RESUMEN
OBJECTIVE: Chat generative pre-trained transformer (ChatGPT) has garnered attention in health care for its potential to reshape patient interactions. As patients increasingly rely on artificial intelligence platforms, concerns about information accuracy arise. In-toeing, a common lower extremity variation, often leads to pediatric orthopaedic referrals despite observation being the primary treatment. Our study aims to assess ChatGPT's responses to pediatric in-toeing questions, contributing to discussions on health care innovation and technology in patient education. METHODS: We compiled a list of 34 common in-toeing questions from the "Frequently Asked Questions" sections of 9 health care-affiliated websites, identifying 25 as the most encountered. On January 17, 2024, we queried ChatGPT 3.5 in separate sessions and recorded the responses. These 25 questions were posed again on January 21, 2024, to assess its reproducibility. Two pediatric orthopaedic surgeons evaluated responses using a scale of "excellent (no clarification)" to "unsatisfactory (substantial clarification)." Average ratings were used when evaluators' grades were within one level of each other. In discordant cases, the senior author provided a decisive rating. RESULTS: We found 46% of ChatGPT responses were "excellent" and 44% "satisfactory (minimal clarification)." In addition, 8% of cases were "satisfactory (moderate clarification)" and 2% were "unsatisfactory." Questions had appropriate readability, with an average Flesch-Kincaid Grade Level of 4.9 (±2.1). However, ChatGPT's responses were at a collegiate level, averaging 12.7 (±1.4). No significant differences in ratings were observed between question topics. Furthermore, ChatGPT exhibited moderate consistency after repeated queries, evidenced by a Spearman rho coefficient of 0.55 ( P = 0.005). The chatbot appropriately described in-toeing as normal or spontaneously resolving in 62% of responses and consistently recommended evaluation by a health care provider in 100%. CONCLUSION: The chatbot presented a serviceable, though not perfect, representation of the diagnosis and management of pediatric in-toeing while demonstrating a moderate level of reproducibility in its responses. ChatGPT's utility could be enhanced by improving readability and consistency and incorporating evidence-based guidelines. LEVEL OF EVIDENCE: Level IV-diagnostic.
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Educación del Paciente como Asunto , Humanos , Niño , Reproducibilidad de los Resultados , Educación del Paciente como Asunto/métodos , Inteligencia Artificial , Pediatría/métodosRESUMEN
Dual-energy X-ray absorptiometry (DEXA) is the gold standard for osteoporosis screening and diagnosis. However, abdominal conventional computed tomography (CT) scan is widely available and multiple studies validated its use as a screening tool for osteoporosis compared to DEXA. The aim of this study was to determine the reliability of measuring core muscle size at the L3-L4 intervertebral disk space and estimate the relationship between core muscle size and bone mineral density (BMD) measured by DEXA. Retrospective chart review was performed on patients who underwent a DEXA scan for osteoporosis and a conventional abdominal CT scan within one-year apart. Total cross-sectional area (CSA) and Hounsfield Unit (HU) density of core muscles (psoas, paraspinal, and abdominal wall muscles) were measured. The association between psoas, paraspinal, abdominal, and central muscle CSA and Bone Mineral density (BMD) at L3, L4, total Lumbar Spine (LS), and right (R) and left (L) hip was estimated in crude and adjusted for age and sex linear regression models. Sixty patients (37 females, 23 males) met the inclusion criteria. The average interval between DEXA and abdominal CT scans was 3.6 months (range 0.1-10.2). Psoas muscle density was significantly positively associated with R hip BMD in both crude and adjusted models (ßâ¯=â¯20.2, pâ¯=â¯0.03; ßâ¯=â¯18.5, pâ¯=â¯0.01). We found a significant positive linear association between psoas muscle CSA and HU density with BMD of LS, R, and L hip in both crude and adjusted models. The strongest significant positive linear association was observed between total abdominal CSA and R hip BMD in crude and age and sex adjusted (ßâ¯=â¯85.3, pâ¯=â¯0.01; ßâ¯=â¯63.9, pâ¯=â¯0.02, respectively). CT scans obtained for various clinical indications can provide valuable information regarding BMD. This is the first study investigating association between BMD with central muscle density and CSA, and it demonstrated their significant positive the association.
