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1.
Geriatr Orthop Surg Rehabil ; 15: 21514593241280926, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39372372

RESUMEN

Introduction: We aimed to describe patient awareness regarding fall prevention and education, perceived causes of falls, and changes in attitude after experiencing a fall through interviews with older Korean patients who experienced falls with resultant hip fractures. Materials and Methods: We conducted face-to-face semi-structured in-depth interviews with 11 patients who were admitted to Kangbuk Samsung Hospital for hip fractures caused by falls and were referred to the Department of Rehabilitation Medicine for postsurgical rehabilitation between June 2022 and June 2023. The data were analyzed using the phenomenological method developed by Colaizzi. Results: Before hip fracture, none of the patients had received fall prevention education or perceived its necessity; however, they recognized its necessity retrospectively. Participants described the causes of falls as carelessness, actions taken at the time of the fall, environmental factors, and decreased physical function. Most participants believed that falls could be prevented through personal caution and activity restrictions. Some mentioned fall prevention education, exercise, wearing appropriate shoes, environmental adjustments, and seeking assistance from others as methods of preventing future falls. Most patients reported adopting a safety-seeking attitude after experiencing hip fracture. Many patients had negative thoughts such as guilt or thoughts of death, whereas only a few reported increased interest in education and exercise. Conclusions: We observed a lack of fall prevention education, misunderstanding regarding the cause of falls, and negative psychological changes after experiencing hip fractures due to falls in older Korean individuals. Recognizing and managing patient perceptions is crucial for effective fall prevention, requiring both healthcare provider awareness and active participation from patients and caregivers.

2.
BMB Rep ; 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39384178

RESUMEN

Cereblon (CRBN) is an extensively expressed protein involved in crucial physiological processes. This study reveals CRBN's role in governing hepatic fibroblast growth factor 23 (FGF23) expression and production via the cyclic adenosine monophosphate (cAMP) pathway in diabetic conditions. The expression of hepatic Crbn, Yin Yang 1 (Yy1), and Fgf23 genes were significantly increased in diabetic mice and forskolin (FSK)-treated primary hepatocytes, correlating with elevated FGF23 production. Overexpression of Crbn and Yy1 increased hepatic FGF23 and cytokines by upregulating YY1 gene expression, which was reduced in Crbn- and Yy1-silenced mice and primary hepatocytes. Besides, we found that CRBN-mediated regulation of hepatic FGF23 involved YY1 recruitment to the Fgf23 gene promoters, evidenced by reporter assays, deletion studies, and mutant analyses. These findings identify CRBN and YY1 as key contributors to gluconeogenic signaling-driven FGF23 production and inflammation in diabetes, highlighting their potential as therapeutic targets for addressing metabolic disorders like diabetes.

3.
Cartilage ; : 19476035241280072, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39311645

RESUMEN

Osteochondral lesions of the talus (OLT) involve the subchondral bone and the overlying articular cartilage. Various surgical treatments for these lesions are available, such as bone marrow stimulation (BMS), autologous osteochondral grafting, and fixation of an osteochondral fragment. Treatment choice depends on the condition of the lesion, which includes lesion size, morphology, location, and the presence of cysts. Among the surgical procedures available to date, in situ fixation of the osteochondral fragment has the advantage of restoring the articular surface while preserving the native hyaline cartilage and its subchondral bone. Fixation for OLT has been shown to be clinically successful for the treatment of both acute and chronic lesions. Moreover, the indication for osteochondral fragment fixation is expanding as recent studies have found good clinical outcomes in relatively small-sized lesions. The present article describes the current evidence on fixation for acute and chronic OLT.

