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The appearance of coronavirus disease 2019 (COVID-19) and other emerging infections has significantly impacted the field of dentistry, leading to widespread changes in practices and protocols. This has included the implementation of strict infection control measures, such as meticulous use of personal protective equipment, minimizing aerosol-generating procedures, and the adoption of teledentistry to reduce in-person contact. To date, the complete impact of delays in dental care caused by lockdowns has yet to be determined. The challenges faced during the COVID-19 pandemic have propelled innovation, shaping a new era of dentistry focused on safety against novel and re-emerging infections.
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COVID-19 , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Equipamento de Proteção Individual , Odontologia , Controle de Infecções Dentárias/métodos , SARS-CoV-2 , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/epidemiologia , Assistência OdontológicaRESUMO
OBJECTIVES: This study compares the performance of the artificial intelligence (AI) platform Chat Generative Pre-Trained Transformer (ChatGPT) to Otolaryngology trainees on board-style exam questions. METHODS: We administered a set of 30 Otolaryngology board-style questions to medical students (MS) and Otolaryngology residents (OR). 31 MSs and 17 ORs completed the questionnaire. The same test was administered to ChatGPT version 3.5, five times. Comparisons of performance were achieved using a one-way ANOVA with Tukey Post Hoc test, along with a regression analysis to explore the relationship between education level and performance. RESULTS: The average scores increased each year from MS1 to PGY5. A one-way ANOVA revealed that ChatGPT outperformed trainee years MS1, MS2, and MS3 (p = <0.001, 0.003, and 0.019, respectively). PGY4 and PGY5 otolaryngology residents outperformed ChatGPT (p = 0.033 and 0.002, respectively). For years MS4, PGY1, PGY2, and PGY3 there was no statistical difference between trainee scores and ChatGPT (p = .104, .996, and 1.000, respectively). CONCLUSION: ChatGPT can outperform lower-level medical trainees on Otolaryngology board-style exam but still lacks the ability to outperform higher-level trainees. These questions primarily test rote memorization of medical facts; in contrast, the art of practicing medicine is predicated on the synthesis of complex presentations of disease and multilayered application of knowledge of the healing process. Given that upper-level trainees outperform ChatGPT, it is unlikely that ChatGPT, in its current form will provide significant clinical utility over an Otolaryngologist.
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Avaliação Educacional , Internato e Residência , Otolaringologia , Estudantes de Medicina , Humanos , Otolaringologia/educação , Avaliação Educacional/métodos , Inquéritos e Questionários , Inteligência Artificial , Competência ClínicaRESUMO
BACKGROUND: IgE to galactose-alpha-1,3-galactose (alpha-gal) is linked to tick bites and an important cause of anaphylaxis and urticarial reactions to mammalian meat. The alpha-gal syndrome (AGS) is recognized as being common in the southeastern United States. However, prevalence studies are lacking and open questions remain about risk factors and clinical presentation of alpha-gal sensitization. OBJECTIVE: Here we characterized the prevalence as well as the presentation and risk factors of AGS and alpha-gal IgE sensitization in adults in central Virginia recruited without regard to the history of allergic disease. METHODS: Adults in central Virginia, primarily University of Virginia Health employees, were recruited as part of a COVID-19 vaccine study. Subjects provided at least one blood sample and answered questionnaires about medical and dietary history. We used ImmunoCAP for IgE assays and assessed the ABO blood group by reverse typing using stored serum. We also investigated biobanked serum from COVID-19 patients. RESULTS: Median age of the 267 enrollees was 42 years, 76% were female, and 43 (16%) were sensitized to alpha-gal (cutoff of 0.1 IU/mL), of which mammalian meat allergy was reported by seven (2.6%). Sensitized subjects (1) were older, (2) had higher total IgE levels but a similar frequency of IgE to common respiratory allergens, and (3) were more likely to report tick bites than were nonsensitized subjects. Among those who were sensitized, alpha-gal IgE levels were higher among meat-allergic than nonallergic subjects (geometric mean, 9.0 vs 0.5 IU/mL; P < .001). Mammalian meat and dairy consumption was common in individuals with low-level sensitization. CONCLUSION: In central Virginia, AGS is a dominant cause of adult food allergy with a prevalence approaching or exceeding 2%.