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Densidad Ósea , Osteoporosis , Masculino , Femenino , Humanos , Densidad Ósea/fisiología , Absorciometría de Fotón/métodos , Estudios Retrospectivos , Reproducibilidad de los Resultados , Osteoporosis/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Vértebras Lumbares/diagnóstico por imagenRESUMEN
BACKGROUND: Complement represents a crucial mediator of neuroinflammation and neurodegeneration after traumatic brain injury. The role of the terminal complement activation pathway, leading to generation of the membrane attack complex (MAC), has not been thoroughly investigated. CD59 is the major regulator of MAC formation and represents an essential protector from homologous cell injury after complement activation in the injured brain. METHODS: Mice deleted in the Cd59a gene (CD59a-/-) and wild-type littermates (n = 60) were subjected to focal closed head injury. Sham-operated (n = 60) and normal untreated mice (n = 14) served as negative controls. The posttraumatic neurological impairment was assessed for up to one week after trauma, using a standardized Neurological Severity Score (NSS). The extent of neuronal cell death was determined by serum levels of neuron-specific enolase (NSE) and by staining of brain tissue sections in TUNEL technique. The expression profiles of pro-apoptotic (Fas, FasL, Bax) and anti-apoptotic (Bcl-2) mediators were determined at the gene and protein level by real-time RT-PCR and Western blot, respectively. RESULTS: Clinically, the brain-injured CD59a-/- mice showed a significantly impaired neurological outcome within 7 days, as determined by a higher NSS, compared to wild-type controls. The NSE serum levels, an indirect marker of neuronal cell death, were significantly elevated in CD59a-/- mice at 4 h and 24 h after trauma, compared to wild-type littermates. At the tissue level, increased neuronal cell death and brain tissue destruction was detected by TUNEL histochemistry in CD59a-/- mice within 24 hours to 7 days after head trauma. The analysis of brain homogenates for potential mediators and regulators of cell death other than the complement MAC (Fas, FasL, Bax, Bcl-2) revealed no difference in gene expression and protein levels between CD59a-/- and wild-type mice. CONCLUSION: These data emphasize an important role of CD59 in mediating protection from secondary neuronal cell death and further underscore the key role of the terminal complement pathway in the pathophysiology of traumatic brain injury. The exact mechanisms of complement MAC-induced secondary neuronal cell death after head injury require further investigation.
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Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Encéfalo/metabolismo , Encéfalo/patología , Antígenos CD59/metabolismo , Animales , Apoptosis , Antígenos CD59/genética , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Enfermedades Desmielinizantes/patología , Modelos Animales de Enfermedad , Proteína Ligando Fas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/metabolismo , Neuronas/patología , Fosfopiruvato Hidratasa/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Mensajero/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Receptor fas/metabolismoRESUMEN
Severe burn injury remains a major burden on patients and healthcare systems. Following severe burns, the injured tissues mount a local inflammatory response aiming to restore homeostasis. With excessive burn load, the immune response becomes disproportionate and patients may develop an overshooting systemic inflammatory response, compromising multiple physiological barriers in the lung, kidney, liver, and brain. If the blood-brain barrier is breached, systemic inflammatory molecules and phagocytes readily enter the brain and activate sessile cells of the central nervous system. Copious amounts of reactive oxygen species, reactive nitrogen species, proteases, cytokines/chemokines, and complement proteins are being released by these inflammatory cells, resulting in additional neuronal damage and life-threatening cerebral edema. Despite the correlation between cerebral complications in severe burn victims with mortality, burn-induced neuroinflammation continues to fly under the radar as an underestimated entity in the critically ill burn patient. In this paper, we illustrate the molecular events leading to blood-brain barrier breakdown, with a focus on the subsequent neuroinflammatory changes leading to cerebral edema in patients with severe burns.
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Barrera Hematoencefálica/fisiopatología , Edema Encefálico/etiología , Edema Encefálico/fisiopatología , Quemaduras/complicaciones , Encefalitis/etiología , Encefalitis/fisiopatología , Biomarcadores/metabolismo , Barrera Hematoencefálica/inmunología , Edema Encefálico/inmunología , Edema Encefálico/psicología , Quemaduras/inmunología , Encefalitis/inmunología , Encefalitis/psicología , HumanosRESUMEN
INTRODUCTION: Septic encephalopathy secondary to a breakdown of the blood-brain barrier (BBB) is a known complication of sepsis. However, its pathophysiology remains unclear. The present study investigated the effect of complement C5a blockade in preventing BBB damage and pituitary dysfunction during experimental sepsis. METHODS: Using the standardised caecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with either neutralising anti-C5a antibody or pre-immune immunoglobulin (Ig) G as a placebo. Sham-operated animals served as internal controls. RESULTS: Placebo-treated septic rats showed severe BBB dysfunction within 24 hours, accompanied by a significant upregulation of pituitary C5a receptor and pro-inflammatory cytokine expression, although gene levels of growth hormone were significantly attenuated. The pathophysiological changes in placebo-treated septic rats were restored by administration of neutralising anti-C5a antibody to the normal levels of BBB and pituitary function seen in the sham-operated group. CONCLUSIONS: Collectively, the neutralisation of C5a greatly ameliorated pathophysiological changes associated with septic encephalopathy, implying a further rationale for the concept of pharmacological C5a inhibition in sepsis.