4.
Acta Derm Venereol ; 104: adv40110, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39295582

RESUMEN

Population-based epidemiological studies on disease burden and risk factors for psoriatic arthritis (PsA) in patients with psoriasis (PsO) are limited, especially in Asian populations. Therefore, the aim was to determine the prevalence and incidence of PsA among PsO patients in Korea, and examine associated clinical factors. A cohort study was performed to determine the annual prevalence and incidence of PsA among PsO patients between 2008 and 2020 using nationwide claims data in Korea. Risk factors for PsA development were also examined using logistic regression among matched PsA cases and controls. An increasing trend in PsA prevalence per 1,000 patients was observed; prevalence was 6.17 (95% confidence interval [CI] 5.73-6.65) in 2008 and 19.03 (95% CI 18.39-19.70) in 2020. Similarly, the PsA incidence rate per 1,000 patient-years increased from 3.35 (95% CI 3.01-3.72) in 2008 to 5.01 (95% CI 4.68-5.36) in 2020. Patients with plaque PsO, moderate-to severe PsO, receiving oral systemic therapy or phototherapy, with a higher burden of comorbidities, and concomitant autoimmune diseases had a higher risk of PsA. The results provide insight into the burden of PsA among PsO patients in Korea and risk factors associated with developing PsA.


Asunto(s)
Artritis Psoriásica , Bases de Datos Factuales , Psoriasis , Humanos , Artritis Psoriásica/epidemiología , Artritis Psoriásica/diagnóstico , República de Corea/epidemiología , Masculino , Femenino , Incidencia , Prevalencia , Factores de Riesgo , Persona de Mediana Edad , Psoriasis/epidemiología , Psoriasis/diagnóstico , Adulto , Anciano , Comorbilidad , Adulto Joven , Factores de Tiempo , Medición de Riesgo , Índice de Severidad de la Enfermedad
5.
Biomolecules ; 14(9)2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39334923

RESUMEN

Mechanosensitive ion channels, particularly Piezo channels, are widely expressed in various tissues. However, their role in immune cells remains underexplored. Therefore, this study aimed to investigate the functional role of Piezo1 in the human eosinophil cell line AML14.3D10. We detected Piezo1 mRNA expression, but not Piezo2 expression, in these cells, confirming the presence of the Piezo1 protein. Activation of Piezo1 with Yoda1, its specific agonist, resulted in a significant calcium influx, which was inhibited by the Piezo1-specific inhibitor Dooku1, as well as other nonspecific inhibitors (Ruthenium Red, Gd3+, and GsMTx-4). Further analysis revealed that Piezo1 activation modulated the expression and secretion of both pro-inflammatory and anti-inflammatory cytokines in AML14.3D10 cells. Notably, supernatants from Piezo1-activated AML14.3D10 cells enhanced capsaicin and ATP-induced calcium responses in the dorsal root ganglion neurons of mice. These findings elucidate the physiological role of Piezo1 in AML14.3D10 cells and suggest that factors secreted by these cells can modulate the activity of transient receptor potential 1 (TRPV1) and purinergic receptors, which are associated with pain and itch signaling. The results of this study significantly advance our understanding of the function of Piezo1 channels in the immune and sensory nervous systems.


Asunto(s)
Eosinófilos , Canales Iónicos , Humanos , Canales Iónicos/metabolismo , Canales Iónicos/genética , Animales , Eosinófilos/metabolismo , Eosinófilos/inmunología , Ratones , Línea Celular , Calcio/metabolismo , Ganglios Espinales/metabolismo , Ganglios Espinales/citología , Citocinas/metabolismo , Rojo de Rutenio/farmacología , Adenosina Trifosfato/metabolismo , Tiadiazoles/farmacología , Pirazinas
6.
Diagnostics (Basel) ; 14(17)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39272681

RESUMEN

Since the early 2000s, minimally invasive forefoot surgery (MIS), particularly hallux valgus correction, has significantly advanced with the introduction of the Shannon burr. However, despite numerous relevant studies being published, no comprehensive review articles have summarized MIS for various forefoot conditions. Therefore, in this comprehensive review, we examined the relevant studies about the application of MIS (excluding arthroscopy and endoscopy) for various forefoot conditions. Additionally, we discuss the essential considerations for achieving favorable surgical outcomes and preventing complications associated with each technique. We analyzed the characteristics of each surgical procedure and identified areas for future focus. Effective surgical treatment not only requires MIS, but also the appropriate selection of patients based on suitable indications and executing procedures within the surgeon's capabilities. We hope that this review will help readers to enhance their expertise in this field.

