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INTRODUCTION: Neuroblastoma (NB) is the most common extra-cranial malignancy in children. Poor survival in high-risk NB is attributed to recurrent metastatic disease. To better study metastatic disease, we used a novel mouse model to investigate differential gene expression between primary tumor cells and metastatic cells. We hypothesized that metastatic NB cells have a different gene expression profile from primary tumor cells and cultured cells. METHODS: Using three human NB cell lines (NGP, CHLA255, and SH-SY5Y), orthotopic xenografts were established in immunodeficient nod/scid gamma mice via subcapsular renal injection. Mice were sacrificed and NB cells were isolated from the primary tumor and from sites of metastasis (bone marrow, liver). RNA sequencing, gene set analysis, and pathway analysis were performed to identify differentially expressed genes and molecular pathways in the metastatic cells compared to primary tumor cells. RESULTS: There were 266 differentially expressed genes in metastatic tumor cells (bone marrow and liver combined) compared to primary tumor cells. The top upregulated gene was KCNK1 and the top downregulated genes were PDE7B and NEBL. Top upregulated pathways in the metastatic cells were involved in ion transport, cell signaling, and cell proliferation. Top downregulated pathways were involved in DNA synthesis, transcription, and cellular metabolism. CONCLUSIONS: In metastatic NB cells, our study identified the upregulation of biologic processes involved in cell cycle regulation, cell proliferation, migration, and invasion. Ongoing studies aim to validate downstream translation of these genomic alterations, as well as target these pathways to more effectively suppress and inhibit recurrent metastatic disease in NB.
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Regulação Neoplásica da Expressão Gênica , Camundongos Endogâmicos NOD , Camundongos SCID , Neuroblastoma , Animais , Neuroblastoma/patologia , Neuroblastoma/genética , Neuroblastoma/metabolismo , Humanos , Camundongos , Linhagem Celular Tumoral , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias da Medula Óssea/secundário , Neoplasias da Medula Óssea/genética , Perfilação da Expressão Gênica , TranscriptomaRESUMO
INTRODUCTION: Pediatric surgical care is becoming increasingly regionalized, often resulting in limited access. Interfacility transfers pose a significant financial and emotional burden to when they are potentially avoidable. Of transferred patients, we sought to identify clinical factors associated with avoidable transfers in pediatric patients with suspected appendicitis. METHODS: We performed a single-center retrospective study at an academic tertiary referral children's hospital in an urban setting. We included children who underwent interfacility transfer to our center with a transfer diagnosis of appendicitis from July 1, 2021 to June 30, 2023. Encounters were designated as either an appropriate transfer (underwent appendectomy) or an avoidable transfer (did not undergo appendectomy). Encounters treated nonoperatively for complicated appendicitis were excluded. Bivariate analysis was performed using Mann-Whitney test and chi-square tests. RESULTS: A total of 444 patients were included: 71.2% were classified as appropriate transfers and 28.8% as avoidable transfers. Patients with avoidable transfer were younger compared to those in the appropriate transfer cohort (median age 9 y, interquartile range: 7-13 versus 11 y, interquartile range: 8-14; P < 0.001). Avoidable transfers less frequently presented with the typical symptoms of fever, migratory abdominal pain, anorexia, and nausea/emesis (P = 0.005). Avoidable transfers also reported shorter symptom duration (P = 0.040) with lower median white blood cell count (P < 0.001), neutrophil percentage (P < 0.001), and C-reactive protein levels (P < 0.003). Avoidable transfers more frequently underwent repeat imaging upon arrival (42.9% versus 12.7%, P < 0.001). CONCLUSIONS: These findings highlight the importance of clinical history in children with suspected appendicitis. Younger patients without typical symptoms of appendicitis, those with a shorter duration of symptoms, and lower serum inflammatory markers may benefit from close observation without transfer.
