisms were identified as main reasons for sterile blood cultures. Typical culture-negative bacteria were mainly found by PCR and/or culture of tissue samples.


Assuntos
Endocardite Bacteriana , Endocardite , Masculino , Humanos , Estudos Retrospectivos , Hemocultura , Centros de Atenção Terciária , Suíça , Endocardite Bacteriana/epidemiologia , Endocardite Bacteriana/microbiologia , Bactérias/genética , Antibacterianos
16.
Circ J ; 75(11): 2648-53, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21891968

RESUMO

BACKGROUND: Patients undergoing acute left main (LM) coronary artery revascularization have a high mortality and natriuretic peptides such as N-terminal pro-B-type (NT-proBNP) have been shown to have prognostic value in patients with acute coronary syndromes. The present study looked at the prognostic value of NT-proBNP in these patients. METHODS AND RESULTS: We studied all consecutive patients undergoing acute LM coronary artery percutaneous coronary intervention between January 2005 and December 2008 in whom NT-proBNP was measured (n=71). We analyzed the clinical characteristics and the short- and long-term outcomes in relation to NT-proBNP level at admission. Median NT-proBNP was 1,364 ng/L, ranging from 46 to 70,000 ng/L. NT-proBNP was elevated in 63 (89%) patients and was ≥1,000ng/L in 42 (59%). Log NT-proBNP (hazard ratio [HR] 3.51, 95% confidence interval [CI] 1.55-7.97, P=0.003) and left ventricular ejection fraction (HR 0.95, 95%CI 0.91-0.99, P=0.007) were predictors for all-cause mortality. Log NT-proBNP was the only independent significant predictor of cardiovascular mortality. In-hospital mortality was 0% for patients with NT-proBNP <1,000, but 17% for those with NT-proBNP ≥1,000 (P=0.036). CONCLUSIONS: NT-proBNP is a strong predictor of outcome in patients undergoing acute LM coronary artery stenting. Mortality in such patients is high, but those with NT-proBNP < 1,000ng/L may have a favorable short- and long-term prognosis. Further research, including a larger patient population, is needed to determine the optimal cut-off value for NT-proBNP in patients undergoing acute LM coronary artery intervention.


Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Angioplastia Coronária com Balão , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Taxa de Sobrevida , Fatores de Tempo
17.
Indian J Thorac Cardiovasc Surg ; 37(5): 573-576, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34511767

RESUMO

Fungal osteomyelitis is an uncommon complication after cardiac surgery and associated with high mortality. A case of Candida albicans and Staphylococcus epidermidis osteomyelitis with device infection after implantation of a left ventricular assist device in a 60-year-old male patient is presented here. After clinical identification and confirmation with microbiological examinations and fluorodeoxyglucose positron emission tomography (FDG-PET) scan, debridement was performed. Surgical specimens grew C. albicans and S. epidermidis. Fluconazole, daptomycin, and negative pressure wound therapy were initiated, but failed to achieve healing. Total sternectomy and pectoralis flap reconstruction were performed. There was no recurrent infection for C. albicans on a prolonged antifungal regime. The combination of antifungal therapy and aggressive surgical debridement may be useful to control fungal osteomyelitis.

18.
Swiss Med Wkly ; 151: w20473, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33705562

RESUMO

The Swiss societies of Infectious Diseases, Pediatric Cardiology and Cardiology and the Pediatric Infectious Disease Group of Switzerland present the current update on infective endocarditis prophylaxis in a joint initiative. The major focus of the revised recommendations is a comprehensive prevention campaign for all patients at risk for infective endocarditis. Antibiotic prophylaxis is recommended only for individuals at high risk. Within this high-risk group there is a ranking order, and the conditions are presented accordingly. Antibiotic prophylaxis is no longer recommended for patients with unrepaired ventricular septal defects and patent ductus arteriosus. Recommendations for antibiotic prophylaxis for the prevention of infective endocarditis are categorized in dental and non-dental interventions.


Assuntos
Endocardite Bacteriana , Endocardite , Antibioticoprofilaxia , Criança , Endocardite/prevenção & controle , Endocardite Bacteriana/prevenção & controle , Humanos , Suíça
20.
Card Fail Rev ; 5(3): 140-146, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31768270

RESUMO

The prognostic significance of the right ventricle (RV) has recently been recognised in several conditions, primarily those involving the left ventricle, the lungs and their vascular bed, or the right-sided chambers. Recent advances in imaging techniques have created new opportunities to study RV anatomy, physiology and pathophysiology, and contemporary research efforts have opened the doors to new treatment possibilities. Nevertheless, the treatment of RV failure remains challenging. Optimal management should consider the anatomical and physiological particularities of the RV and include appropriate imaging techniques to understand the underlying pathophysiological mechanisms. Treatment should include rapid optimisation of volume status, restoration of perfusion pressure and improvement of myocardial contractility and rhythm, and, in case of refractory RV failure, mechanical circulatory support.

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