7.
J Magn Reson Imaging ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39238277

RESUMEN

BACKGROUND: The specific patterns of subependymal enhancement (SE) that frequently occur as radiation-induced changes in high-grade gliomas following radiotherapy are often overlooked. Perfusion MRI may offer a diagnostic clue. PURPOSE: To distinguish between radiation-induced SE and progression in adult high-grade diffuse gliomas after standard treatment. STUDY TYPE: Retrospective. POPULATION: Ninety-four consecutive high-grade diffuse glioma patients (mean age, 55 ± 14 years; 54 [57.4%] males) with new SE identified in follow-up MRI after completion of surgery plus chemoradiation: progression (N = 74) vs. regression (N = 20). FIELD STRENGTH/SEQUENCE: 3 T, gradient-echo dynamic susceptibility contrast-enhanced MRI, 3D gradient-echo contrast-enhanced T1-weighted imaging. ASSESSMENT: To differentiate between radiation changes and progression in SE evaluation, multivariable logistic regression was performed using significant variables among SE appearance interval, IDH mutation, morphological features, and rCBV. Cox regression was performed to predict the tumor progression. For the added value of the rCBV, a log-rank test was conducted between the multivariable logistic regression models with and without the rCBV. STATISTICAL TESTS: Logistic regression, Cox regression, receiver operating characteristic analysis, log-rank test. RESULTS: 38.3% (36/94) patients had first specific SE (9.2 ± 9.5 months after surgery), which disappeared in 21.3% (20/94) after 5.8 ± 5.8 months after initial appearance on post-radiation MRI. IDH mutation, elongated, small lesions with lower rCBV tended to regress: IDH mutation, elongation, diameter, and rCBV_p95; odds ratio, 0.32, 1.92, 1.70, and 2.47, respectively. Qualitative evaluation of shape revealed that thin and curvilinear-shaped SE tended to regress, indicating a significant correlation with quantitative shape features (r = 0.31). In Cox regression, rCBV and lesion shape were significant (hazard ratio = 1.09 and 0.54, respectively). For sub-centimeter lesions, the rCBV showed added value in predicting outcomes (area under the curve, 0.873 vs. 0.836; log-rank test). DATA CONCLUSION: Smaller, elongated lesions with lower rCBV and IDH mutation are associated with regression when differentiating radiation changes from progression in high-grade glioma with post-radiotherapy SE. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

8.
Artículo en Inglés | MEDLINE | ID: mdl-39218203

RESUMEN

OBJECTIVE: AMP-activated protein kinase (AMPK) dysregulation is implicated in osteoarthritis (OA), but the mechanisms underlying this dysregulation remain unclear. We investigated the role of cereblon, a substrate-recognition protein within the E3-ligase ubiquitin complex, in AMPK dysregulation and OA pathogenesis. METHODS: Cereblon expression was examined in human (n = 5) and mouse (n = 10) OA cartilage. The role of cereblon was investigated through its adenoviral overexpression (n = 10) or knockout (KO, n = 15) in the destabilization of the medial meniscus (DMM)-operated mice. The therapeutic potentials of the chemical cereblon degrader, TD-165, and the AMPK activator, metformin, were assessed through intra-articular (IA) injection to mice (n = 15). RESULTS: Immunostaining revealed that cereblon is upregulated in human and mouse OA cartilage. In DMM model mice, cartilage destruction was exacerbated by overexpression of cereblon in mouse joint tissues (OARSI grade; 1.11 [95% CI: 0.50 to 2.75]), but inhibited in global (-2.50 [95% CI: -3.00 to -1.17]) and chondrocyte-specific (-2.17 [95% CI: -3.14 to -1.06]) cereblon KO mice. The inhibitory effects were more pronounced in mice fed a high-fat diet compared to a regular diet. The degradation of cereblon through IA injection of TD-165 inhibited OA cartilage destruction (-2.47 [95% CI: -3.22 to -1.56]). Mechanistically, cereblon exerts its catabolic effects by negatively modulating AMPK activity within chondrocytes. Consistently, activation of AMPK by IA injection of metformin inhibited posttraumatic OA cartilage destruction (-1.20 ([95% CI: -1.89 to -0.45]). CONCLUSIONS: The cereblon-AMPK axis acts as a catabolic regulator of OA pathogenesis and seems to be a promising therapeutic target in animal models of OA.

