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1.
Cardiol Young ; : 1-6, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38410052

RESUMO

OBJECTIVE: To describe a method of reducing the risk of sternal wound infection after sternotomy in children with a pre-existing tracheostomy. To report our outcomes using this method from 1 January, 2013 to 31 August, 2023. METHODS: We describe a method for temporarily occluding the tracheal stoma with a removable implant with the primary goal of reducing the risk of sternotomy wound infection by preventing soilage due to tracheostomal secretions. We then performed a retrospective review of all children who underwent temporary tracheostomal occlusion between 1 January, 2013 and 31 August, 2023 at our quaternary care children's hospital. Clinical variables were extracted from the hospital medical records. The rates of antibiotic use and minor and major complications during the period when the stoma plug was in place were recorded. RESULTS: Totally, 19 patients underwent tracheal stoma plugging prior to sternotomy and were included in our analysis. There were two cases of sternal wound infection; one case occurred while the stoma plug was in place, and one developed four days following plug removal. There was one minor complication, with one patient requiring stoma revision via serial dilation at bedside at the time of recannulation. There were no deaths. CONCLUSION: Temporary occlusion of the tracheal stoma with an impermeable plug is a viable option for reducing the risk of sternal wound infection in children with a pre-existing tracheostomy who are undergoing sternotomy.

2.
Otolaryngol Head Neck Surg ; 170(1): 151-158, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37435656

RESUMO

OBJECTIVE: The value-based healthcare model aims to improve the quality of care and lower health care costs. The standard value equation (ie, Value = Quality/Cost), while conceptually useful, is grossly oversimplified and lacks clinical relevance. This study introduces a more detailed value equation that generates disease-specific value scores and incorporates real-world clinical and cost data to demonstrate its use. STUDY DESIGN: Prospective observational study. SETTING: Tertiary institution. METHODS: A comprehensive new health care value equation was developed that includes 23 unique inputs. Sixteen inputs represent quality (numerator) and 7 inputs represent cost (denominator). Patients undergoing thyroid or parathyroid surgery were enrolled, and data were entered into the new equation to generate surgery-specific value scores for each patient. A subanalysis was performed for telehealth visits. RESULTS: Ten patients were enrolled (60% female) with an average age of 62 years. The average total monetary cost per patient was $41,884 ($27,885 direct). Across all patients, the average total quality score was 0.99, and the cost score was 6.1, resulting in a final value score of 0.19. A subanalysis showed that changing a postoperative visit from in-person to telehealth would increase the value score by 0.66%. CONCLUSION: This analysis creates a comprehensive value equation for surgical services that incorporates the complexity of modern surgical care. The new equation includes objective and subjective outcomes and health equity, quantitatively compares the value of different surgical interventions and health care services, illustrates how specific interventions can lead to the higher value of care, and can serve as the framework for future value equations.


Assuntos
Procedimentos Cirúrgicos Endócrinos , Pacientes Ambulatoriais , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Custos de Cuidados de Saúde , Atenção à Saúde , Estudos Prospectivos
3.
Curr Otorhinolaryngol Rep ; 11(3): 201-214, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38073717

RESUMO

Purpose of review: To summarize the current literature on allyship, providing a historical perspective, concept analysis, and practical steps to advance equity, diversity, and inclusion. This review also provides evidence-based tools to foster allyship and identifies potential pitfalls. Recent findings: Allies in healthcare advocate for inclusive and equitable practices that benefit patients, coworkers, and learners. Allyship requires working in solidarity with individuals from underrepresented or historically marginalized groups to promote a sense of belonging and opportunity. New technologies present possibilities and perils in paving the pathway to diversity. Summary: Unlocking the power of allyship requires that allies confront unconscious biases, engage in self-reflection, and act as effective partners. Using an allyship toolbox, allies can foster psychological safety in personal and professional spaces while avoiding missteps. Allyship incorporates goals, metrics, and transparent data reporting to promote accountability and to sustain improvements. Implementing these allyship strategies in solidarity holds promise for increasing diversity and inclusion in the specialty.