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Barrera Hematoencefálica/metabolismo , Complemento C5a/antagonistas & inhibidores , Complemento C5a/inmunología , Enfermedades de la Hipófisis/metabolismo , Enfermedades de la Hipófisis/prevención & control , Sepsis/metabolismo , Animales , Barrera Hematoencefálica/efectos de los fármacos , Inmunoglobulina G/farmacología , Inmunoglobulina G/uso terapéutico , Masculino , Enfermedades de la Hipófisis/fisiopatología , Ratas , Ratas Sprague-Dawley , Receptor de Anafilatoxina C5a/antagonistas & inhibidores , Receptor de Anafilatoxina C5a/biosíntesis , Sepsis/complicaciones , Sepsis/tratamiento farmacológicoRESUMEN
OBJECTIVES: To investigate the association between lean psoas cross-sectional area (CSA) and 1-year all-cause mortality in elderly patients sustaining pelvic and long bone fractures. DESIGN: Retrospective cohort. SETTING: Level I trauma center. PATIENTS: Elderly trauma patients admitted from 2007 to 2014. METHODS: We reviewed demographic and clinical data, injury mechanism, fracture OTA/AO classification, and mortality. Axial computed tomography images were used to measure lean psoas CSA at the L3-L4 disk space. Cox proportional hazard regression analysis was used to estimate 1-year mortality association with psoas CSA in crude and adjusted for age, body mass index, Injury Severity Score, medical comorbidities, and discharge destination in total population and stratified by sex. MAIN OUTCOME MEASUREMENT: One-year all-cause mortality defined as death within 12 months from date of hospitalization. RESULTS: Five hundred fifty-eight patients (54% female, 46% male) were analyzed. The pelvis was most commonly fractured (37.81%). A statistically significant association was observed between decreased lean psoas CSA and 1-year mortality in total population {hazard ratio [HR] = 0.93 [95% confidence interval (CI) = 0.90-0.96], P < 0.0001}. Stratification by gender revealed a statistically significant mortality HR in male patients [HR = 0.89 (95% CI = 0.84-0.96), P = 0.002]. We did not find a statistically significant mortality HR in female patients [HR = 0.95 (95% CI = 0.89-1.01), P = 0.103]. CONCLUSIONS: In this cohort of elderly orthopaedic trauma patients, decreased lean psoas CSA was associated with increased 1-year all-cause mortality in total population and males. Further investigation of the association of sarcopenia with mortality in the elderly is warranted. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Fracturas Óseas/complicaciones , Fracturas Óseas/mortalidad , Huesos Pélvicos/lesiones , Músculos Psoas/patología , Sarcopenia/complicaciones , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Hospitalización , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Sarcopenia/mortalidad , Factores Sexuales , Tasa de SupervivenciaRESUMEN
The Notch signaling pathway has been shown to be upregulated in colorectal cancer (CRC) and important for the self-renewal of cancer stem cells. In this study, we evaluated the efficacy of PF-03084014, a γ-secretase inhibitor, in combination with irinotecan to identify the effects of treatment on tumor recurrence and the tumor-initiating population in our CRC preclinical explant model. The combination of PF-03084014 and irinotecan had the greatest effect at reducing tumor growth on four CRC tumors when compared with treatment with PF-03084014 or irinotecan alone. The combination significantly reduced tumor recurrence in two CRC explants (CRC001 and CRC036) after treatment was discontinued. Both of these tumors exhibited elevated baseline levels of Notch pathway activation as well as an increase in NOTCH1 gene copy number when compared with the two CRC explants (CRC026 and CRC027) where tumors reappeared quickly after termination of treatment. Isolation and injection of aldehyde dehydrogenase (ALDH(+) and ALDH(-)) cells in an in vivo explant model demonstrated that the ALDH(+) cell population were tumorigenic. Evaluation of the ALDH(+) cells after 28 days of treatment showed that the combination reduced the ALDH(+) population in the tumors that did not regrow. Furthermore, ALDH(+) cells from CRC001 and CRC027 were injected in vivo and treated immediately for 28 days. Two months after treatment, tumors were evident in the combination treatment group for CRC027 but not for CRC036. These results indicate the combination of PF-03084014 and irinotecan may be effective in reducing tumor recurrence in CRC patients whose tumors exhibit elevated levels of the Notch pathway.