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COVID-19 , Hipersensibilidade Alimentar , Imunoglobulina E , Humanos , Imunoglobulina E/sangue , Feminino , Masculino , Adulto , Virginia/epidemiologia , Pessoa de Meia-Idade , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/diagnóstico , COVID-19/imunologia , COVID-19/epidemiologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2/imunologia , Estudos de Coortes , Picadas de Carrapatos/imunologia , Picadas de Carrapatos/epidemiologia , Prevalência , Fatores de Risco , Alérgenos/imunologia , Animais , Carne , Idoso , Dissacarídeos/imunologiaRESUMO
STUDY DESIGN: This was a retrospective case-control study using 8 years of data from a nationwide database of surgical outcomes in the United States. PURPOSE: This study aimed to improve our understanding of the risk factors associated with a length of stay (LOS) >1 day and aid in reducing postoperative hospitalization and complications. OVERVIEW OF LITERATURE: Despite the proven safety of transforaminal lumbar interbody fusion (TLIF), some patients face prolonged postoperative hospitalization. METHODS: Data were collected from the American College of Surgeons National Surgical Quality Improvement Program dataset from 2011 to 2018. The cohort was divided into patients with LOS up to 1 day (LOS ≤1 day), defined as same day or next-morning discharge, and patients with LOS >1 day (LOS >1 day). Univariable and multivariable regression analyses were performed to evaluate predictors of LOS >1 day. Propensity-score matching was performed to compare pre- and postdischarge complication rates. RESULTS: A total of 12,664 eligible patients with TLIF were identified, of which 14.8% had LOS ≤1 day and 85.2% had LOS >1 day. LOS >1 day was positively associated with female sex, Hispanic ethnicity, diagnosis of spondylolisthesis, American Society of Anesthesiologists classification 3, and operation length of >150 minutes. Patients with LOS >1 day were more likely to undergo intraoperative/postoperative blood transfusion (0.3% vs. 4.5%, p<0.001) and reoperation (0.1% vs. 0.6%, p=0.004). No significant differences in the rates of postdischarge complications were found between the matched groups. CONCLUSIONS: Patients with worsened preoperative status, preoperative diagnosis of spondylolisthesis, and prolonged operative time are more likely to require prolonged hospitalization and blood transfusions and undergo unplanned reoperation. To reduce the risk of prolonged hospitalization and associated complications, patients indicated for TLIF should be carefully selected.
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Childhood cancer survivorship studies generate comprehensive datasets comprising demographic, diagnosis, treatment, outcome, and genomic data from survivors. To broadly share this data, we created the St. Jude Survivorship Portal (https://survivorship.stjude.cloud), the first data portal for sharing, analyzing, and visualizing pediatric cancer survivorship data. More than 1,600 phenotypic variables and 400 million genetic variants from more than 7,700 childhood cancer survivors can be explored on this free, open-access portal. Summary statistics of variables are computed on-the-fly and visualized through interactive and customizable charts. Survivor cohorts can be customized and/or divided into groups for comparative analysis. Users can also seamlessly perform cumulative incidence and regression analyses on the stored survivorship data. Using the portal, we explored the ototoxic effects of platinum-based chemotherapy, uncovered a novel association between mental health, age, and limb amputation, and discovered a novel haplotype in MAGI3 strongly associated with cardiomyopathy specifically in survivors of African ancestry. Significance: The St. Jude Survivorship Portal is the first data portal designed to share and explore clinical and genetic data from childhood cancer survivors. The portal provides both open- and controlled-access features and will fulfill a wide range of data sharing needs of the survivorship research community and beyond. See co-corresponding author Xin Zhou discuss this research article, published simultaneously at the AACR Annual Meeting 2024: https://vimeo.com/932617204/7d99fa4958.