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Apendicectomia , Apendicite , Transferência de Pacientes , Humanos , Apendicite/cirurgia , Apendicite/diagnóstico , Criança , Transferência de Pacientes/estatística & dados numéricos , Transferência de Pacientes/organização & administração , Estudos Retrospectivos , Masculino , Feminino , Adolescente , Apendicectomia/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Hospitais Pediátricos/organização & administração , Pré-EscolarRESUMO
PURPOSE: Pilonidal disease (PD) is marked by chronic inflammation and frequent recurrence which can decrease quality of life. However, debate remains regarding the optimal treatment for PD in the pediatric population. This study compares two recommended treatment approaches-excision with off-midline flap reconstruction (OMF: Bascom cleft lift flap, modified Limberg flap) and minimally invasive endoscopic pilonidal sinus treatment (EPSiT). METHODS: Single-center retrospective evaluation of patients 1-21 years of age with PD who underwent either excision with OMF reconstruction or EPSiT between 10/1/2011 and 10/31/2021. Outcomes included were disease recurrence, reoperation, and wound complication rates. Comparisons were performed using Chi-square and Mann-Whitney U tests. RESULTS: 18 patients underwent excision/OMF reconstruction and 45 patients underwent EPSiT. The excision/OMF reconstruction cohort was predominantly male (44.4% vs 17.8% p = 0.028), with history of prior pilonidal infection (33.3% vs 6.7%; p = 0.006), and longer median operative time (60 min vs 17 min; p < 0.001). The excision/OMF reconstruction cohort had a higher rate of wound complications (22.2% vs 0%; p = 0.001), but lower rates of disease recurrence (5.6% vs 33.3%; p = 0.022) and reoperation (5.6% vs 31.1%; p = 0.031). CONCLUSION: In pediatric patients with PD, excision with OMF reconstruction may decrease recurrence and reoperation rates with increased operative times and wound complication rates, compared to EPSiT.
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Seio Pilonidal , Dermatopatias , Humanos , Criança , Masculino , Feminino , Seio Pilonidal/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Endoscopia , ReoperaçãoRESUMO
INTRODUCTION: Counseling on the immediate postoperative experience for outpatient procedures is largely based on anecdotal experience. We devised a short messaging service (SMS) survey using mobile phone text messages to evaluate real-time patient recovery following outpatient thyroid or parathyroid surgery. MATERIALS AND METHODS: Daily automated SMS surveys were sent the evening of the operation until postoperative day 10. Pain, opioid use, voice quality, and energy levels were assessed. Impaired voice and energy was defined as a score < 2/3 of normal. RESULTS: One hundred fifty five patients were enrolled with an overall response rate of 81.6%. One hundred thirty three patients had an individual response rate > 50% and were included in the final analysis. Median patient age was 60 y with 102 females (76.7%). Seventy patients (52.6%) underwent parathyroidectomy and 66 (49.6%) thyroidectomy and 10 (7.5%) neck dissection. Forty eight patients (36.1%) did not use any opioids postoperatively. Independent risk factors for higher total pain scores included thyroidectomy and patients with preoperative opioid or tobacco use, while increased opioid use was associated with age < 60 y, body mass index > 30 kg/m2, preoperative opioid or tobacco use, and history of anxiety or depression. Patients with loss of intraoperative recurrent laryngeal nerve signaling had a significantly worse overall voice score (54.65 versus 92.67, P < 0.001). Up to 10% of patients were still using opioids and/or reported impaired voice and energy levels beyond 1 wk postoperatively. CONCLUSIONS: Real-time SMS survey is an effective and potentially valuable way to monitor patient recovery following surgery. A subset of patients reported impaired voice and energy and was still using opioids beyond 1 wk after thyroid and parathyroid surgery and these patients may benefit from closer follow-up and earlier intervention.
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Analgésicos Opioides , Glândula Tireoide , Feminino , Humanos , Tireoidectomia/efeitos adversos , Paratireoidectomia/efeitos adversos , Dor/etiologiaRESUMO
All organisms must simultaneously tolerate the environment and access limiting resources if they are to persist. Approaches to understanding abiotic filtering and competitive interactions have generally been developed independently. Consequently, integrating those factors to predict species abundances and community structure remains an unresolved challenge. We introduce a new synthetic framework that models both abiotic filtering and competition by using functional traits. First, our framework estimates species carrying capacities along abiotic gradients. Second, it estimates pairwise competitive interactions as a function of species trait differences. Applied to the study of a complex wetland community, our combined approach more than doubles the explained variance of species abundances compared to a model of abiotic tolerances alone. Trait-based integration of competitive interactions and abiotic filtering improves our ability to predict species abundances, bringing us closer to more accurate predictions of biodiversity structure in a changing world.