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Aldehído Deshidrogenasa/metabolismo , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Receptor Notch1/metabolismo , Aldehído Deshidrogenasa/genética , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Animales , Camptotecina/farmacología , Camptotecina/uso terapéutico , Neoplasias Colorrectales/genética , Femenino , Dosificación de Gen/genética , Humanos , Hibridación Fluorescente in Situ , Irinotecán , Ratones , Ratones Desnudos , Receptor Notch1/genética , Transducción de Señal , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
PURPOSE: Dysregulation of the phosphoinositide 3-kinase (PI3K) and Src signaling pathways commonly occur in colorectal cancer. Mutations in the PIK3CA gene are associated with an increase in severity of disease and worse clinical outcomes. Elevated levels of Src have been identified in premalignant lesions and are suggested to play a central role in tumor progression. Because these pathways appear to enhance tumor growth and metastasis, molecularly targeted agents for both pathways are currently being evaluated in early-phase clinical trials. EXPERIMENTAL DESIGN: We used colorectal cancer cell lines and a patient-derived explant model to investigate the efficacy of saracatinib. Mutations in the PIK3CA were evaluated to examine the association between mutations in the PIK3CA gene and sensitivity to saracatinib. RESULTS: We have identified a subset of patients with a PIK3CA (exon 9 and 20) mutation with increased sensitivity to saracatinib. A novel 3' untranslated region (UTR) mutation was also shown to be associated with increased sensitivity to saracatinib and have a reduced affinity for miR-520a and miR-525a. Importantly, we show that Src inhibition reduces the interaction between Src and p85, subsequently decreasing Akt-dependent signaling. CONCLUSION: These results indicate that a personalized approach in targeting Src in PIK3CA-mutant patients with colorectal cancers may prove effective in a subset of patients with this genetic alteration.
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Regiones no Traducidas 3'/genética , Benzodioxoles/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Resistencia a Antineoplásicos/genética , Mutación/genética , Fosfatidilinositol 3-Quinasas/genética , Quinazolinas/farmacología , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasa Clase I , Neoplasias Colorrectales/patología , Dosificación de Gen , Perfilación de la Expresión Génica , Humanos , Immunoblotting , Inmunoprecipitación , Ratones , MicroARNs/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosfohidrolasa PTEN , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Familia-src Quinasas/antagonistas & inhibidores , Familia-src Quinasas/genética , Familia-src Quinasas/metabolismoRESUMEN
PURPOSE: To evaluate the efficacy of saracatinib (AZD0530), an oral Src inhibitor, in colorectal cancer (CRC) and to identify biomarkers that predict antitumor activity. EXPERIMENTAL DESIGN: Twenty-three CRC cell lines were exposed to saracatinib, and baseline gene expression profiles of three sensitive and eight resistant cell lines in vitro and in vivo were used to predict saracatinib sensitivity in an independent group of 10 human CRC explant tumors using the gene array K-Top Scoring Pairs (K-TSP) method. In addition, fluorescence in situ hybridization (FISH) and immunoblotting determined both Src gene copy number and activation of Src, respectively. RESULTS: Two of 10 explant tumors were determined to be sensitive to saracatinib. The K-TSP classifier (TOX>GLIS2, TSPAN7>BCAS4, and PARD6G>NXN) achieved 70% (7 of 10) accuracy on the test set. Evaluation of Src gene copy number by FISH showed a trend toward significance (P = 0.066) with respect to an increase in Src gene copy and resistance to saracatinib. Tumors sensitive to saracatinib showed an increase in the activation of Src and FAK when compared with resistant tumors. CONCLUSIONS: Saracatinib significantly decreased tumor growth in a subset of CRC cell lines and explants. A K-TSP classifier (TOX>GLIS2, TSPAN7>BCAS4, and PARD6G>NXN) was predictive for sensitivity to saracatinib. In addition, increased activation of the Src pathway was associated with sensitivity to saracatinib. These results suggest that FISH, a K-TSP classifier, and activation of the Src pathway have potential in identifying CRC patients that would potentially benefit from treatment with saracatinib.