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Sobreviventes de Câncer , Genômica , Neoplasias , Humanos , Criança , Genômica/métodos , Neoplasias/genética , Disseminação de Informação , Masculino , Feminino , Adolescente , SobrevivênciaRESUMO
Parkinson's disease (PD) is a progressive neurodegenerative condition that pathognomonically involves the death of dopaminergic neurons in the substantia nigra pars compacta, resulting in a myriad of motor and non-motor symptoms. Given the insurmountable burden of this disease on the population and healthcare system, significant efforts have been put forth toward generating disease modifying therapies. This class of treatments characteristically alters disease course, as opposed to current strategies that focus on managing symptoms. Previous literature has implicated the cell death pathway known as parthanatos in PD progression. Inhibition of this pathway by targeting poly (ADP)-ribose polymerase 1 (PARP1) prevents neurodegeneration in a model of idiopathic PD. However, PARP1 has a vast repertoire of functions within the body, increasing the probability of side effects with the long-term treatment likely necessary for clinically significant neuroprotection. Recent work culminated in the development of a novel agent targeting the macrophage migration inhibitory factor (MIF) nuclease domain, also named parthanatos-associated apoptosis-inducing factor nuclease (PAAN). This nuclease activity specifically executes the terminal step in parthanatos. Parthanatos-associated apoptosis-inducing factor nuclease inhibitor-1 was neuroprotective in multiple preclinical mouse models of PD. This piece will focus on contextualizing this discovery, emphasizing its significance, and discussing its potential implications for parthanatos-directed treatment. © 2024 International Parkinson and Movement Disorder Society.
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Neurônios Dopaminérgicos , Fatores Inibidores da Migração de Macrófagos , Doença de Parkinson , Humanos , Neurônios Dopaminérgicos/metabolismo , Doença de Parkinson/metabolismo , Animais , Fatores Inibidores da Migração de Macrófagos/metabolismo , Fatores Inibidores da Migração de Macrófagos/antagonistas & inibidores , Poli(ADP-Ribose) Polimerase-1/metabolismo , Parthanatos/efeitos dos fármacosRESUMO
BACKGROUND: The concept of sleep bruxism (SB) has evolved exponentially over the past several decades. Many theories and hypotheses have been proposed as to the definition, pathophysiology, and management of SB, from the early 1960s through the present. The role of peripheral factors, such as dental occlusion, in the pathogenesis of SB has been discarded. TYPES OF STUDIES REVIEWED: The authors searched several electronic databases (ie, PubMed, Google Scholar, Web of Science, Embase, and Ovid MEDLINE) for studies on bruxism. The search was conducted from January 1961 through May 2023 and yielded 4,612 articles, of which 312 were selected for comprehensive review after eliminating duplicates and nonfocused articles. RESULTS: There has been an evident progressive shift from the role of peripheral factors, such as dental occlusion, to more central factors, such as the involvement of a central pattern generator as well as the autonomic nervous system, in the genesis of bruxing movements. There is continued robust interest in the dental community to elucidate the contributing factors involved in SB. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The neurophysiology of SB appears to be leaning more toward central rather than peripheral factors. There is increasing evidence of the role of the autonomic nervous system, genetics, and comorbidities in the genesis of SB. The scientific literature seems to refute the role of dental occlusion in the causation of bruxing movements. As per the literature, there has been a paradigm shift in the definition and genesis of SB and its possible dental implications and management, which also highlights the need for succinct scientific studies in this regard.