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Biodiversidade , Ecossistema , FenótipoRESUMO
PREMISE: Recent, rapid radiations present a challenge for phylogenetic reconstruction. Fast successive speciation events typically lead to low sequence divergence and poorly resolved relationships with standard phylogenetic markers. Target sequence capture of many independent nuclear loci has the potential to improve phylogenetic resolution for rapid radiations. METHODS: Here we applied target sequence capture with 353 protein-coding genes (Angiosperms353 bait kit) to Veronica sect. Hebe (common name hebe) to determine its utility for improving the phylogenetic resolution of rapid radiations. Veronica section Hebe originated 5-10 million years ago in New Zealand, forming a monophyletic radiation of ca 130 extant species. RESULTS: We obtained approximately 150 kbp of 353 protein-coding exons and an additional 200 kbp of flanking noncoding sequences for each of 77 hebe and two outgroup species. When comparing coding, noncoding, and combined data sets, we found that the latter provided the best overall phylogenetic resolution. While some deep nodes in the radiation remained unresolved, our phylogeny provided broad and often improved support for subclades identified by both morphology and standard markers in previous studies. Gene-tree discordance was nonetheless widespread, indicating that additional methods are needed to disentangle fully the history of the radiation. CONCLUSIONS: Phylogenomic target capture data sets both increase phylogenetic signal and deliver new insights into the complex evolutionary history of rapid radiations as compared with traditional markers. Improving methods to resolve remaining discordance among loci from target sequence capture is now important to facilitate the further study of rapid radiations.
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Veronica , Evolução Biológica , Núcleo Celular , Nova Zelândia , FilogeniaRESUMO
The role of whole-genome duplication (WGD) in facilitating shifts into novel biomes remains unknown. Focusing on two diverse woody plant groups in New Zealand, Coprosma (Rubiaceae) and Veronica (Plantaginaceae), we investigate how biome occupancy varies with ploidy level, and test the hypothesis that WGD increases the rate of biome shifting. Ploidy levels and biome occupancy (forest, open and alpine) were determined for indigenous species in both clades. The distribution of low-ploidy (Coprosma: 2x, Veronica: 6x) versus high-ploidy (Coprosma: 4-10x, Veronica: 12-18x) species across biomes was tested statistically. Estimation of the phylogenetic history of biome occupancy and WGD was performed using time-calibrated phylogenies and the R package BioGeoBEARS. Trait-dependent dispersal models were implemented to determine support for an increased rate of biome shifting among high-ploidy lineages. We find support for a greater than random portion of high-ploidy species occupying multiple biomes. We also find strong support for high-ploidy lineages showing a three- to eightfold increase in the rate of biome shifts. These results suggest that WGD promotes ecological expansion into new biomes.
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Plantaginaceae , Rubiaceae , Veronica , Ecossistema , Duplicação Gênica , Nova Zelândia , Filogenia , PoliploidiaRESUMO
Nuclear magnetic resonance (NMR) is potentially a very powerful process analytical technology (PAT) tool as it gives an atomic resolution picture of the reaction mixture without the need for chromatography. NMR is well suited for interrogating transient intermediates, providing kinetic information via NMR active nuclei, and most importantly provides universally quantitative information for all species in solution. This contrasts with commonly used PAT instruments, such as Raman or Flow-infrared (IR), which requires a separate calibration curve for every component of the reaction mixture. To date, the large footprint of high-field (≥400 MHz) NMR spectrometers and the immobility of superconducting magnets, coupled with strict requirements for the architecture for the room it is to be installed, have been a major obstacle to using this technology right next to fume hoods where chemists perform synthetic work. Here, we describe the use of a small, lightweight 60 MHz Benchtop NMR system (Nanalysis Pro-60) located on a mobile platform, that was used to monitor both small and intermediate scale Grignard formation and coupling reactions. We also show how low field NMR can provide a deceptively simple yes/no answer (for a system that would otherwise require laborious off-line testing) in the enrichment of one component versus another in a kilogram scale distillation. Benchtop NMR was also used to derive molecule specific information from Flow-IR, a technology found in most manufacturing sites, and compare the ease at which the concentrations of the reaction mixtures can be derived by NMR versus IR.
