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PURPOSE: Despite the effectiveness of 177Lu-based peptide receptor radionuclide therapy in treating metastatic neuroendocrine tumors (NETs), disease progression posttreatment remains a significant challenge. Targeted alpha therapy (TAT) has emerged as a promising option for patients experiencing such progression. This study aims to assess the therapeutic efficiency and toxicity of TAT in patients with metastatic NET through a meta-analysis. PATIENTS AND METHODS: We conducted a comprehensive search of PubMed, Embase, Cochrane Library, and CINAHL using relevant keywords. The analysis focused on the pooled proportions of objective response rate (ORR) and disease control rate (DCR) to determine therapeutic efficiency. We also evaluated the incidence of serious hematologic and renal adverse events (grade 3 or 4) to assess toxicity. A subgroup analysis was performed to identify factors influencing therapeutic outcomes. RESULTS: Our meta-analysis included 7 studies comprising 162 patients. The results showed that TAT achieved ORR of 49.5% (95% confidence interval [CI]: 41.7%-57.4%) and DCR of 87.0% (95% CI: 72.1%-96.8%). The incidences of hematologic and renal toxicities were low, at 2.1% (95% CI: 0.5%-5.5%) and 3.4% (95% CI: 1.2%-7.3%), respectively. Subgroup analysis indicated consistent therapeutic efficiency across different variables, including prior 177Lu-based peptide receptor radionuclide therapy treatment, 225Ac-based TAT, absence of radiosensitizer, and methods of response evaluation, with ORR ranging from 46.6% to 57.1% and DCR from 82.0% to 91.5%. CONCLUSIONS: TAT is an effective treatment for metastatic NET, demonstrating substantial disease control and response rates with minimal toxicity. These findings suggest that TAT is a viable therapeutic alternative for patients with metastatic NET.
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OBJECTIVES: [18F]Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is a non-invasive imaging modality used in the differential diagnosis of splenic lesions, although ideal parameters and thresholds remain unclear. The present study evaluated the ability of [18F]FDG PET/CT, including its visual and quantitative parameters, to differentiate between benign and malignant splenic lesions. METHODS: Patients who underwent [18F]FDG PET/CT following the detection of splenic lesions on contrast-enhanced CT were retrospectively analysed. Visual parameters assessed on [18F]FDG PET/CT included whole spleen uptake intensity, lesion multiplicity, and lesion uptake, and quantitative parameters included maximum standardised uptake value (SUVmax), lesion-to-background ratio (LBR), metabolic tumour volume (MTV), total lesion glycolysis (TLG), and lesion size. Parameters differentiating between benign and malignant lesions were evaluated by Pearson's chi-square test, Mann-Whitney U-test, and receiver operating characteristics (ROC) curve analysis. RESULTS: Splenic lesion uptake (p = 0.001) was the only visual parameter significantly distinguishing between benign and malignant lesions. ROC curve analysis demonstrated that SUVmax had the largest area under the ROC, 0.91 (p < 0.001), with an optimal cut-off > 5.3 having a sensitivity of 90.3% and a specificity of 80.6%. Subgroup analysis of malignant lesions showed that SUVmax (p = 0.013), LBR (p = 0.012), and TLG (p = 0.034) were significantly higher in splenic lymphomas than in splenic metastases. CONCLUSION: Of the [18F]FDG PET/CT parameters investigated, SUVmax had the highest accuracy in diagnosing malignant splenic lesions and was significantly higher in splenic lymphomas than in splenic metastases. Visual determination of [18F]FDG uptake by splenic lesions may be an easily evaluated parameter. CLINICAL RELEVANCE STATEMENT: SUVmax and visual grade of [18F]FDG PET/CT help to differentiate spleen lesions. [18F]FDG PET/CT is useful for discriminating between benign and malignant spleen lesions. KEY POINTS: Many splenic lesions are difficult to diagnose on anatomical imaging, with histopathologic analyses are required. SUVmax of PET/CT provided the diagnostic ability to differentiate between benign and malignant splenic lesions. More than normal spleen uptake can be a convenient parameter to diagnose malignant spleen lesions.