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Bruxismo do Sono , Humanos , Bruxismo do Sono/diagnóstico , Bruxismo do Sono/terapia , Polissonografia/efeitos adversosRESUMO
Neuroblastoma is a pediatric cancer arising from the developing sympathoadrenal lineage with complex inter- and intra-tumoral heterogeneity. To chart this complexity, we generated a comprehensive cell atlas of 55 neuroblastoma patient tumors, collected from two pediatric cancer institutions, spanning a range of clinical, genetic, and histologic features. Our atlas combines single-cell/nucleus RNA-seq (sc/scRNA-seq), bulk RNA-seq, whole exome sequencing, DNA methylation profiling, spatial transcriptomics, and two spatial proteomic methods. Sc/snRNA-seq revealed three malignant cell states with features of sympathoadrenal lineage development. All of the neuroblastomas had malignant cells that resembled sympathoblasts and the more differentiated adrenergic cells. A subset of tumors had malignant cells in a mesenchymal cell state with molecular features of Schwann cell precursors. DNA methylation profiles defined four groupings of patients, which differ in the degree of malignant cell heterogeneity and clinical outcomes. Using spatial proteomics, we found that neuroblastomas are spatially compartmentalized, with malignant tumor cells sequestered away from immune cells. Finally, we identify spatially restricted signaling patterns in immune cells from spatial transcriptomics. To facilitate the visualization and analysis of our atlas as a resource for further research in neuroblastoma, single cell, and spatial-omics, all data are shared through the Human Tumor Atlas Network Data Commons at www.humantumoratlas.org.
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BACKGROUND: IgE to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal) is an important cause of allergic reactions to mammalian meat. The "alpha-gal syndrome" is strongly associated with a preceding history of tick bites and in the United States is most commonly reported in parts of the southeast, but there has been limited investigation into national alpha-gal sensitization patterns and the relevance of other risk factors. OBJECTIVE: To systematically investigate alpha-gal IgE prevalence, regional patterns, and risk factors. METHODS: Alpha-gal IgE was measured by ImmunoCAP in biobanked serum samples collected from 3000 service members who presented for intake to 1 of 10 military bases in the central/eastern United States. Alpha-gal IgE sensitization (cutoff 0.1 international units/mL) was related to home of record at enlistment. RESULTS: Of the cohort, 2456 (81.9%) subjects were male, median age was 19 years (interquartile range: 18-22 years), and alpha-gal IgE was detected in 179 (6.0%). Home of record spanned all 50 states, with a median of 36 recruits per state (range: 3-261). The highest prevalence rates were in Arkansas (39%), Oklahoma (35%), and Missouri (29%), with several other southeastern states >10%. Granular mapping revealed sensitization patterns that closely mimicked county-level Amblyomma americanum reports and Ehrlichia chaffeensis infections. Sensitization was associated with male sex, rural residence, and White race in univariate and multivariable models. CONCLUSIONS: In this systematic survey, the prevalence of alpha-gal IgE among incoming military personnel was 6.0%. There were significant regional differences, with an overall pattern consistent with the known range of the lone star tick (A. americanum) and highest frequency in an area including Arkansas, Oklahoma, and Missouri.
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Hipersensibilidade Alimentar , Militares , Animais , Feminino , Humanos , Masculino , Adulto Jovem , Alérgenos , Galactose , Imunoglobulina E , Mamíferos , Prevalência , Estados Unidos/epidemiologiaRESUMO
Lymphangioleiomyomatosis (LAM) is a rare, slow-growing metastasizing neoplasm in which smooth muscle-like cells infiltrate the lung parenchyma and cause cystic lung damage. The common early symptoms include shortness of breath, pneumothorax, and chest pain. Lymphangioleiomyomatosis mainly involves the lungs, kidneys, and lymph nodes. This study reviews the characteristics of lymphangioleiomyomatosis to identify any possible changes in the prevalence of symptoms of the disease. We conducted a literature review of case reports on lymphangioleiomyomatosis from PubMed and Google Scholar. Variables of interest were age, gender, symptoms, vitals, immunostaining, and radiological findings. Data were transferred to an Excel spreadsheet (Microsoft Corporation, Redmond, WA), and mean, median, standard deviation, frequencies, and proportions were calculated using R version 1.1.456 (RStudio: Integrated Development for R. RStudio, PBC, Boston, MA). Lymphangioleiomyomatosis is a rare case and so not much of the literature could be found online. Thirty-three case reports were included in this study, and females accounted for 78.78% of the presentations. The average age was 38 years, SD 14.41 years. Shortness of breath was the most frequent symptom (60.6%), followed by pneumothorax (57.57%), chest pain (42.42%), cough (24.24%), and pleural effusion (1.25%).