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Efforts to increase deceased donation have included the use of US Public Health Service (PHS) high-risk donors. The homeless have high rates of medical and substance abuse issues that are often unrecognized. This study investigates whether the homeless should become suitable organ donors. We retrospectively reviewed 193 brain-dead prospective donors from Hawaii's organ procurement organization (OPO; 2013-2018) and compared two groups: homeless (n = 13) and non-homeless (n = 180) prospective donors. The homeless prospective donors were older (48.0 vs 40.7 years, P = .009) and had more substance abuse (30.8% vs 10%, P = .046), methamphetamine use (53.8% vs 12.2%, P = .001), cocaine use (23.1% vs 3.9%, P = .022), and urine with amphetamines (54.5% vs 17.9%, P = .049). The homeless prospective donors trended toward more PHS high-risk designation (50% vs 19%, P = .062). There was no difference in medical history, gender/race, hepatitis serologies, authorization for donation, and organs procured/transplanted between prospective donors. We have provided evidence that the homeless should become prospective organ donors; however, they have more high-risk behaviors and often have limited information. Larger studies from OPOs are needed to better characterize organ donation and track disease transmission in this population.
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Morte Encefálica , Sobrevivência de Enxerto , Pessoas Mal Alojadas/estatística & dados numéricos , Transplante de Órgãos/estatística & dados numéricos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Forest community assembly is usually framed in terms of sporophyte dynamics; however, the recruitment and maintenance of fern populations, frequently influential in forest composition and structure, are initially determined by gametophytes. Sporophytes of three Cyathea tree fern species show habitat partitioning along gradients of phosphorus and light; we asked whether gametophyte niche differences parallel this pattern. To compare niche characteristics among taxa we compared growth rates to a size threshold (≥3 mm) of gametophytes under controlled conditions using a multi-factorial, multi-level (3 × 4) experiment, varying irradiance (5.4 ± 4.4; 59.1 ± 44.3; 107 ± 74.1 µmol m-2 s-1) and orthophosphate concentrations (5, 10, 20, 40 mg kg-1). Gametophytes of the pioneer species C. medullaris developed to the size threshold across a broad range of phosphate and irradiance treatments (more than 20% of gametophytes in ≥ 7 of the 12 treatments), peaking at 20 mg kg-1 P and 60 µmol m-2 s-1 irradiance. The growth rates of the forest understorey species C. dealbata and C. smithii also peaked at 60 µmol m-2 s-1 but varied across treatments, suggesting niche differentiation along irradiance and orthophosphate gradients. Our analysis suggests that gametophyte development is strategically aligned to the ecological habits of sporophytes and that forest community assembly is likely strongly influenced by the independent gametophyte life-stage.
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Gleiquênias , Células Germinativas Vegetais , Ecossistema , Florestas , ÁrvoresRESUMO
Abiotic filters have been found either to increase or reduce evolutionary relatedness in plant communities, making it difficult to generalize responses of this major feature of biodiversity to future environmental change. Here, we hypothesized that the responses of phylogenetic structure to environmental change ultimately depend on how species have evolved traits for tolerating the resulting abiotic changes. Working within ephemeral wetlands, we tested whether species were increasingly related as flooding duration intensified. We also identified the mechanisms underlying increased relatedness by measuring root aerenchyma volume (RAV), a trait which promotes waterlogging tolerance. We found that species-specific responses to flooding explained most of the variation in occurrence for 63 vascular plant species across 5170 plots. For a subset of 22 species, we attributed these responses to variation in RAV. Large RAV specifically increased occurrence when flooding lasted for longer time periods, because large RAV reduced above-ground biomass loss. As large RAV was evolutionarily conserved within obligate wetland species, communities were more phylogenetically related as flooding increased. Our study shows how reconstructing the evolutionary history of traits that influence the responses of species to environmental change can help to predict future patterns in phylogenetic structure.