10.
J Clin Med ; 13(16)2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39200945

RESUMEN

Background: Recent studies utilizing weight-bearing computed tomography have identified abnormal internal rotation of the talus in advanced varus ankle arthritis (VAA) with a large talar tilt (TT), influenced by the posterior tibial tendon (PTT). This study aimed to evaluate the clinical and radiographic results of supramalleolar osteotomy (SMO) combined with PTT release and lateral ligament augmentation for VAA with a large TT. Methods: From January 2015 to September 2018, 15 patients with VAA and a large TT (greater than 5°) underwent SMO combined with PTT release. Clinical results, including visual analog scale (VAS) for pain, American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and ankle osteoarthritis scale (AOS), were assessed. Radiographic results were assessed with various parameters, including medial distal tibial angle (MDTA), anterior distal tibial angle (ADTA), talar tilt (TT), talus center migration (TCM), Meary angle, hindfoot alignment angle (HAA), and hindfoot moment arm (HMA) on foot and ankle weight-bearing radiographs. Clinical and radiographic results were evaluated preoperatively and at the last follow-up. Results: VAS, AOFAS ankle-hindfoot score, and AOS improved significantly from 7.5, 54.4, and 72.6 preoperatively to 3.1, 82.5, and 34.5 postoperatively, respectively. All radiographic parameters exhibited significant changes postoperatively, with the exception of the Meary angle, which demonstrated no significant change. Four patients exhibited improvement in radiographic stage postoperatively; however, average radiographic stage did not significantly improve postoperatively in all patients. One patient progressed to end-stage arthritis postoperatively, necessitating additional ankle arthrodesis. Conclusions: In conclusion, lengthening and lateral ligament augmentation combined with bony realignment procedures may be a reasonable option for treating VAA with a large TT greater that 5°.

11.
J Plast Reconstr Aesthet Surg ; 96: 256-262, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39116803

RESUMEN

BACKGROUND: Certain auricular malformations are uncommon and lack generally accepted diagnostic names. This study investigates an uncommon complex auricular malformation known as auricular spoon-shaped crus malformation providing a detailed description of its external characteristics. Additionally, an effective surgical approach is proposed. METHODS: Between 1991 and 2023, 12 auricles in 11 patients with auricular spoon-shaped crus malformation including variants were surgically treated at our center. Patient medical records and photographic data were retrospectively reviewed. RESULTS: Each auricle exhibited 2 to 4 major structural deformities within the 5 areas of the superior crus, inferior crus, and stem of the antihelix, helical crus, and earlobe. These deformities resulted in depression between the antihelix and antitragus, vertical shortening, horizontal elongation of the auricle, and/or drooping of the ear. Three patients displayed a low positioning of the malformed ear, and 8 patients exhibited mild to moderate hemifacial microsomia. In corrections we conducted earlier, we utilized various methods with variable aesthetic outcomes. Recently, an improved corrective method we implemented yielded consistently promising aesthetic results. We have confidence that adopting the surgical approach we suggest can lead to promising aesthetic results when addressing this malformation. Furthermore, we hope that the presented malformation will be recognized as a primary auricular malformation by auricular surgeons in the future.


Asunto(s)
Pabellón Auricular , Humanos , Masculino , Femenino , Pabellón Auricular/anomalías , Pabellón Auricular/cirugía , Estudios Retrospectivos , Niño , Adolescente , Procedimientos de Cirugía Plástica/métodos , Preescolar , Estética , Adulto , Adulto Joven , Resultado del Tratamiento , Oído Externo/anomalías , Oído Externo/cirugía
12.
Ecotoxicol Environ Saf ; 283: 116838, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39128447