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Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer's and Parkinson's disease. It has also been beneficial against noise-induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.
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NAD , Presbiacusia , Humanos , Animais , Camundongos , Receptores Ativados por Proliferador de Peroxissomo , Presbiacusia/tratamento farmacológico , Presbiacusia/prevenção & controle , Cóclea , Suplementos NutricionaisRESUMO
Infective endocarditis (IE) can present with a wide variety of clinical signs and symptoms, making it difficult to diagnose. Recognizing risk factors such as congenital heart disease, intravenous drug use, and prosthetic heart valves can encourage early testing with blood cultures and echocardiography, leading to prompt diagnosis and treatment with antibiotics. Despite early detection and treatment, IE can still result in permanent damage of the affected heart valves, most commonly resulting in valvular regurgitation and signs and symptoms of heart failure. Clinicians must maintain a high index of suspicion as prompt diagnosis and treatment are essential to prevent morbidity and mortality. Valvular stenosis as a result of IE, unlike valvular regurgitation, is extremely rare and has only been described a handful of times in literature. We present a unique case of Streptococcus viridans IE resulting in functional mitral stenosis and recurrent flash pulmonary edema in an elderly female who had recently undergone a dental cleaning procedure.
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Acute respiratory distress syndrome (ARDS) is a highly heterogeneous clinical condition. Shock is a poor prognostic sign in ARDS, and heterogeneity in its pathophysiology may be a barrier to its effective treatment. Although right ventricular dysfunction is commonly implicated, there is no consensus definition for its diagnosis, and left ventricular function is neglected. There is a need to identify the homogenous subgroups within ARDS, that have a similar pathobiology, which can then be treated with targeted therapies. Haemodynamic clustering analyses in patients with ARDS have identified two subphenotypes of increasingly severe right ventricular injury, and a further subphenotype of hyperdynamic left ventricular function. In this review, we discuss how phenotyping the cardiovascular system in ARDS may align with haemodynamic pathophysiology, can aid in optimally defining right ventricular dysfunction and can identify tailored therapeutic targets for shock in ARDS. Additionally, clustering analyses of inflammatory, clinical and radiographic data describe other subphenotypes in ARDS. We detail the potential overlap between these and the cardiovascular phenotypes.
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SUMMARY: ProteinPaint BAM track (ppBAM) is designed to assist variant review for cancer research and clinical genomics. With performant server-side computing and rendering, ppBAM supports on-the-fly variant genotyping of thousands of reads using Smith-Waterman alignment. To better visualize support for complex variants, reads are realigned against the mutated reference sequence using ClustalO. ppBAM also supports the BAM slicing API of the NCI Genomic Data Commons (GDC) portal, letting researchers conveniently examine genomic details of vast amounts of cancer sequencing data and reinterpret variant calls. AVAILABILITY AND IMPLEMENTATION: BAM track examples, tutorial, and GDC file access links are available at https://proteinpaint.stjude.org/bam/. Source code is available at https://github.com/stjude/proteinpaint.
