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United States neurological surgery residency education has undergone substantive changes over the past 2 decades. Neurosurgical professional bodies have developed numerous initiatives providing standardized assessments and training opportunities for residency programs. However, there have been few studies using standardized measures to assess core components of educational programming in individual programs. We conducted a 12-year retrospective review of resident American Board of Neurological Surgery (ABNS) board scores using our institutional data from 2010 to 2021 to determine the effect of introducing a weekly didactic resident education hour (REH) on resident scores in the ABNS written in-training examination. ABNS scaled scores were analyzed before (2010-2016) and after (2017-2021) REH introduction. To account for a practice effect, we used a 2-factor linear regression model with an interaction term. We obtained ABNS scores from 43 residents representing 132 test attempts. The average ABNS scaled score significantly improved after the introduction of REH (319 vs 410, t = -3.44, P = .0008). Accounting for the practice effect revealed a significant interaction effect between the number of attempts taking the ABNS examination and whether formal didactics were taught, accounting for 46.2 points on the examination (t = 2.309, P = .023); however, REH alone did not have a significant effect on the scaled scores (t = -1.649, P = .102). ABNS written board scores represent a standardized metric by which educational initiatives within training programs may be assessed for efficacy. Further research is needed to identify educational approaches that are effective to meet the goal of demonstrated mastery of fundamental knowledge in neurosurgery across a diversity of neurological surgery residency programs.
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Pseudomonas aeruginosa is a highly adaptable opportunistic pathogen capable of exploiting barriers and immune defects to cause chronic lung infections in conditions such as cystic fibrosis. In these contexts, host immune responses are ineffective at clearing persistent bacterial infection, instead driving a cycle of inflammatory lung damage. This review outlines key components of the host immune response to chronic P. aeruginosa infection within the lung, beginning with initial pathogen recognition, followed by a robust yet maladaptive innate immune response, and an ineffective adaptive immune response that propagates lung damage while permitting bacterial persistence. Untangling the interplay between host immunity and chronic P. aeruginosa infection will allow for the development and refinement of strategies to modulate immune-associated lung damage and potentiate the immune system to combat chronic infection more effectively.
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Interações Hospedeiro-Patógeno , Imunidade Inata , Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/imunologia , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Doença Crônica , Animais , Interações Hospedeiro-Patógeno/imunologia , Imunidade Adaptativa , Pneumopatias/imunologia , Pneumopatias/microbiologia , Fibrose Cística/imunologia , Fibrose Cística/microbiologia , Fibrose Cística/complicações , Pulmão/imunologia , Pulmão/microbiologiaRESUMO
The 78-kDa glucose regulated protein (GRP78) commonly upregulated in a wide variety of tumors is an important prognostic marker and a promising target for suppressing tumorigenesis and treatment resistance. While GRP78 is well established as a major endoplasmic reticulum (ER) chaperone with anti-apoptotic properties and a master regulator of the unfolded protein response, its new role as a regulator of oncoprotein expression is just emerging. MYC is dysregulated in about 70 % of human cancers and is the most commonly activated oncoprotein. However, despite recent advances, therapeutic targeting of MYC remains challenging. Here we identify GRP78 as a new target for suppression of MYC expression. Using multiple MYC-dependent cancer models including head and neck squamous cell carcinoma and their cisplatin-resistant clones, breast and pancreatic adenocarcinoma, our studies revealed that GRP78 knockdown by siRNA or inhibition of its activity by small molecule inhibitors (YUM70 or HA15) reduced c-MYC expression, leading to onset of apoptosis and loss of cell viability. This was observed in 2D cell culture, 3D spheroid and in xenograft models. Mechanistically, we determined that the suppression of c-MYC is at the post-transcriptional level and that YUM70 and HA15 treatment potently upregulated the eukaryotic translation inhibitor 4E-BP1, which targets eIF4E critical for c-MYC translation initiation. Furthermore, knock-down of 4E-BP1 via siRNA rescued YUM70-mediated c-MYC suppression. As YUM70 is also capable of suppressing N-MYC expression, this study offers a new approach to suppress MYC protein expression through knockdown or inhibition of GRP78.