5.
Int J Pediatr Otorhinolaryngol ; 172: 111631, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37567085

RESUMO

INTRODUCTION: Comorbidities such as chronic lung disease and gastroesophageal reflux (GERD), prematurity, and numerous other conditions may impact the success of LTR. Single-center studies are limited in terms of patient numbers and may be underpowered. OBJECTIVES: To analyze the impact of specific comorbidities on the operation-specific and overall surgical success of LTR in a large multicenter cohort and validate a predictive model for surgical success. METHODS: A large retrospective multicenter 10-year review was undertaken to validate the data of a previous single-center study (Wertz et al. Laryngoscope 2020) which identified specific predictive comorbidities which impacted LTR outcomes. A Monte Carlo simulation based on the previous data set suggested that 300-400 cases would be needed to optimize the statistical power of a Bayesian model developed from the single-center data to predict surgical success. An IRB-approved data-sharing agreement was executed for 4 large U.S. CENTERS: A virtual REDCap® data entry form inquired about patient characteristics that best predicted surgical success in the single-center model. These included demographics, surgical approaches, cardiac, airway, genetic, endocrine, musculoskeletal, gastrointestinal, and pulmonary comorbidities; details of the surgical procedures, and results of esophagogastroduodenoscopy (EGD), esophageal pH/impedance and flexible bronchoscopy with bronchioalveolar lavage (BAL) were included. Surgical success defined as successful decannulation or resolution of airway symptoms was recorded as single surgery success and overall success following open surgical revision surgery. Multivariate Bayesian analysis, logistical regression, and Kaplan-Meier analysis were performed. RESULTS: 542 patients were identified, including 165 from the single-center study and an additional 377 patients from the multicenter group. The median age was 36 months at the time of the most recent surgery. 70.9% of the LTRs were double-staged procedures. The overall success rate was 86.4% and operation-specific success rate was 69.2%. The specific comorbidities and aerodigestive test results that impacted success based on univariate analysis included staging, bronchiectasis, pulmonary hypertension, GERD, ASD, PDA, grade of stenosis, advanced levels of stenosis, Trisomy 21, MRSA, prior open surgery at another hospital, and gross appearance on EGD. Bayesian model averaging with backward selection was used to validate and refine a predictive model for surgical success with favorable receiver operating curve characteristics - AUC values of 0.827 for single surgery success and 0.797 for overall success. DISCUSSION: With over 500 patients reviewed, this was the largest multicenter study of LTR to date, which elucidated the impact of comorbidities on success with LTR and was able to improve upon the predictive modeling based on single-center data. Patient factors are most critical in the outcome of LTR. Stage and levels of stenosis, as well as pulmonary and GI conditions most strongly impact the likelihood of success. Future prospective case-control studies will be performed to further optimize the current model for outcome prediction and patient management.


Assuntos
Refluxo Gastroesofágico , Laringoestenose , Estenose Traqueal , Humanos , Pré-Escolar , Laringoestenose/complicações , Laringoestenose/epidemiologia , Laringoestenose/cirurgia , Estenose Traqueal/complicações , Estenose Traqueal/epidemiologia , Estenose Traqueal/cirurgia , Constrição Patológica , Teorema de Bayes , Estudos Retrospectivos , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/epidemiologia , Resultado do Tratamento
6.
Otolaryngol Head Neck Surg ; 169(4): 830-836, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37157972

RESUMO

OBJECTIVE: Radiofrequency ablation (RFA) of benign thyroid nodules has gained traction for its therapeutic effectiveness, thyroid function preservation, and minimally invasive nature. While a growing body of evidence reports positive outcomes from thyroid RFA, financial comparisons between both procedures remain limited. This analysis aims to more accurately measure the direct cost of thyroid RFA in comparison to thyroid lobectomy. STUDY DESIGN: Bottom-up financial cost analysis. SETTING: Tertiary endocrine head and neck surgery center. METHODS: Time-driven activity-based costing was utilized to obtain unit-based cost estimates. The care cycles for thyroid lobectomy and RFA were defined, and process maps were developed comprising all personnel and work in the care cycle. Time estimates were calculated for all personnel involved, and public government data were used to obtain capacity cost rates for each component of the care cycle. Consumable supply and overhead costs were obtained for both procedures, and overall costs were compared. RESULTS: For thyroid lobectomy, total personnel costs were $1087.97, consumable supplies were $942.68, and overhead costs $17,199.10. For thyroid nodule RFA performed in an office setting, the total personnel cost calculated was $379.90, consumable supplies $1315.28, and overhead $7031.20. Overall, the total cost for thyroid lobectomy was $19,229.75 compared to $8726.38 for RFA. CONCLUSION: In-office thyroid nodule RFA is associated with lower direct costs than thyroid lobectomy, and overhead is the greatest cost driver for both procedures. If clinical and patient-centered outcomes are comparable, then RFA may provide higher value for appropriately selected patients.