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Inundações , Filogenia , Plantas/classificação , Adaptação Fisiológica , Raízes de Plantas/fisiologia , Porosidade , Probabilidade , Especificidade da EspécieRESUMO
Evolutionary priority effects, where early-arriving lineages occupy niche space via diversification and preclude dominance of later arrivals, have been observed in alpine and forest communities. However, the potential for evolutionary priority effects to persist in an era of rapid global change remains unclear. Here, we use a natural experiment of historical disturbance in New Zealand to test whether anthropogenic changes in available habitat and nonnative invasion eliminate the role of evolutionary priority effects in community assembly. We also test whether evolutionary priority effects diminish with decreasing resource availability. Older plant clades, as estimated by clade crown age, were relatively more abundant in both primary and secondary grassland. Relative abundance in primary grassland decreased with clade stem age, but only weakly. However, for both clade age estimates, relative abundance decreased with age when nonnative biomass was high and soil moisture was low. Our data show that patterns in community structure consistent with evolutionary priority effects can occur in both primary and secondary grasslands, the latter created by anthropogenic disturbance. However, nonnative invasion may overwhelm the effect of immigration timing on community dominance, possibly as a result of high immigration rates and preadaptation to anthropogenically modified environments.
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Evolução Biológica , Ecossistema , Plantas , Pradaria , Espécies Introduzidas , Modelos Biológicos , Nova Zelândia , Filogenia , Solo/químicaRESUMO
National scale initiatives are being attempted in New Zealand (NZ) to meet important environmental goals following land-use intensification over recent decades. Riparian restoration to filter agricultural spillover effects is currently the most widely practised mitigation measure but few studies have investigated the cumulative value of these practices at a national level. We use an applied economic land use model the benefits (GHG emissions, N leaching, P loss, sedimentation and biodiversity gain) and relevant costs (fencing, alternative stock water supplies, restoration planting and opportunity costs) of restoring riparian margins (5-50 m) on all streams in NZ flowing through current primary sector land. Extensive sensitivity analysis reveals that depending on margin width and cost assumptions, riparian margin restoration generates net benefits of between NZ$1.7 billion - $5.2 billion/yr and benefit-cost ratios ranging between 1.4 and 22.4. This suggests that even when not monetising the increase in biodiversity or components of stream ecosystem health and other benefits from planting riparian strips, the benefits to climate and freshwater are significantly greater than the implementation costs of riparian restoration.
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Conservação dos Recursos Naturais/economia , Recuperação e Remediação Ambiental/economia , Modelos Econômicos , Agricultura , Biodiversidade , Clima , Ecossistema , Água Doce , Efeito Estufa , Nova Zelândia , Plantas , Rios , Abastecimento de ÁguaRESUMO
Plant radiations are widespread but their influence on community assembly has rarely been investigated. Theory and some evidence suggest that radiations can allow lineages to monopolize niche space when founding species arrive early into new bioclimatic regions and exploit ecological opportunities. These early radiations may subsequently reduce niche availability and dampen diversification of later arrivals. We tested this hypothesis of time-dependent lineage diversification and community dominance using the alpine flora of New Zealand. We estimated ages of 16 genera from published phylogenies and determined their relative occurrence across climatic and physical gradients in the alpine zone. We used these data to reconstruct occupancy of environmental space through time, integrating palaeoclimatic and palaeogeological changes. Our analysis suggested that earlier-colonizing lineages encountered a greater availability of environmental space, which promoted greater species diversity and occupancy of niche space. Genera that occupied broader niches were subsequently more dominant in local communities. An earlier time of arrival also contributed to greater diversity independently of its influence in accessing niche space. We suggest that plant radiations influence community assembly when they arise early in the occupancy of environmental space, allowing them to exclude later-arriving colonists from ecological communities by niche preemption.