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Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Ciclo Celular , Chaperona BiP do Retículo Endoplasmático , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico , Proteínas Proto-Oncogênicas c-myc , Humanos , Chaperona BiP do Retículo Endoplasmático/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/antagonistas & inibidores , Camundongos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Regulação para Cima/efeitos dos fármacosRESUMO
OBJECTIVE: As many as 5% of normocephalic children may have a prematurely fused sagittal suture, yet the clinical significance and best course of management of this finding remain unclear. Providers in the Synostosis Research Group were surveyed to create a multicenter consensus on an optimal treatment and monitoring algorithm for this condition. METHODS: A four-round modified Delphi method was utilized. The first two rounds consisted of anonymous surveys distributed to 10 neurosurgeons and 9 plastic surgeons with expertise in craniosynostosis across 9 institutions, and presented 3 patients (aged 3 years, 2 years, and 2 months) with incidentally discovered fused sagittal sutures, normal cephalic indices, and no parietal dysmorphology. Surgeons were queried about their preferred term for this entity and how best to manage these patients. Results were synthesized to create a treatment algorithm. The third and fourth feedback rounds consisted of open discussion of the algorithm until no further concerns arose. RESULTS: Most surgeons preferred the term "premature fusion of the sagittal suture" (93%). At the conclusion of the final round, all surgeons agreed to not operate on the 3- and 2-year-old patients unless symptoms of intracranial hypertension or papilledema were present. In contrast, 50% preferred to operate on the 2-month-old. However, all agreed to utilize shared decision-making, taking into account any concerns about future head shape and neurodevelopment. Panelists agreed that patients over 18 months of age without signs or symptoms suggesting elevated intracranial pressure (ICP) should not undergo surgical treatment. CONCLUSIONS: Through the Delphi method, a consensus regarding management of premature fusion of the sagittal suture was obtained from a panel of North American craniofacial surgeons. Without signs or symptoms of ICP elevation, surgery is not recommended in patients over 18 months of age. However, for children younger than 18 months, surgery should be discussed with caregivers using a shared decision-making process.
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Suturas Cranianas , Craniossinostoses , Técnica Delphi , Achados Incidentais , Humanos , Craniossinostoses/cirurgia , Suturas Cranianas/cirurgia , Pré-Escolar , Feminino , Masculino , Lactente , Neurocirurgiões , AlgoritmosRESUMO
PURPOSE: Clinical sequencing of tumor DNA is necessary to render an integrated diagnosis and select therapy for children with primary central nervous system (CNS) tumors, but neurosurgical biopsy is not without risk. In this study, we describe cell-free DNA (cfDNA) in blood and cerebrospinal fluid (CSF) as sources for "liquid biopsy" in pediatric brain tumors. METHODS: CSF samples were collected by lumbar puncture, ventriculostomy, or surgery from pediatric patients with CNS tumors. Following extraction, CSF-derived cfDNA was sequenced using UW-OncoPlex™, a clinically validated next-generation sequencing platform. CSF-derived cfDNA results and paired plasma and tumor samples concordance was also evaluated. RESULTS: Seventeen CSF samples were obtained from 15 pediatric patients with primary CNS tumors. Tumor types included medulloblastoma (n = 7), atypical teratoid/rhabdoid tumor (n = 2), diffuse midline glioma with H3 K27 alteration (n = 4), pilocytic astrocytoma (n = 1), and pleomorphic xanthoastrocytoma (n = 1). CSF-derived cfDNA was detected in 9/17 (53%) of samples, and sufficient for sequencing in 8/10 (80%) of extracted samples. All somatic mutations and copy-number variants were also detected in matched tumor tissue, and tumor-derived cfDNA was absent in plasma samples and controls. Tumor-derived cfDNA alterations were detected in the absence of cytological evidence of malignant cells in as little as 200 µl of CSF. Several clinically relevant alterations, including a KIAA1549::BRAF fusion were detected. CONCLUSIONS: Clinically relevant genomic alterations are detectable using CSF-derived cfDNA across a range of pediatric brain tumors. Next-generation sequencing platforms are capable of producing a high yield of DNA alterations with 100% concordance rate with tissue analysis.