Assuntos
Ablação por Cateter , Ablação por Radiofrequência , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/cirurgia , Ablação por Cateter/métodos , Resultado do Tratamento , Estudos Retrospectivos , Ablação por Radiofrequência/métodos , Custos e Análise de Custo
7.
Laryngoscope ; 133(12): 3588-3601, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37114735

RESUMO

OBJECTIVE: To achieve consensus on critical steps and create an assessment tool for actual and simulated pediatric tracheostomy emergencies that incorporates human and systems factors along with tracheostomy-specific steps. METHODS: A modified Delphi method was used. Using REDCap software, an instrument comprising 29 potential items was circulated to 171 tracheostomy and simulation experts. Consensus criteria were determined a priori with a goal of consolidating and ordering 15 to 25 final items. In the first round, items were rated as "keep" or "remove". In the second and third rounds, experts were asked to rate the importance of each item on a 9-point Likert scale. Items were refined in subsequent iterations based on analysis of results and respondents' comments. RESULTS: The response rates were 125/171 (73.1%) for the first round, 111/125 (88.8%) for the second round, and 109/125 (87.2%) for the third round. 133 comments were incorporated. Consensus (>60% participants scoring ≥8, or mean score >7.5) was reached on 22 items distributed across three domains. There were 12, 4, and 6 items in the domains of tracheostomy-specific steps, team and personnel factors, and equipment respectively. CONCLUSIONS: The resultant assessment tool can be used to assess both tracheostomy-specific steps as well as systems factors affecting hospital team response to simulated and clinical pediatric tracheostomy emergencies. The tool can also be used to guide debriefing discussions of both simulated and clinical emergencies, and to spur quality improvement initiatives. LEVEL OF EVIDENCE: 5 Laryngoscope, 133:3588-3601, 2023.


Assuntos
Emergências , Traqueostomia , Humanos , Criança , Consenso , Técnica Delfos , Simulação por Computador
8.
JAMA Otolaryngol Head Neck Surg ; 149(6): 556-558, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37103921

RESUMO

This qualitative study rates the level of understandability, actionability, and procedure-specific content in postoperative instructions generated from ChatGPT, Google Search, and Stanford University.


Assuntos
Letramento em Saúde , Ferramenta de Busca , Humanos
9.
Int J Pediatr Otorhinolaryngol ; 168: 111542, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37058865

RESUMO

INTRODUCTION: Injection laryngoplasty (IL) is commonly performed for unilateral vocal fold immobility (UVFI). However, the safety and efficacy in patients <1 year of age are not widely recognized. This study analyzes the safety and swallow outcomes in a cohort of patients <1 year who underwent IL. METHODS: This retrospective analysis evaluated patients at a tertiary children's institution between 2015 and 2022. Patients were eligible if they underwent IL for UVFI and were <1 year at time of injection. Baseline characteristics, perioperative data, oral diet tolerance, and preoperative and postoperative swallow data were collected. RESULTS: 49 patients were included, 12 (24%) of whom were premature. The average age at injection was 3.9 months (SD 3.8), time from UVFI onset to injection 1.3 months (2.0), and weight at injection 4.8 kg (2.1). The baseline American Association of Anesthesiologists physical status classification scores were 2 (14%), 3 (61%), and 4 (24%). 89% of patients had improvements in objective swallow function postoperatively. Of the 35 patients who were preoperatively enterally-dependent and did not have medical circumstances precluding advancement to oral feeds, 32 (n = 91%) tolerated an oral diet postoperatively. There were no long-term sequelae. Two patients had intraoperative laryngospasm, one intraoperative bronchospasm, and one with subglottic and posterior glottic stenosis was intubated for <12 h for increased work of breathing. CONCLUSIONS: IL is a safe and effective intervention that can reduce aspiration and improve diet in patients <1 year old. This procedure can be considered at institutions with the appropriate personnel, resources, and infrastructure.