RESUMEN

The number of individuals with underlying medical conditions has been increasing steadily. These individuals are relatively vulnerable to harmful external factors. But it has not been proven that the effects of hazardous chemicals may differ depending on their physicochemical properties. This study determines the toxic effects of two chemicals with high indoor exposure risk and different physicochemical properties on an underlying disease model. A pulmonary arterial hypertension (PAH) model was constructed by a single subcutaneous injection of monocrotaline (MCT; 60 mg/kg) into Sprague-Dawley rats. After three weeks, formaldehyde (FA; 2.5 mg/kg) and polyhexamethylene guanidine (PHMG; 0.05 mg/kg) were administered once via intratracheal instillation, and rats were necropsied one week later. Exposure to FA and PHMG affected organ weight and the Fulton and toxicity indices in rats induced with PAH. FA promoted bronchial injury and aggravated PAH, while PHMG only induced alveolar injury. Additionally, the differentially expressed genes were altered following exposure to FA and PHMG, as were the associated diseases (cardiovascular disease and pulmonary fibrosis, respectively). In conclusion, inhaled chemicals with different physicochemical properties can cause damage to organs, such as the lungs and heart, and can aggravate underlying diseases. This study elucidates indoor inhaled exposure-induced toxicities and alerts patients with pre-existing diseases to the harmful chemicals.


Asunto(s)
Modelos Animales de Enfermedad , Formaldehído , Lesión Pulmonar , Ratas Sprague-Dawley , Animales , Ratas , Masculino , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/patología , Formaldehído/toxicidad , Guanidinas/toxicidad , Monocrotalina/toxicidad , Exposición por Inhalación , Pulmón/efectos de los fármacos , Pulmón/patología , Hipertensión Arterial Pulmonar/inducido químicamente , Sustancias Peligrosas/toxicidad
13.
Int Orthop ; 48(10): 2727-2734, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39060509

RESUMEN

PURPOSE: The authors experienced several cases of extra-articular calcaneal fracture accompanied by joint depression involving the entire posterior facet without joint involvement. This type of fracture and its characteristics and treatment outcomes have not been previously reported. The study was performed to analyze the characteristics of extra-articular calcaneal fractures of the joint depression type and their postoperative clinical and radiographic results and complications. METHODS: Between February 2013 and March 2021, 23 extra-articular calcaneal fractures of the joint depression type were consecutively treated by a single surgeon. Relationships between fracture characteristics and patient demographics were assessed. Clinical results were quantified using visual analog scale, American Orthopaedic Foot and Ankle Society ankle-hindfoot scale, and Foot Function Index, radiographic results were evaluated using Böhler's angles, and calcaneal widths were determined using calcaneal axial and lateral radiographs obtained preoperatively and at last follow-up. RESULTS: Twenty (87%) of the 23 cases occurred in women, and the mean age of all patients was 65.8 years (43-90). The three men were older than 65. Five (21.7%) patients had osteopenia, and 12 (52.2%) had osteoporosis. Bone mineral density testing could not be performed in the other six patients. Clinical and radiographic results were significantly improved after surgery. CONCLUSION: Extra-articular calcaneal fractures of the joint depression type are much more common in women and occur at an older age than calcaneal fractures commonly occur. These fractures are also more common in patients with a low bone mineral density. LEVEL OF EVIDENCE: Level IV.


Asunto(s)
Calcáneo , Fracturas Óseas , Osteoporosis , Humanos , Calcáneo/lesiones , Calcáneo/diagnóstico por imagen , Calcáneo/cirugía , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Anciano de 80 o más Años , Osteoporosis/complicaciones , Fracturas Óseas/complicaciones , Fracturas Óseas/cirugía , Fijación Interna de Fracturas/métodos , Envejecimiento/fisiología , Resultado del Tratamiento , Radiografía/métodos , Estudios Retrospectivos
14.
Biomed Pharmacother ; 178: 117157, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39042964