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Biomarcadores Tumorais , Neoplasias Encefálicas , DNA Tumoral Circulante , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Criança , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/diagnóstico , Masculino , Feminino , Pré-Escolar , Adolescente , Lactente , DNA Tumoral Circulante/líquido cefalorraquidiano , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/líquido cefalorraquidiano , Ácidos Nucleicos Livres/líquido cefalorraquidiano , Ácidos Nucleicos Livres/genética , Ácidos Nucleicos Livres/sangue , Biópsia Líquida/métodos , MutaçãoRESUMO
PURPOSE: Oral adjuvant endocrine therapy (AET) is an effective treatment for hormone receptor positive breast cancer to decrease recurrence and mortality, but adherence is poor. This study explored post-menopausal women's experiences with AET, with a particular focus on adherence to AET as well as distress and symptoms experienced prior to and during AET treatment. METHODS: Participants were recruited from a hospital registry, stratified by adherence to/discontinuation of AET. Telephone interviews followed a semi-structured interview guide and were recorded and transcribed verbatim. Transcripts were systematically coded using team-based coding, with analysis of themes using a grounded theory approach. RESULTS: Thirty-three participants were interviewed; ages ranged from 57 to 86 years. Participants included 10 discontinued patients and 23 patients who completed their AET course or were adherent to AET at the time of interviewing. Both adherent and discontinued patients reported symptoms throughout their AET treatment course, and both attributed symptoms to factors other than AET (e.g., older age and pre-existing comorbidities). However, discontinued patients were more likely to attribute symptoms to AET and to describe difficulty managing their symptoms, with some directly citing symptoms as the reason for discontinuing AET therapy. Conversely, adherent patients were more likely to describe the necessity of taking AET, despite symptoms. CONCLUSIONS: AET adherence was associated with beliefs about AET, symptom attribution, and symptom management. Routine symptom monitoring during AET and addressing both symptoms and patients' understanding of their symptoms may promote adherence to AET.
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Neoplasias da Mama , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Pós-Menopausa , Adesão à Medicação , Antineoplásicos Hormonais/uso terapêuticoRESUMO
Purpose: Somatic molecular profiling of pediatric brain tumors aids with the diagnosis and treatment of patients with a variety of high- and low-grade central nervous system neoplasms. Here, we report follow-up targeted germline evaluation for patients with possible germline variants following tumor only testing in the initial year in which somatic molecular testing was implemented at a single institution. Patients and Methods: Somatic testing was completed for all tumors of the central nervous system (CNS) undergoing diagnostic workup at Seattle Children's Hospital during the study period of November 2015 to November 2016. Sequencing was performed in a College of American Pathologists-accredited, Clinical Laboratory Improvements Amendments-certified laboratory using UW-OncoPlex™ assay (version 5), a DNA-based targeted next generation sequencing panel validated to detect genetic alterations in 262 cancer-related genes. We tracked subsequent clinical evaluation and testing on a subgroup of this cohort found to have potential germline variants of interest. Results: Molecular sequencing of 88 patients' tumors identified 31 patients with variants that warranted consideration of germline testing. To date, 19 (61%) patients have been tested. Testing confirmed germline variants for ten patients (31% of those identified for testing), one with two germline variants (NF1 and mosaic TP53). Eight (26%) patients died before germline testing was sent. One patient (13%) has not yet had testing. Conclusion: Clinically validated molecular profiling of pediatric brain tumors identifies patients who warrant further germline evaluation. Despite this, only a subset of these patients underwent the indicated confirmatory sequencing. Further work is needed to identify barriers and facilitators to this testing, including the role of genetic counseling and consideration of upfront paired somatic-germline testing.
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Pediatric orbital and skull base pathologies encompass a spectrum of inflammatory, sporadic, syndromic, and neoplastic processes that require a broad and complex clinical approach for both medical and surgical treatment. Given their complexity and often multicompartment involvement, a multidisciplinary approach for diagnosis, patient and family counseling, and ultimately treatment provides the best patient satisfaction and clinical outcomes. Advances in minimally invasive surgical approaches, including endoscopic endonasal and transorbital approaches allows for more targeted surgical approaches through smaller corridors beyond more classic transcranial or transracial approaches.