Assuntos
Laringoplastia , Paralisia das Pregas Vocais , Criança , Humanos , Lactente , Laringoplastia/métodos , Prega Vocal/cirurgia , Paralisia das Pregas Vocais/cirurgia , Paralisia das Pregas Vocais/complicações , Estudos Retrospectivos , Resultado do Tratamento
10.
Otolaryngol Head Neck Surg ; 169(4): 1020-1027, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36994937

RESUMO

OBJECTIVE: The past 2 decades have seen a rapid increase in the diagnosis of ankyloglossia. Patients are often managed by lingual frenotomy. The objective is to define the clinical and socioeconomic factors that determine which patients receive frenotomy. STUDY DESIGN: A retrospective analysis of commercially insured children. SETTING: Optum Data Mart database. METHODS: Trends in frenotomy including provider and setting were described. Multiple logistic regression was used to determine predictors of frenotomy. RESULTS: Diagnosis of ankyloglossia increased from 2004 to 2019 (from 3377 in 2004 to 13,200 in 2019), while lingual frenotomy similarly increased from 1483 in 2004 to 6213 in 2019. The proportion of inpatient frenotomy procedures increased from 6.2% to 16.6% from 2004 to 2019, with pediatricians having the highest odds of performing inpatient frenotomies (odds ratio: 4.32, 95% confidence interval: 4.08, 4.57). Additionally, during the study period, the proportion of frenotomies performed by pediatricians increased from 13.01% in 2004 to 28.38% in 2019. In multivariate regression analyses, frenotomy was significantly associated with the male sex, white non-Hispanic ethnicity, higher parental income and education, and a greater number of siblings. CONCLUSION: Ankyloglossia has been increasingly diagnosed in the past 2 decades, and among patients with ankyloglossia, frenotomy is increasingly performed. This trend was driven at least in part due to increasing rates of pediatricians as proceduralists. After accounting for maternal and patient-level clinical factors, socioeconomic differences in the management of ankyloglossia were observed.


Assuntos
Anquiloglossia , Criança , Humanos , Masculino , Estados Unidos , Lactente , Anquiloglossia/diagnóstico , Anquiloglossia/cirurgia , Estudos Retrospectivos , Freio Lingual/cirurgia , Pacientes Internados , Pais
11.
Int J Pediatr Otorhinolaryngol ; 166: 111469, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36764081

RESUMO

INTRODUCTION: Non-tuberculous mycobacterial (NTM) infection commonly manifests as subacute or chronic cervicofacial lymphadenitis in immunocompetent children. The optimal management of this pathology remains controversial. OBJECTIVES: This international consensus guideline aims to understand the practice patterns for NTM cervicofacial lymphadenitis and to address the primary diagnostic and management challenges. METHODS: A modified three-iterative Delphi method was used to establish expert recommendations on the diagnostic considerations, expectant or medical management, and operative considerations. The recommendations herein are derived from current expert consensus and critical review of the literature. SETTING: Multinational, multi-institutional, tertiary pediatric hospitals. RESULTS: Consensus recommendations include diagnostic work-up, goals of treatment and management options including surgery, prolonged antibiotic therapy and observation. CONCLUSION: The recommendations formulated in this International Pediatric Otolaryngology Group (IPOG) consensus statement on the diagnosis and management of patients with NTM lymphadenitis are aimed at improving patient care and promoting future hypothesis generation.


Assuntos
Linfadenite , Infecções por Mycobacterium não Tuberculosas , Otolaringologia , Criança , Humanos , Micobactérias não Tuberculosas , Linfadenite/microbiologia , Antibacterianos/uso terapêutico , Excisão de Linfonodo , Infecções por Mycobacterium não Tuberculosas/diagnóstico
12.
Cleft Palate Craniofac J ; 60(6): 758-767, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35167404

RESUMO

We recently published the 3-month follow-up of 2 neonates with Robin sequence whose mandibular hypoplasia and restricted airway were successfully treated with an orthodontic airway plate (OAP) without surgical intervention. Both infants were successfully weaned off the OAP after several months of continuous use. We present the course of OAP treatment in these patients with a focus on breathing, feeding, and facial growth during their first year of life. Both infants demonstrated stable mandibular projection, resolution of obstructive sleep apnea, and normal development.