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Adaptação Fisiológica , Biodiversidade , Evolução Biológica , Filogenia , Plantas/genética , Biota , Ecologia , EcossistemaRESUMO
Alternative stable states have long been thought to exist in natural communities, but direct evidence for their presence and for the environmental switches that cause them has been scarce. Using a combination of greenhouse and field experiments, we investigated the environmental drivers associated with two distinctive herbaceous communities in coastal ecosystems in New Zealand. In a mosaic unrelated to micro-topography, a community dominated largely by native turf species (notably Leptinella dioica, Samolus repens, and Selliera radicans) alternates with vegetation comprising exotic (i.e., nonnative) pasture species (notably Agrostis stolonifera, Holcus lanatus, Lolium perenne, and Trifolium repens). The species of these two communities differ in functional characters related to leaf longevity and growth rate, and occupy soils of differing nitrogen levels. Both spatial and environmental factors influenced the species composition locally. Reciprocal transplants of soil, with and without associated vegetation, showed that a native turf community developed when sward or soil from either community was bounded by turf, and a pasture community developed when sward or soil from either community was surrounded by pasture. In artificial mixed communities in the greenhouse, turf was able to invade the pasture community where the vegetation was clipped to simulate grazing, and also where Trifolium was removed and/or salt spray was applied. The pasture community invaded the turf where Trifolium was present or nitrogen was added. These results were supported by trends in experimentally manipulated field plots, where the amount of turf cover increased when nitrogen was kept low and when salt spray was applied, whereas pasture cover increased in the absence of salt spray. Thus, persistence of the native turf community is dependent on grazing, both directly and via its effect on keeping nitrogen levels low by excluding the exotic, nitrogen-fixing Trifolium, and by exposing the vegetation to salt spray. If any of these factors change, there could be a state change to pasture dominance that might be resistant to reversion to turf. Managing such coastal herbaceous communities therefore requires an understanding of the environmental and species characteristics that maintain alternative states.
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Ecossistema , Poaceae/efeitos dos fármacos , Poaceae/fisiologia , Água do Mar , Demografia , Nova Zelândia , Nitrogênio/química , Nitrogênio/metabolismo , Cloreto de Sódio/farmacologia , Solo/químicaRESUMO
The temporal stability of plant reproductive features on islands has rarely been tested. Using flowers, fruits/cones and seeds from a well-dated (23 Ma) Miocene Lagerstätte in New Zealand, we show that across 23 families and 30 genera of forest angiosperms and conifers, reproductive features have remained constant for more than 20 Myr. Insect-, wind- and bird-pollinated flowers and wind- and bird-dispersed diaspores all indicate remarkable reproductive niche conservatism, despite widespread environmental and biotic change. In the past 10 Myr, declining temperatures and the absence of low-latitude refugia caused regional extinction of thermophiles, while orogenic processes steepened temperature, precipitation and nutrient gradients, limiting forest niches. Despite these changes, the palaeontological record provides empirical support for evidence from phylogeographical studies of strong niche conservatism within lineages and biomes.
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Evolução Biológica , Magnoliopsida , Polinização/fisiologia , Traqueófitas , Clima , Florestas , Fósseis , Nova Zelândia , Filogenia , Filogeografia , Reprodução , Fatores de TempoRESUMO
Pediatric precision oncology has provided a greater understanding of the wide range of molecular alterations in difficult-to-treat or rare tumors with the aims of increasing survival as well as decreasing toxicity and morbidity from current cytotoxic therapies. In this article, the authors discuss the current state of pediatric precision oncology which has increased access to novel targeted therapies while also providing a framework for clinical implementation in this unique population. The authors evaluate the targetable mutations currently under investigation-with a focus on pediatric solid tumors-and discuss the key surgical implications associated with novel targeted therapies.
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Antineoplásicos , Neoplasias , Criança , Humanos , Neoplasias/genética , Neoplasias/cirurgia , Neoplasias/tratamento farmacológico , Medicina de Precisão , Oncologia , Antineoplásicos/uso terapêutico , Mutação , Terapia de Alvo MolecularRESUMO
BACKGROUND: Gastrostomy creation is a common pediatric surgical procedure, but the time to initiation of feeds and to goal feeding volumes postoperatively varies greatly. Delays in reaching goal feeding volumes promote malnutrition and may prolong hospital length of stay. We hypothesized that implementing an accelerated, standardized post-gastrostomy feeding protocol would allow patients to reach goal feeding volumes sooner, without increasing postoperative complications. METHODS: We conducted a retrospective cohort study of children who underwent gastrostomy tube placement between 1/1/2022 and 11/30/2023. The feeding protocol was implemented on 11/16/2022, with patients separated into pre- and post-protocol cohorts. Abstracted data included comorbidities, time to initiation of enteral feeds, time to goal feeding volume, and postoperative complications. RESULTS: 322 patients were included: 166 pre-protocol and 156 post-protocol. The post-protocol cohort had a greater proportion of patients with gastrointestinal and/or cardiac comorbidities (P < .001). Through the protocol, postoperative enteral feeds were initiated significantly faster (5.4 hrs [IQR 43-7.7] vs 7.0 hrs [IQR 5.6-14.3]; P < .001). The post-protocol cohort also achieved goal feeding volumes sooner (12.8 hrs [IQR 9.1-25.3] vs 26.3 hrs [IQR 21.6-38.9]; P < .001). Postoperative complication rates did not differ between cohorts. Sub-analysis of children with complex cardiac conditions also demonstrated faster time to goal nutrition without an associated increase in postoperative events. DISCUSSION: These findings demonstrate that our accelerated post-gastrostomy feeding protocol was effective in achieving goal enteral nutrition earlier without increasing postoperative adverse outcomes. This protocol may be used by other centers to safely expedite time to goal enteral feeds in children postoperatively.