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Base do Crânio , Humanos , Criança , Base do Crânio/cirurgia , Doenças Orbitárias/cirurgia , Neoplasias da Base do Crânio/cirurgia , Endoscopia/métodos , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
PURPOSE: To review patient-reported outcomes (PROs) and survivorship in patients undergoing osteochondral autograft or allograft transplantation (OAT) of the femoral head. METHODS: PubMed, Cochrane Center for Register of Controlled Trials, and Scopus databases were searched in November 2022 with an updated search extending to December 2023 using criteria from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the following keywords: (hip OR femoral head) AND (mosaicplasty OR osteochondral allograft OR osteochondral autograft OR osteochondral lesion). Articles were included if they evaluated postoperative PROs in patients who underwent OAT of the femoral head and had a study size of 5 or more hips (n ≥ 5). Survivorship was defined as freedom from conversion to total hip arthroplasty. For PROs evaluated in 3 studies or more, forest plots were created and I2 was calculated. RESULTS: Twelve studies were included in this review, with a total of 156 hips and a mean follow-up time ranging between 16.8 and 222 months. In total, 104 (66.7%) hips were male while 52 (33.3%) were female. Age of patients ranged from 17.0 to 35.4 years, while body mass index ranged from 23.3 to 28.1. Eight studies reported on osteochondral autograft transplantation and 4 studies on osteochondral allograft transplantation. Three studies reported significant improvement in at least 1 PRO. Survivorship ranged from 61.5% to 96% at minimum 2-year follow-up and from 57.1% to 91% at minimum 5-year follow-up. At a follow-up of less than 5 years, osteochondral allograft transplantation studies showed 70% to 87.5% survivorship, while autograft varied from 61.54% to 96%. CONCLUSIONS: Patients with osteochondral lesions of the femoral head who underwent osteochondral autograft or allograft transplantation demonstrated improved PROs but variable survivorship rates. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.
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Importance: Appendicitis is the most common indication for urgent surgery in the pediatric population, presenting across a range of severity and with variable complications. Differentiating simple appendicitis (SA) and perforated appendicitis (PA) on presentation may help direct further diagnostic workup and appropriate therapy selection, including antibiotic choice and timing of surgery. Objective: To provide a mechanistic understanding of the differences in disease severity of appendicitis with the objective of developing improved diagnostics and treatments, specifically for the pediatric population. Design, Setting, and Participants: The Gene Expression Profiling of Pediatric Appendicitis (GEPPA) study was a single-center prospective exploratory diagnostic study with transcriptomic profiling of peripheral blood collected from a cohort of children aged 5 to 17 years with abdominal pain and suspected appendicitis between November 2016 and April 2017 at the Alberta Children's Hospital in Calgary, Alberta, Canada, with data analysis reported in August 2023. There was no patient follow-up in this study. Exposure: SA, PA, or nonappendicitis abdominal pain. Main Outcomes and Measures: Blood transcriptomics was used to develop a hypothesis of underlying mechanistic differences between SA and PA to build mechanistic hypotheses and blood-based diagnostics. Results: Seventy-one children (mean [SD] age, 11.8 [3.0] years; 48 [67.6%] male) presenting to the emergency department with abdominal pain and suspected appendicitis were investigated using whole-blood transcriptomics. A central role for immune system pathways was revealed in PA, including a dampening of major innate interferon responses. Gene expression changes in patients with PA were consistent with downregulation of immune response and inflammation pathways and shared similarities with gene expression signatures derived from patients with sepsis, including the most severe sepsis endotypes. Despite the challenges in identifying early biomarkers of severe appendicitis, a 4-gene signature that was predictive of PA compared to SA, with an accuracy of 85.7% (95% CI, 72.8-94.1) was identified. Conclusions: This study found that PA was complicated by a dysregulated immune response. This finding should inform improved diagnostics of severity, early management strategies, and prevention of further postsurgical complications.