Assuntos
Obstrução das Vias Respiratórias , Osteogênese por Distração , Síndrome de Pierre Robin , Apneia Obstrutiva do Sono , Lactente , Recém-Nascido , Humanos , Seguimentos , Síndrome de Pierre Robin/terapia , Resultado do Tratamento , Mandíbula/cirurgia , Obstrução das Vias Respiratórias/cirurgia , Estudos Retrospectivos
13.
Ann Surg ; 277(1): e5-e7, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35916142
14.
Brain Pathol ; 33(1): e13099, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35698024

RESUMO

Cerebral ischemia is the leading cause for long-term disability and mortality in adults due to massive neuronal death. Currently, there is no pharmacological treatment available to limit progressive neuronal death after stroke. A major mechanism causing ischemia-induced neuronal death is the excessive release of glutamate and the associated overexcitation of neurons (excitotoxicity). Normally, GABAB receptors control neuronal excitability in the brain via prolonged inhibition. However, excitotoxic conditions rapidly downregulate GABAB receptors via a CaMKII-mediated mechanism and thereby diminish adequate inhibition that could counteract neuronal overexcitation and neuronal death. To prevent the deleterious downregulation of GABAB receptors, we developed a cell-penetrating synthetic peptide (R1-Pep) that inhibits the interaction of GABAB receptors with CaMKII. Administration of this peptide to cultured cortical neurons exposed to excitotoxic conditions restored cell surface expression and function of GABAB receptors. R1-Pep did not affect CaMKII expression or activity but prevented its T286 autophosphorylation that renders it autonomously and persistently active. Moreover, R1-Pep counteracted the aberrant downregulation of G protein-coupled inwardly rectifying K+ channels and the upregulation of N-type voltage-gated Ca2+ channels, the main effectors of GABAB receptors. The restoration of GABAB receptors activated the Akt survival pathway and inhibited excitotoxic neuronal death with a wide time window in cultured neurons. Restoration of GABAB receptors and neuroprotective activity of R1-Pep was verified by using brain slices prepared from mice after middle cerebral artery occlusion (MCAO). Treatment with R1-Pep restored normal GABAB receptor expression and GABA receptor-mediated K+ channel currents. This reduced MCAO-induced neuronal excitability and inhibited neuronal death. These results support the hypothesis that restoration of GABAB receptor expression under excitatory conditions provides neuroprotection and might be the basis for the development of a selective intervention to inhibit progressive neuronal death after ischemic stroke.


Assuntos
Isquemia Encefálica , Receptores de GABA-B , Camundongos , Animais , Receptores de GABA-B/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto Cerebral , Peptídeos , Encéfalo/metabolismo , Ácido gama-Aminobutírico/metabolismo
15.
Laryngoscope ; 133(9): 2292-2300, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36453533

RESUMO

OBJECTIVE(S): To quantify the effect of laryngeal prominence size on socially perceived attributes relating to gender expression. Chondrolaryngoplasty ("tracheal shave") is a common procedure performed for transgender women to feminize neck appearance. The extent of thyroid cartilage resection needed to convey socially-perceived feminine gender expression without destabilizing the voice is incompletely understood. METHODS: Cross-sectional evaluation of a randomized allocation of images of varying laryngeal prominence to a non-repeated, random sample from November 2021 to December 2021. Photos of laryngeal prominence were isolated against a constant neck baseline with lateral, oblique, and frontal views. The images were embedded into a web-based survey with visual analog scales to capture perceived scaled gender expression (masculinity, femininity) and social traits (e.g., attractiveness, friendliness, leadership). We performed bivariate and multivariate analyses relating the laryngeal prominence to perceived gender expression and social traits. RESULTS: The analytic sample included 1,026 respondents. Laryngeal grades similar to the demonstrated "grade M" in this study and smaller demonstrated similar perceptions of increased femininity and decreased masculinity. Grades larger than M demonstrate significantly increased perceived masculinity and significantly decreased perceived femininity. The lateral and oblique views of the neck appear to be the most gender-informative. CONCLUSION: This crowd-sourced analysis of external laryngeal anatomy by a large population of observers provides clear, reproducible insights into social perceptions of gender identity and specifically femininity. These data will meaningfully inform patient counseling and surgical planning for gender-affirming interventions by establishing normative data representing the general public's perceptions. LEVEL OF EVIDENCE: NA Laryngoscope, 133:2292-2300, 2023.