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Genômica , Software , Análise de Sequência de DNA , Genótipo , Alinhamento de Sequência , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
OBJECTIVE: The two main objectives of this study were to explore the rate of spinal dysraphism within bladder and cloacal exstrophy and to analyze the relationship between spinal dysraphism surgery, including timing of spinal dysraphism surgery, with urological and neurological outcomes. METHODS: A prospectively maintained IRB-approved database of pediatric exstrophy patients treated from 1982 to 2021 was retrospectively reviewed for patients with spinal dysraphism. Spinal dysraphism was categorized into the following 7 subtypes: lipoma-based closed defect, myelomeningocele, meningocele, diastematomyelia, myelocystocele, low-lying conus with tethered cord/fatty filum, and sacral bony defect. Other factors assessed included patient demographic characteristics, type of spinal dysraphism procedure, reoperation, complication, presence of other neurological problems (e.g., hydrocephalus, Chiari malformation), neurological status, and urological function. RESULTS: Analysis revealed that 114/1401 patients had coexisting spinal dysraphism. Of these 114, sufficient records including type of dysraphism were available for 54. Spinal dysraphism was most common within cloacal exstrophy (83.3% [45/54 patients]), followed by cloacal exstrophy variants (9.3% [5/54]), classic bladder exstrophy (3.7% [2/54]), and classic bladder exstrophy variants (3.7% [2/54]). Within spinal dysraphism, lipoma-based closed defects (63.0% [34/54]) and low-lying conus with tethered cord/fatty filum (11.1% [6/54]) were most common. Hydrocephalus and Chiari malformation occurred in 24.1% (13/54) and 11.1% (6/54) of patients. All 13 patients with hydrocephalus underwent shunt placement. Among those who underwent neurosurgical intervention, the complication rate for spinal dysraphism was 14.6% (7/48). Motor function data were available for 41 patients and revealed that motor function declined for 2/41 (4.8%) patients and improved for 6/41 (14.6%) after neurosurgery. There was no statistical difference in lower-extremity motor outcome related to timing of neurosurgery and exstrophy closure. CONCLUSIONS: The authors have reported the surgical management and outcomes of patients with exstrophy and coexisting spinal dysraphism (n = 54). In 54 patients, spinal dysraphism was most common in the subset of patients with cloacal exstrophy (83.3%). Lipoma-based closed defects (63.0%) and low-lying conus with tethered cord/fatty filum (11.1%) were the most common, and the rates of hydrocephalus and Chiari malformation were 24.1% and 11.1%, respectively. There was no difference in lower-extremity motor outcome related to timing of neurosurgery and exstrophy closure.
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Malformação de Arnold-Chiari , Extrofia Vesical , Anormalidades do Sistema Digestório , Hidrocefalia , Lipoma , Meningomielocele , Defeitos do Tubo Neural , Disrafismo Espinal , Humanos , Criança , Extrofia Vesical/complicações , Extrofia Vesical/epidemiologia , Extrofia Vesical/cirurgia , Estudos Retrospectivos , Disrafismo Espinal/complicações , Disrafismo Espinal/epidemiologia , Disrafismo Espinal/cirurgia , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/cirurgia , Meningomielocele/cirurgia , Malformação de Arnold-Chiari/cirurgia , Hidrocefalia/cirurgia , Lipoma/complicações , Lipoma/epidemiologia , Lipoma/cirurgiaRESUMO
Background: The use of cannabis has massively increased among younger patients due to increasing legalization and availability. Methods: We performed a retrospective nationwide study using the Nationwide inpatient sample (NIS) database to analyze the trends of acute myocardial infarction (AMI) in young cannabis users and related outcomes among patients aged 18-49 years from 2007 to 2018, using ICD-9 and ICD-10 codes. Results: Out of 819,175 hospitalizations, 230,497 (28%) admissions reported using cannabis. There was a significantly higher number of males (78.08% vs. 71.58%, p < 0.0001) and African Americans (32.22% vs. 14.06%, p < 0.0001) admitted with AMI and reported cannabis use. The incidence of AMI among cannabis users consistently increased from 2.36% in 2007 to 6.55% in 2018. Similarly, the risk of AMI in cannabis users among all races increased, with the biggest increase in African Americans from 5.69% to 12.25%. In addition, the rate of AMI in cannabis users among both sexes showed an upward trend, from 2.63% to 7.17% in males and 1.62%-5.12% in females. Conclusion: The incidence of AMI in young cannabis users has increased in recent years. The risk is higher among males and African Americans.