RESUMEN

Although the potent anti-inflammatory effects of irisin have been documented in various inflammatory disorders, its efficacy against inflammatory pain remains unexplored. Herein, we examined the therapeutic effects of irisin in a mouse model of inflammatory pain induced by complete Freund's adjuvant (CFA). Mice were divided into three groups: normal control, CFA-injected (CFA), and CFA plus irisin-treated (CFA+Irisin). The irisin-treated group exhibited a gradual reduction in mechanical allodynia and thermal hyperalgesia when compared with the CFA group. Moreover, treatment with irisin significantly upregulated the expression of M2 macrophage markers (interleukin [IL]-4 and IL-10) and downregulated M1 macrophage markers (IL-1ß, IL-6, and tumor necrosis factor-α) in the local paw tissue, dorsal root ganglion, and spinal cord tissue. However, there was no significant difference in the total number of F4/80+ macrophages in the paw tissue and dorsal root ganglion, indicating phenotypic exchange. Treatment with irisin also downregulated the expression of the glial cell activation-related markers Iba-1 and GFAP in the spinal cord tissue. To elucidate the underlying mechanisms, we detected the expression of Toll-like receptor 4 (TLR4), MyD88, and interferon regulatory factor 5 (IRF5) in paw tissues, dorsal root ganglion, and spinal tissues, revealing that irisin could downregulate the expression of these proteins. Irisin alleviated inflammatory pain by modulating local tissue inflammation and peripheral and central neuroinflammation and reducing glial cell activation and M2 macrophage polarization by modulating the TLR4-MyD88-IRF5 signaling pathway. Accordingly, irisin is a promising candidate for treating inflammatory pain in various diseases.


Asunto(s)
Fibronectinas , Adyuvante de Freund , Inflamación , Macrófagos , Neuroglía , Médula Espinal , Animales , Fibronectinas/metabolismo , Masculino , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/patología , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Ratones Endogámicos C57BL , Dolor/tratamiento farmacológico , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Activación de Macrófagos/efectos de los fármacos , Antiinflamatorios/farmacología , Receptor Toll-Like 4/metabolismo , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos
15.
Acta Neuropathol Commun ; 12(1): 118, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014476

RESUMEN

Background Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are found in 1% of gliomas across children and adults. TRK inhibitors are promising therapeutic agents for NTRK-fused gliomas because they are tissue agnostic and cross the blood-brain barrier (BBB). Methods We investigated twelve NGS-verified NTRK-fused gliomas from a single institute, Seoul National University Hospital. Results The patient cohort included six children (aged 1-15 years) and six adults (aged 27-72 years). NTRK2 fusions were found in ten cerebral diffuse low-grade and high-grade gliomas (DLGGs and DHGGs, respectively), and NTRK1 fusions were found in one cerebral desmoplastic infantile ganglioglioma and one spinal DHGG. In this series, the fusion partners of NTRK2 were HOOK3, KIF5A, GKAP1, LHFPL3, SLMAP, ZBTB43, SPECC1L, FKBP15, KANK1, and BCR, while the NTRK1 fusion partners were TPR and TPM3. DLGGs tended to harbour only an NTRK fusion, while DHGGs exhibited further genetic alterations, such as TERT promoter/TP53/PTEN mutation, CDKN2A/2B homozygous deletion, PDGFRA/KIT/MDM4/AKT3 amplification, or multiple chromosomal copy number aberrations. Four patients received adjuvant TRK inhibitor therapy (larotrectinib, repotrectinib, or entrectinib), among which three also received chemotherapy (n = 2) or proton therapy (n = 1). The treatment outcomes for patients receiving TRK inhibitors varied: one child who received larotrectinib for residual DLGG maintained stable disease. In contrast, another child with DHGG in the spinal cord experienced multiple instances of tumour recurrence. Despite treatment with larotrectinib, ultimately, the child died as a result of tumour progression. An adult patient with glioblastoma (GBM) treated with entrectinib also experienced tumour progression and eventually died. However, there was a successful outcome for a paediatric patient with DHGG who, after a second gross total tumour removal followed by repotrectinib treatment, showed no evidence of disease. This patient had previously experienced relapse after the initial surgery and underwent autologous peripheral blood stem cell therapy with carboplatin/thiotepa and proton therapy. Conclusions Our study clarifies the distinct differences in the pathology and TRK inhibitor response between LGG and HGG with NTRK fusions.