Assuntos
Identidade de Gênero , Masculinidade , Masculino , Humanos , Feminino , Estudos Transversais , Percepção Social , Inquéritos e Questionários , Internet
16.
JTCVS Tech ; 16: 231-236, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36510525

RESUMO

Objective: Slide tracheoplasty is the standard technique to repair congenital long-segment tracheal stenosis. This operation most commonly requires median sternotomy, which has drawbacks in young children. We hypothesized that a transcervical approach without sternotomy would be feasible if done with a single-port robotic system. Methods: This proof-of concept study was performed in 2 small adult cadavers using a single-port robotic surgical system via a small neck incision. Relevant information, including operative time and details of operative technique, were recorded. Results: Long-segment slide tracheoplasty was completed successfully in 2 cadavers using a small neck incision and a single-port robotic surgical system. Strengths and pitfalls of the technique were identified, including technical refinements from the first attempt to the second. Operative time for robotic mobilization, incision, and anastomosis of the trachea was comparable to standard open approaches. Conclusions: Small-incision transcervical slide tracheoplasty, assisted by a single-port surgical robotic system, is feasible in a human cadaver. More work is needed to determine safety and applicability in live patients, particularly in children.

17.
Front Mol Neurosci ; 15: 1015906, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311027

RESUMO

One major factor regulating the strength of GABA B receptor signaling and thereby neuronal excitability is the dynamic control of their cell surface expression. GABA B receptors are constitutively internalized and recycled back to the plasma membrane to maintain a stable number of receptors at cell surface for appropriate signaling. Protein phosphatase 2A (PP2A) dependent dephosphorylation of serine 783 (S783) in the GABA B2 subunit is a key event for downregulating GABA B receptor cell surface expression particularly under conditions associated with excitotoxicity. Here, we investigated the role of PP2A in regulating GABA B receptor cell surface expression under physiological and excitotoxic conditions. For this purpose, we developed an interfering peptide (PP2A-Pep) that inhibits the interaction of GABA B receptors with PP2A. Using cultured cortical neurons, we found that PP2A downregulates GABA B receptor cell surface expression by inhibiting recycling of the receptors and thereby promoting degradation of the receptors. Inhibition of the GABA B receptor/PP2A interaction by PP2A-Pep in cultured cortical neurons restored GABA B receptor cell surface expression after excitotoxic stress and inhibited progressing neuronal death even when added 48 h after the insult. To explore the therapeutic potential of PP2A-Pep, we further analyzed effect of PP2A-Pep in the middle cerebral artery occlusion (MCAO) mouse model of cerebral ischemia. Incubation of brain slices prepared from MCAO-treated mice with PP2A-Pep restored normal GABA B receptor expression and GABA B receptor-mediated inhibition, reduced ischemic-induced overexcitability of neurons, and prevented neuronal death in the ischemic penumbra. This data illustrates the crucial role of regulating GABA B receptor phosphorylation by PP2A for controlling neuronal inhibition and excitability. The results further suggest that interfering with the GABA B receptor/PP2A interaction is a promising strategy for the development of specific therapeutic interventions to treat neurological diseases associated with a disturbed excitation/inhibition balance and downregulation of GABA B receptors.

18.
Med Oncol ; 39(12): 247, 2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36209296

RESUMO

Cancer cells rewire the metabolic processes beneficial for cancer cell proliferation, survival, and their progression. In this study, metabolic processes related to glucose, glutamine, and fatty acid metabolism signatures were collected from the molecular signatures database and investigated in the context of energy metabolic pathways through available genome-wide expression profiles of liver cancer cohorts by gene sets-based pathway activation scoring analysis. The outcomes of this study portray that the fatty acid metabolism, transport, and its storage related signatures are highly expressed across early stages of liver tumors and on the contrary, the gene sets related to glucose transport and glucose metabolism are prominently activated in the hepatocellular carcinoma (HCC) stage. Based on the results, these metabolic pathways are clearly dysregulated across specific stages of carcinogenesis. The identified dimorphic metabolic pathway dysregulation patterns are further reconfirmed by examining corresponding metabolic pathway genes expression patterns across various stages encompassing profiles. Recurrence is the primary concern in the carcinogenesis of liver tumors due to liver tissues regeneration. Hence, to further explore these dysregulation effects on recurrent cirrhosis and recurrent HCC sample containing profile GSE20140 was examined and interestingly, this result also reiterated these differential metabolic pathways dysregulation. In addition, a recently established metabolome profile for the massive panel of cancer cell-lines, including liver cancer cell-lines, was used for further exploration. These findings also reassured those differential metabolites abundance of the fatty acid and glucose metabolic pathways enlighten those dimorphic metabolic pathways dysregulation. Moreover, ROC curves of fatty acid metabolic pathway genes such as acetyl-CoA carboxylase (ACACB), acyl-CoA dehydrogenase long chain (ACADL), and acyl-CoA dehydrogenase medium chain (ACADM) as well as glucose metabolic pathway genes such as phosphoglycerate kinase (PGK1), pyruvate dehydrogenase (PDHA1), pyruvate dehydrogenase kinase (PDK1) demonstrated greater sensitivity and specificity in the corresponding stage-specific tumors with significant p-values (p < 0.05). Furthermore, overall survival (OS) and recurrence-free survival (RFS) studies also reconfirmed that the rate-limiting genes expression of fatty acid and glucose metabolic pathways reveal better and poor survival in HCC patient cohorts, respectively. In conclusion, all these results clearly show that metabolic rewiring and the existence of two diverse metabolic pathways dysregulation involving fatty acid and glucose metabolism across the stages of liver tumors have been identified. These findings might be useful for developing therapeutic target treatments in stage-specific tumors.