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Apendicite , Sepse , Criança , Humanos , Masculino , Feminino , Apendicite/diagnóstico , Apendicite/genética , Estudos Prospectivos , Marcadores Genéticos , Perfilação da Expressão Gênica , Alberta , Dor Abdominal/genéticaRESUMO
INTRODUCTION: Receptor-interacting protein kinase 1 (RIPK1), a key mediator of inflammation through necroptosis and proinflammatory cytokine production, may play a role in the pathogenesis of immune-mediated inflammatory diseases such as chronic plaque psoriasis. An experimental medicine study of RIPK1 inhibition with GSK2982772 immediate-release formulation at doses up to 60 mg three times daily in mild to moderate plaque psoriasis indicated that efficacy may be improved with higher trough concentrations of GSK2982772. METHODS: This multicenter, randomized, double-blind, placebo-controlled, repeat-dose study (NCT04316585) assessed the efficacy, safety, pharmacokinetics, and pharmacodynamics of 960 mg GSK2982772 (once-daily modified-release formulation) in patients with moderate to severe plaque psoriasis. Twenty-nine patients were randomized 2:1 to GSK2982772 (N = 19) or placebo (N = 10) for 12 weeks. RESULTS: GSK2982772 was well tolerated with trough concentrations greater than tenfold higher than the previous phase 1 study with immediate release. Despite near complete RIPK1 target engagement in blood and modest reduction in circulating inflammatory cytokines, the proportion of patients achieving 75% improvement from baseline in Psoriasis Area Severity Index score at week 12 was similar between GSK2982772 and placebo (posterior median 1.8% vs 4.9%, respectively), with an estimated median treatment difference of - 2.3%. This analysis incorporated historical placebo data through the use of an informative prior distribution on the placebo arm. Week 4 changes in skin biopsy gene expression suggested sufficient local drug exposure to elicit a pharmacodynamic response. CONCLUSION: Administration of the RIPK1 inhibitor GSK2982772 to patients with moderate to severe plaque psoriasis did not translate into meaningful clinical improvements.
Psoriasis is thought to be caused by problems with the immune system, including possibly receptor-interacting protein kinase 1 (RIPK1), which plays an important role in the development of inflammation. A previous study suggested that the drug, GSK2982772, which interferes with RIPK1, might improve symptoms in patients with psoriasis. This study examined whether higher doses of GSK2982772 than previously studied would be beneficial for patients with psoriasis. The study found that the severity of psoriasis was similar in patients treated with GSK2982772 for 12 weeks as in those who did not receive the drug, indicating that GSK298772 did not improve psoriasis.
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OBJECTIVE: Spina bifida represents one of the most common birth defects, occurring in approximately 1-2 children per 1000 live births worldwide. The functional level of patients with spina bifida is highly variable and believed to be correlated with the anatomical level of the lesion. The variable clinical picture is well established, but the correlation with anatomical level and intraoperative neuromonitoring (IONM) data has not been investigated. Furthermore, the potential for preserving function beyond the apparent clinical level has also not been investigated. The objective of this research was to determine the presence and level of intraoperative transcranial motor evoked potential (tcMEP) and triggered electromyography (tEMG) responses, and the association of these responses with preoperative clinical function and radiographic data in pediatric cases of complex tethered cord release reoperations. METHODS: A single-center retrospective review of pediatric patients with complex spinal dysraphism undergoing detethering reoperations was conducted. Preoperative demographic and clinical data, including the radiographic and clinical level of dysraphism, were collected. IONM, including tcMEPs and tEMG responses, were obtained and compared with preoperative clinical data. Descriptive analysis was performed, by patient for demographics and by case for surgeries performed. RESULTS: In 100% of 21 cases of complex detethering reoperations, representing 20 patients, intraoperative tcMEPs could be generated at (4.8%) or below (95.2%) the level of clinical function. Compared with the preoperative clinical examination, 5 cases (23.8%) demonstrated tcMEP responses that were 1 level below the clinical function level, 11 cases (52.4%) were 2 levels below, and 4 cases (19.0%) were 3 levels below. Overall, 18 of 21 cases showed tEMG responses at or below the level of clinical function; of these, 7 cases (33%) were 1 level below and 3 (14%) were ≥ 2 levels below the clinical function level. CONCLUSIONS: The presence of positive stimulation potentials below the level of clinical function in patients with complex spinal dysraphism undergoing detethering reoperations indicates a degree of preserved neuronal connectivity. These findings suggest novel future treatment approaches for these patients, including using devices targeted to stimulation of these neurological pathways.
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Eletromiografia , Potencial Evocado Motor , Monitorização Neurofisiológica Intraoperatória , Reoperação , Disrafismo Espinal , Humanos , Masculino , Feminino , Pré-Escolar , Estudos Retrospectivos , Criança , Disrafismo Espinal/cirurgia , Disrafismo Espinal/diagnóstico por imagem , Potencial Evocado Motor/fisiologia , Monitorização Neurofisiológica Intraoperatória/métodos , Lactente , Defeitos do Tubo Neural/cirurgia , Defeitos do Tubo Neural/fisiopatologia , Adolescente , Procedimentos Neurocirúrgicos/métodosRESUMO
Somatic versus Germline-A Case Series of Three Children with ATM- mutated Medulloblastoma.