Asunto(s)
Inhibidores de Proteínas Quinasas , Pirazoles , Receptor trkB , Humanos , Masculino , Femenino , Niño , Preescolar , Adulto , Adolescente , Persona de Mediana Edad , Anciano , Lactante , Receptor trkB/genética , Receptor trkB/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Pirazoles/uso terapéutico , Receptor trkA/genética , Receptor trkA/antagonistas & inhibidores , Glioma/genética , Glioma/patología , Glioma/tratamiento farmacológico , Pirimidinas/uso terapéutico , Proteínas de Fusión Oncogénica/genética , Benzamidas/uso terapéutico , Glicoproteínas de Membrana/genética , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Indazoles
16.
Cancers (Basel) ; 16(11)2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38893152

RESUMEN

Mutation in the telomerase reverse transcriptase promoter (TERTp )is commonly observed in various malignancies, such as central nervous system (CNS) tumors, malignant melanoma, bladder cancer, and thyroid carcinoma. These mutations are recognized as significant poor prognostic factors for these tumors. In this investigation, a total of 528 cases of adult-type diffuse gliomas diagnosed at a single institution were reclassified according to the 2021 WHO classifications of CNS tumors, 5th edition (WHO2021). The study analyzed clinicopathological and genetic features, including TERTp mutations in each tumor. The impact of known prognostic factors on patient outcomes was analyzed through Kaplan-Meier survival and Cox regression analysis. TERTp mutations were predominantly identified in 94.1% of oligodendrogliomas (ODG), followed by 66.3% in glioblastoma, IDH-wildtype (GBM-IDHwt), and 9.2% of astrocytomas, IDH-mutant (A-IDHm). When considering A-IDHm and GBM as astrocytic tumors (Group 1) and ODGs (Group 2), TERTp mutations emerged as a significant adverse prognostic factor (p = 0.013) in Group 1. However, within each GBM-IDHwt and A-IDHm, the presence of TERTp mutations did not significantly impact patient prognosis (p = 0.215 and 0.268, respectively). Due to the high frequency of TERTp mutations in Group 2 (ODG) and their consistent prolonged survival, a statistical analysis to evaluate their impact on overall survival was deemed impractical. When considering MGMTp status, the combined TERTp-mutated and MGMTp-unmethylated group exhibited the worst prognosis in OS (p = 0.018) and PFS (p = 0.034) of GBM. This study confirmed that the classification of tumors according to the WHO2021 criteria effectively reflected prognosis. Both uni- and multivariate analyses in GBM, age, MGMTp methylation, and CDKN2A/B homozygous deletion were statistically significant prognostic factors while in univariate analysis in A-IDHm, grade 4, the Ki-67 index and MYCN amplifications were statistically significant prognostic factors. This study suggests that it is important to classify and manage tumors based on their genetic characteristics in adult-type diffuse gliomas.

18.
J Pathol Transl Med ; 58(3): 141-145, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38766740

RESUMEN

An aggressive subtype of inflammatory myofibroblastic tumor, epithelioid inflammatory myofibroblastic sarcoma occurs primarily inside the abdominal cavity, followed by a pulmonary localization. Most harbor anaplastic lymphoma kinase (ALK) gene rearrangements, with RANBP2 and RRBP1 among the well-documented fusion partners. We report the second case of primary epithelioid inflammatory myofibroblastic sarcoma of the brain, with a well-known EML4::ALK fusion. The case is notable for its intra-axial presentation that clinico-radiologically mimicked glioma.