Assuntos
Acil-CoA Desidrogenases , Carcinoma Hepatocelular , Neoplasias Hepáticas , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Acil-CoA Desidrogenases/metabolismo , Carcinogênese , Carcinoma Hepatocelular/patologia , Ácidos Graxos/metabolismo , Glucose/metabolismo , Glutamina/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Redes e Vias Metabólicas , Oxirredutases , Fosfoglicerato Quinase/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , Piruvatos
19.
Int J Pediatr Otorhinolaryngol ; 161: 111251, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35988373

RESUMO

OBJECTIVES: To outline an expert-based consensus of recommendations for the diagnosis and management of pediatric patients with congenital tracheal stenosis. METHODS: Expert opinions were sought from members of the International Pediatric Otolaryngology Group (IPOG) via completion of an 18-item survey utilizing an iterative Delphi method and review of the literature. RESULTS: Forty-three members completed the survey providing recommendations regarding the initial history, clinical evaluation, diagnostic evaluation, temporizing measures, definitive repair, and post-repair care of children with congenital tracheal stenosis. CONCLUSION: These recommendations are intended to be used to support clinical decision-making regarding the evaluation and management of children with congenital tracheal stenosis. Responses highlight the diverse management strategies and the importance of a multidisciplinary approach to care of these patients.


Assuntos
Otolaringologia , Procedimentos de Cirurgia Plástica , Criança , Consenso , Constrição Patológica , Humanos , Lactente , Procedimentos de Cirurgia Plástica/métodos , Traqueia/anormalidades , Traqueia/cirurgia , Estenose Traqueal/congênito , Resultado do Tratamento
20.
Am J Otolaryngol ; 43(5): 103526, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35717857

RESUMO

OBJECTIVES/HYPOTHESIS: To determine the effects of the COVID-19 pandemic on Adenotonsillectomies (TA), Tonsil Related Cases (TC), and Peritonsillar Abscess (PTA) Trends. STUDY DESIGN: Retrospective Cohort Study. METHODS: This is a retrospective cohort study using the Pediatric Health Information System® (PHIS) database, which consists of 51 children's hospitals. Regions were defined according to PHIS rules with at least five children's hospitals per region. We compared monthly total TA, TC, TC as a proportion of all hospital visits, and PTA from all encounters at each hospital from January 1, 2019, through December 31, 2021. RESULTS: Compared to 2019, April 2020 saw mean TC drop significantly from 371.62 to 68.37 (p < 0.001). Interestingly, June, September, and December 2020 had significantly higher mean TC compared to 2019. TC as a proportion of all hospital visits decreased significantly throughout the majority of 2021. Similarly, TA significantly decreased during 2020 and 2021 across all regions in the US, starting in March 2020 and this reduction in TA extended through the end of 2021 without any signs of recovery. PTA rates did not change significantly over the three years. CONCLUSIONS: The pandemic-plagued 2020 saw a noticeable decrease in overall TC and TA but then rebounded quickly to even higher than pre-pandemic levels. However, this rebound halted for the majority of 2021 and subsequently decreased to lower than pre-pandemic levels, which differs from other communicable pathologies such as otitis media which decreased initially then recovered to pre-pandemic levels by Summer of 2021.


Assuntos
COVID-19 , Otolaringologia , Abscesso Peritonsilar , COVID-19/epidemiologia , Criança , Humanos , Tonsila Palatina , Pandemias , Abscesso Peritonsilar/diagnóstico , Abscesso Peritonsilar/epidemiologia , Estudos Retrospectivos
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