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Neoplasias Cerebelares , Meduloblastoma , Criança , Humanos , Meduloblastoma/diagnóstico , Meduloblastoma/genética , Meduloblastoma/terapia , Mutação em Linhagem Germinativa/genética , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/genética , Proteínas Mutadas de Ataxia Telangiectasia/genéticaRESUMO
OBJECTIVE: To review cases of congenital frontonasal dermoids to gain insight into the accuracy of preoperative computed tomography (CT) and magnetic resonance imaging (MRI) in predicting intracranial extension. METHODS: This retrospective study included all patients who underwent primary excision of frontonasal dermoids at an academic children's hospital over a 23-year period. Preoperative presentation, imaging, and operative findings were reviewed. Receiver operating characteristic (ROC) statistics were generated to determine CT and MRI accuracy in detecting intracranial extension. RESULTS: Search queries yielded 129 patients who underwent surgical removal of frontonasal dermoids over the study period with an average age of presentation of 12 months. Preoperative imaging was performed on 122 patients, with 19 patients receiving both CT and MRI. CT and MRI were concordant in the prediction of intracranial extension in 18 out of 19 patients. Intraoperatively, intracranial extension requiring craniotomy was seen in 11 patients (8.5%). CT was 87.5% sensitive and 97.4% specific for predicting intracranial extension with an ROC of 0.925 (95% CI [0.801, 1]), whereas MRI was 60.0% sensitive and 97.8% specific with an ROC of 0.789 (95% CI [0.627, 0.950]). CONCLUSION: This is the largest case series in the literature describing a single institution's experience with frontonasal dermoids. Intracranial extension is rare and few patients required craniotomy in our series. CT and MRI have comparable accuracy at detecting intracranial extension. Single-modality imaging is recommended preoperatively in the absence of other clinical indications. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1961-1966, 2024.
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Cisto Dermoide , Neoplasias Nasais , Criança , Humanos , Lactente , Cisto Dermoide/diagnóstico por imagem , Cisto Dermoide/cirurgia , Imageamento por Ressonância Magnética , Neoplasias Nasais/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Traffic-related air pollution (TRAP) exposure is associated with systemic health effects, which can be studied using blood-based markers. Although we have previously shown that high TRAP concentrations alter the plasma proteome, the concentration-response relationship between blood proteins and TRAP is unexplored in controlled human exposure studies. We aimed to identify concentration-dependent plasma markers of diesel exhaust (DE), a model of TRAP. Fifteen healthy non-smokers were enrolled into a double-blinded, crossover study where they were exposed to filtered air (FA) and DE at 20, 50 and 150 µg/m3 PM2.5 for 4h, separated by ≥ 4-week washouts. We collected blood at 24h post-exposure and used label-free mass spectrometry to quantify proteins in plasma. Proteins exhibiting a concentration-response, as determined by linear mixed effects models (LMEMs), were assessed for pathway enrichment using WebGestalt. Top candidates, identified by sparse partial least squares discriminant analysis and LMEMs, were confirmed using enzyme-linked immunoassays. Thereafter, we assessed correlations between proteins that showed a DE concentration-response and acute inflammatory endpoints, forced expiratory volume in 1 s (FEV1) and methacholine provocation concentration causing a 20% drop in FEV1 (PC20). DE exposure was associated with concentration-dependent alterations in 45 proteins, which were enriched in complement pathways. Of the 9 proteins selected for confirmatory immunoassays, based on complementary bioinformatic approaches to narrow targets and availability of high-quality assays, complement factor I (CFI) exhibited a significant concentration-dependent decrease (-0.02 µg/mL per µg/m3 of PM2.5, p = 0.04). Comparing to FA at discrete concentrations, CFI trended downward at 50 (-2.14 ± 1.18, p = 0.08) and significantly decreased at 150 µg/m3 PM2.5 (-2.93 ± 1.18, p = 0.02). CFI levels were correlated with FEV1, PC20 and nasal interleukin (IL)-6 and IL-1ß. This study details concentration-dependent alterations in the plasma proteome following DE exposure at concentrations relevant to occupational and community settings. CFI shows a robust concentration-response and association with established measures of airway function and inflammation.