19.
Radiology ; 311(2): e233120, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38713025

RESUMEN

Background According to 2021 World Health Organization criteria, adult-type diffuse gliomas include glioblastoma, isocitrate dehydrogenase (IDH)-wildtype; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and astrocytoma, IDH-mutant, even when contrast enhancement is lacking. Purpose To develop and validate simple scoring systems for predicting IDH and subsequent 1p/19q codeletion status in gliomas without contrast enhancement using standard clinical MRI sequences. Materials and Methods This retrospective study included adult-type diffuse gliomas lacking contrast at contrast-enhanced MRI from two tertiary referral hospitals between January 2012 and April 2022 with diagnoses confirmed at pathology. IDH status was predicted primarily by using T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign, followed by 1p/19q codeletion prediction. A visual rating of MRI features, apparent diffusion coefficient (ADC) ratio, and relative cerebral blood volume was measured. Scoring systems were developed through univariable and multivariable logistic regressions and underwent calibration and discrimination, including internal and external validation. Results For the internal validation cohort, 237 patients were included (mean age, 44.4 years ± 14.4 [SD]; 136 male patients; 193 patients in IDH prediction and 163 patients in 1p/19q prediction). For the external validation cohort, 35 patients were included (46.1 years ± 15.3; 20 male patients; 28 patients in IDH prediction and 24 patients in 1p/19q prediction). The T2-FLAIR mismatch sign demonstrated 100% specificity and 100% positive predictive value for IDH mutation. IDH status prediction scoring system for tumors without mismatch sign included age, ADC ratio, and morphologic characteristics, whereas 1p/19q codeletion prediction for IDH-mutant gliomas included ADC ratio, cortical involvement, and mismatch sign. For IDH status and 1p/19q codeletion prediction, bootstrap-corrected areas under the receiver operating characteristic curve were 0.86 (95% CI: 0.81, 0.90) and 0.73 (95% CI: 0.65, 0.81), respectively, whereas at external validation they were 0.99 (95% CI: 0.98, 1.0) and 0.88 (95% CI: 0.63, 1.0). Conclusion The T2-FLAIR mismatch sign and scoring systems using standard clinical MRI predicted IDH and 1p/19q codeletion status in gliomas lacking contrast enhancement. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Badve and Hodges in this issue.


Asunto(s)
Deleción Cromosómica , Isocitrato Deshidrogenasa , Imagen por Resonancia Magnética , Mutación , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico por imagen , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 19/genética , Medios de Contraste , Glioma/genética , Glioma/diagnóstico por imagen , Isocitrato Deshidrogenasa/genética , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos
20.
Ann Surg Oncol ; 31(8): 5021-5027, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38557912

RESUMEN

BACKGROUND: For patients with left upper lobe lesions, the functional benefit of left upper division segmentectomy over left upper lobectomy remains controversial. This study evaluated the clinical and functional outcomes after these two procedures. METHODS: This retrospective study included 135 patients with left upper lobe lesions (left upper lobectomy, 110; left upper division segmentectomy, 25). Propensity score matching was used to compare the two groups. Spirometry and computed tomography volume assessments were performed to evaluate bronchus angle and tortuosity. Short-term clinical respiratory symptoms were assessed via medical record reviews. RESULTS: Patients in both groups had similar preoperative characteristics, apart from tumor size (left upper division segmentectomy, 1.6 ± 0.9 cm; left upper lobectomy, 2.8 ± 1.7 cm; p = 0.002). After propensity score matching, both groups had similar preoperative spirometry and pathological results. The postoperative spirometry results were similar; however, the left upper division segmentectomy group had a significantly smaller decrease in left-side computed tomography lung volume compared with that in the left upper lobectomy group (left upper division segmentectomy, 323.6 ± 521.4 mL; left upper lobectomy, 690.7 ± 332.8 mL; p = 0.004). The left main bronchus-curvature index was higher in the left upper lobectomy group (left upper division segmentectomy, 1.074 ± 0.035; left upper lobectomy, 1.097 ± 0.036; p = 0.013), and more patients had persistent cough in the left upper lobectomy group (p = 0.001). CONCLUSIONS: Left upper division segmentectomy may be a promising option for preventing marked bronchial angulation and decreasing postoperative persistent cough in patients with left upper lobe lung cancer.


Asunto(s)
Bronquios , Neoplasias Pulmonares , Neumonectomía , Humanos , Masculino , Femenino , Neumonectomía/métodos , Estudios Retrospectivos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico por imagen , Bronquios/cirugía , Bronquios/patología , Persona de Mediana Edad , Anciano , Estudios de Seguimiento , Tomografía Computarizada por Rayos X , Pronóstico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Pulmón/cirugía , Pulmón/diagnóstico por imagen
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