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INTRODUCTION: Delayed primary repair of esophageal atresia in patients with high-risk physiologic and anatomic comorbidities remains a daunting challenge with an increased risk for peri-operative morbidity and mortality via conventional repair. The Connect-EA device facilitates the endoscopic creation of a secure esophageal anastomosis. This follow-up study reports our long-term outcomes with the novel esophageal magnetic compression anastomosis (EMCA) Connect-EA device for EA repair, as well as lessons learned from the ten first-in-human cases. We propose an algorithm to maximize the advantages of the device for EA repair. METHODS: Under compassionate use approval, from June 2019 to December 2022, ten patients with prohibitive surgical or medical risk factors underwent attempted EMCA with this device. All patients underwent prior gastrostomy, tracheoesophageal fistula ligation (if necessary), and demonstrated pouch apposition prior to EMCA. RESULTS: Successful device deployment and EMCA formation were achieved in nine patients (90%). Mean time to anastomosis formation was 8 days (range 5-14) and the device was retrieved endoscopically in five (56%) cases. At median follow-up of 22 months (range 4-45), seven patients (78%) are tolerating oral nutrition. Balloon dilations (median 4, range 1-11) were performed either prophylactically for radiographic asymptomatic anastomotic narrowing (n = 7, 78%) or to treat clinically-significant anastomotic narrowing (n = 2, 22%) with no ongoing dilations at 3-month follow up post-repair. CONCLUSION: EMCA with the Connect-EA device is a safe and feasible minimally-invasive alterative for EA repair in high-risk surgical patients. Promising post-operative outcomes warrant further Phase I investigation. LEVEL OF EVIDENCE: IV, Case series of novel operative technique without comparison group.
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Acetatos , Atresia Esofágica , Fístula Traqueoesofágica , Humanos , Atresia Esofágica/cirurgia , Ensaios de Uso Compassivo , Seguimentos , Anastomose Cirúrgica/métodos , Resultado do Tratamento , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: Surgical resection is a mainstay of treatment in high-risk neuroblastoma (HR-NB), but there exists wide variability in perioperative management practices. The aim of this study was to evaluate two standardized adult perioperative enhanced recovery practices (ERPs) in pediatric patients undergoing open resection of abdominal HR-NB. METHODS: All patients with abdominal HR-NB surgically resected at a free-standing children's hospital between 12/2010 and 7/2020 were retrospectively reviewed. Perioperative ERPs of interest included avoidance of routine nasogastric tube (NGT) use and the use of neuraxial anesthesia. Primary outcomes included time to enteral intake, urinary catheter use, opioid utilization, and length of stay (LOS). RESULTS: Overall, 37 children, median age 33 months (IQR: 20-48 months), were identified. Avoidance of an NGT allowed for earlier feeding after surgery (P = .03). Neuraxial anesthesia use more frequently required an indwelling urinary catheter (P < .01) for a longer duration (P = .02), with no difference in total opioid utilization (P = .77) compared to patients without neuraxial anesthesia. Postoperative LOS was unaffected by avoidance of routine NGT use (P = .68) or use of neuraxial anesthesia (P = .89). CONCLUSION: Children undergoing open resection of abdominal HR-NB initiated diet sooner when an NGT was not left postoperatively, and the need for a urinary catheter was significantly higher in patients who received neuraxial anesthesia. However, these two ERP components did not decrease postoperative LOS. To optimize the postoperative management of NB patients, postoperative NGTs should be avoided, while the benefit of neuraxial anesthesia is less clear as it necessitates the placement of a urinary catheter without decreasing opioid utilization.