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Poluentes Atmosféricos , Emissões de Veículos , Humanos , Emissões de Veículos/toxicidade , Emissões de Veículos/análise , Proteoma , Estudos Cross-Over , Testes de Função Respiratória , Interleucina-6 , Material Particulado/toxicidade , Material Particulado/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análiseRESUMO
PURPOSE: To review current literature evaluating patient-reported outcomes (PROs) and survivorship in patients undergoing revision hip arthroscopy with labral reconstruction or augmentation. METHODS: A systematic review was performed with the following key words: (revision) AND (hip OR femoroacetabular impingement) AND (arthroscopy OR arthroscopic) AND (reconstruction OR augmentation OR irreparable). PubMed, Cochrane Trials, and Scopus were queried in October 2022 using the criteria established in the Preferred Reporting Items for Systematic Reviews and Meta-analyses. Studies were included if they involved patients undergoing revision hip arthroscopy with labral reconstruction or augmentation and reported preoperative and postoperative PROs at minimum 2-year follow-up. Only original research articles were included. Survivorship was defined as a nonconversion to total hip arthroplasty. Outcomes present in 3 or more studies underwent further statistical analysis with forest plots. Heterogeneity of studies was evaluated using the I2 statistic. RESULTS: Five studies were reviewed, including 359 revision hip arthroscopies (335 with complete follow-up) with a follow-up that ranged from 2.2 to 5.2 years. Four studies reported on outcomes after revision labral reconstruction and 1 study reported on labral augmentation. Two out of 5 included studies evaluated for statistical significance between preoperative and postoperative outcomes. Three out of 5 studies reported a rate of at least 70% for achieving minimal clinically important difference in at least 1 PRO. At minimum 2-year follow-up, survivorship ranged from 93.5% to 100%. CONCLUSIONS: Patients that underwent revision hip arthroscopy with labral reconstruction or augmentation demonstrated improvement in PROs with mixed rates of achieving clinical benefit and rates of survivorship at minimum 2-year follow-up ranging from 93.5% to 100%. LEVEL OF EVIDENCE: Level IV, systematic review of level III to IV studies.
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Artroscopia , Medidas de Resultados Relatados pelo Paciente , Reoperação , Humanos , Reoperação/estatística & dados numéricos , Artroscopia/métodos , Impacto Femoroacetabular/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Articulação do Quadril/cirurgiaRESUMO
In prostate cancer, the bone is the most common site of metastasis, and it is essential to evaluate metastatic bone lesions to assess the tumor burden and treatment response. Castration-resistant prostate cancer refers to the state wherein the cancer continues to progress despite a significant reduction of the sex hormone level and is associated with frequent distant metastasis. The Prostate Cancer Working Group 3 (PCWG3) released guidelines that aimed to standardize the assessment of treatment effects in castration-resistant prostate cancer using bone scintigraphy. However, these guidelines can be challenging to comprehend and implement in practical settings. The purpose of this review was to provide an overview of a specific image acquisition method and treatment response assessment for bone scintigraphy-based evaluation of bone lesions in metastatic castration-resistant prostate cancer, in accordance with the PCWG3 guidelines.
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Traditional use of opioids to treat postoperative pain may lead to abuse and overdose. The development of Enhanced Recovery After Surgery (ERAS) protocols has helped to shift pain management from traditional methods to evidence-based best practices involving multimodal analgesia techniques. The purpose of this quality improvement project was to implement and determine the effectiveness of a standardized, evidence-based ERAS pain management pathway for patients undergoing colorectal or gynecology procedures at a medical center in Hawaii. After the intervention, the evaluation of data associated with opioid use, patients' pain scores, time spent in the postanesthesia care unit, and inpatient length of stay showed that most results were not significant. However, the ERAS pain management pathway did reduce clinical practice variations, intraoperative opioid administration, the time that patients spent in the postanesthesia care unit, and length of stay. The ERAS pain management pathway continues to be used and updated at this facility.