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OBJECTIVES: To use clustering methods on transthoracic echocardiography (TTE) findings and hemodynamic parameters to characterize circulatory failure subphenotypes and potentially elucidate underlying mechanisms in patients with acute respiratory distress syndrome (ARDS) and to describe their association with mortality compared with current definitions of right ventricular dysfunction (RVD). DESIGN: Retrospective, single-center cohort study. SETTING: University Hospital ICU, Birmingham, United Kingdom. PATIENTS: ICU patients that received TTE within 7 days of ARDS onset between April 2016 and December 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Latent class analysis (LCA) of TTE/hemodynamic parameters was performed in 801 patients, 62 years old (interquartile range, 50-72 yr old), 63% male, and 40% 90-day mortality rate. Four cardiovascular subphenotypes were identified: class 1 (43%; mostly normal left and right ventricular [LV/RV] function), class 2 (24%; mostly dilated RV with preserved systolic function), class 3 (13%, mostly dilated RV with impaired systolic function), and class 4 (21%; mostly high cardiac output, with hyperdynamic LV function). The four subphenotypes differed in their characteristics and outcomes, with 90-day mortality rates of 19%, 40%, 78%, and 59% in classes 1-4, respectively ( p < 0.0001). Following multivariable logistic regression analysis, class 3 had the highest odds ratio (OR) for mortality (OR, 6.9; 95% CI, 4.0-11.8) compared with other RVD definitions. Different three-variable models had high diagnostic accuracy in identifying each of these latent subphenotypes. CONCLUSIONS: LCA of TTE parameters identified four cardiovascular subphenotypes in ARDS that more closely aligned with circulatory failure mechanisms and mortality than current RVD definitions.
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Síndrome do Desconforto Respiratório , Disfunção Ventricular Direita , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos de Coortes , Estudos Retrospectivos , Ecocardiografia/métodos , Ventrículos do Coração , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/complicaçõesRESUMO
Mucoceles are benign lesions of salivary glands typically originating from the paranasal sinuses. Intracranial extension and superinfection of these lesions are rare but serious complications of chronic mucoceles. Here, we discuss a patient with a known mucocele, initially lost to follow-up, who presented three years later with headache, purulent rhinorrhea, and intracranial extension of his mucocele with development of an epidural abscess. This case highlights the potential complications of chronic, large mucoceles and emphasizes the importance of thorough evaluation in patients with facial abscesses in the setting of known sinus pathology. Any mucocele with signs of superinfection such as purulent rhinorrhea, abscess near the sinuses, or refractory symptoms should warrant cranial imaging. Mucoceles with evidence of intracranial extension require neurosurgical and/or otolaryngologic evaluation for evacuation and debridement to avoid neurologic injury or devastating infection.
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Parkinson's disease is the second most prevalent neurodegenerative disease and contributes significantly to morbidity globally. Currently, no disease-modifying therapies exist to combat this disorder. Insights from the molecular and cellular pathobiology of the disease seems to indicate promising therapeutic targets. The parkin protein has been extensively studied for its role in autosomal recessive Parkinson's disease and, more recently, its role in sporadic Parkinson's disease. Parkin is an E3 ubiquitin ligase that plays a prominent role in mitochondrial quality control, mitochondrial-dependent cell death pathways, and other diverse functions. Understanding the numerous roles of parkin has introduced many new possibilities for therapeutic modalities in treating both autosomal recessive Parkinson's disease and sporadic Parkinson's disease. In this article, we review parkin biology with an emphasis on mitochondrial-related functions and propose novel, potentially disease-modifying therapeutic approaches for treating this debilitating condition.