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Recuperação Pós-Cirúrgica Melhorada , Manejo da Dor , Humanos , Manejo da Dor/métodos , Havaí , Analgésicos Opioides/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Estudos Retrospectivos , Tempo de InternaçãoRESUMO
OBJECTIVE: Tethered cord syndrome refers to a constellation of symptoms characterized by neurological, musculoskeletal, and urinary symptoms, caused by traction on the spinal cord, which can be secondary to various etiologies. Surgical management of simple tethered cord etiologies (e.g., fatty filum) typically consists of a single-level lumbar laminectomy, intradural exploration, and coagulation and sectioning of the filum. More complex etiologies such as lipomyelomeningoceles or scar formation after myelomeningocele repair involve complex dissection and dural reconstruction. The purpose of this study was to evaluate operative complications and long-term outcomes of secondary retethering related to pediatric tethered cord release (TCR) at a tertiary children's hospital. METHODS: Medical records of children who underwent surgery for TCR from July 2014 to March 2023 were retrospectively reviewed. Data collected included demographics, perioperative characteristics, surgical technique, and follow-up duration. Primary outcomes were 60-day postoperative complications and secondary retethering requiring repeat TCR surgery. Univariate and multivariate analyses were performed to identify risk factors associated with complications and secondary retethering. RESULTS: A total of 363 TCR surgeries (146 simple, 217 complex) in 340 patients were identified. The mean follow-up was 442.8 ± 662.2 days for simple TCRs and 733.9 ± 750.3 days for complex TCRs. The adjusted 60-day complication-free survival rate was 96.3% (95% CI 91.3%-98.4%) for simple TCRs and 88.7% (95% CI 82.3%-91.4%) for complex TCRs. Lower weight, shorter surgical times, and intensive care unit admission were associated with complications for simple TCRs. Soft-tissue drains increased complications for complex TCRs. The secondary retethering rates were 1.4% for simple TCRs and 11.9% for complex TCRs. The 1-, 3-, and 5-year progression-free survival rates in complex cases were 94.7% (95% CI 89.1%-97.4%), 77.7% (95% CI 67.3%-85.3%), and 62.6% (95% CI 46.5%-75.1%), respectively. Multivariate analysis revealed that prior detethering (OR 8.15, 95% CI 2.33-28.50; p = 0.001) and use of the operative laser (OR 10.43, 95% CI 1.36-80.26; p = 0.024) were independently associated with secondary retethering in complex cases. CONCLUSIONS: This is the largest series to date examining postoperative complications and long-term secondary retethering in TCR surgery. Simple TCR surgeries demonstrated safety, rare complications, and low secondary retethering rates. Complex TCR surgeries presented higher risks of complications and secondary retethering. Modifiable risk factors such as operative laser use influenced secondary retethering in complex cases.
Assuntos
Defeitos do Tubo Neural , Procedimentos Neurocirúrgicos , Criança , Humanos , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Resultado do Tratamento , Defeitos do Tubo Neural/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Receptores de Antígenos de Linfócitos TRESUMO
INTRODUCTION: Bile acids have been implicated in gastric carcinogenesis. We hypothesized that bile acid sequestrant medication (BAM) use is associated with a lower gastric cancer (GC) incidence. METHODS: We assembled a cohort of veterans receiving longitudinal care within the Veterans Health Administration between 2000 and 2020 who completed testing for Helicobacterpylori . The index date was the date of completed H. pylori testing. The primary exposure was the number of filled BAM prescription(s) in the 5 years before the index date. The primary outcome was incident GC, stratified by anatomic subsite. Follow-up began at the index date and ended at the earliest of GC, death, after 2 years of follow-up, or the study end (May 31, 2020). We used Kaplan-Meier curves to visualize differences in GC incidence by exposure group and multivariable Cox proportional hazards models to estimate the association between BAM exposure and anatomic site-specific GC. RESULTS: Among 417,239 individuals (89% male, mean age 54 years, 63% non-Hispanic White), 4,916 (1.2%) filled at least one BAM prescription, 2,623 of whom filled ≥4. Compared with unexposed individuals, those with ≥4 BAM fills before entry had a lower incidence (adjusted hazard ratio 0.71; 95% confidence interval, 0.37-1.36) of GC, but confidence intervals were wide. Results were consistent irrespective of GC anatomic site. DISCUSSION: BAMs may have a protective effect against both cardia and noncardia GC. Further research and external validation are needed to confirm these findings.