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Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [68Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [68Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.
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Isótopos de Galio , Radioisótopos de Galio , Recurrencia Local de Neoplasia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/sangre , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Antígeno Prostático Específico/sangre , Ácido Edético/análogos & derivados , OligopéptidosRESUMEN
Piezoelectric fiber yarns produced by electrospinning offer a versatile platform for intelligent devices, demonstrating mechanical durability and the ability to convert mechanical strain into electric signals. While conventional methods involve twisting a single poly(vinylidene fluoride-co-trifluoroethylene)(P(VDF-TrFE)) fiber mat to create yarns, by limiting control over the mechanical properties, an approach inspired by composite laminate design principles is proposed for strengthening. By stacking multiple electrospun mats in various sequences and twisting them into yarns, the mechanical properties of P(VDF-TrFE) yarn structures are efficiently optimized. By leveraging a multi-objective Bayesian optimization-based machine learning algorithm without imposing specific stacking restrictions, an optimal stacking sequence is determined that simultaneously enhances the ultimate tensile strength (UTS) and failure strain by considering the orientation angles of each aligned fiber mat as discrete design variables. The conditions on the Pareto front that achieve a balanced improvement in both the UTS and failure strain are identified. Additionally, applying corona poling induces extra dipole polarization in the yarn state, successfully fabricating mechanically robust and high-performance piezoelectric P(VDF-TrFE) yarns. Ultimately, the mechanically strengthened piezoelectric yarns demonstrate superior capabilities in self-powered sensing applications, particularly in challenging environments and sports scenarios, substantiating their potential for real-time signal detection.
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BACKGROUND: Thymic cysts are a rare benign disease that needs to be distinguished from low-risk thymoma. [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a non-invasive imaging technique used in the differential diagnosis of thymic epithelial tumours, but its usefulness for thymic cysts remains unclear. Our study evaluated the utility of visual findings and quantitative parameters of [18F]FDG PET/CT for differentiating between thymic cysts and low-risk thymomas. METHODS: Patients who underwent preoperative [18F]FDG PET/CT followed by thymectomy for a thymic mass were retrospectively analyzed. The visual [18F]FDG PET/CT findings evaluated were PET visual grade, PET central metabolic defect, and CT shape. The quantitative [18F]FDG PET/CT parameters evaluated were PET maximum standardized uptake value (SUVmax), CT diameter (cm), and CT attenuation in Hounsfield units (HU). Findings and parameters for differentiating thymic cysts from low-risk thymomas were assessed using Pearson's chi-square test, the Mann-Whitney U-test, and receiver operating characteristics (ROC) curve analysis. RESULTS: Seventy patients (18 thymic cysts and 52 low-risk thymomas) were finally included. Visual findings of PET visual grade (P < 0.001) and PET central metabolic defect (P < 0.001) showed significant differences between thymic cysts and low-risk thymomas, but CT shape did not. Among the quantitative parameters, PET SUVmax (P < 0.001), CT diameter (P < 0.001), and CT HU (P = 0.004) showed significant differences. In ROC analysis, PET SUVmax demonstrated the highest area under the curve (AUC) of 0.996 (P < 0.001), with a cut-off of equal to or less than 2.1 having a sensitivity of 100.0% and specificity of 94.2%. The AUC of PET SUVmax was significantly larger than that of CT diameter (P = 0.009) and CT HU (P = 0.004). CONCLUSIONS: Among the [18F]FDG PET/CT parameters examined, low FDG uptake (SUVmax ≤ 2.1, equal to or less than the mediastinum) is a strong diagnostic marker for a thymic cyst. PET visual grade and central metabolic defect are easily accessible findings.
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Various electrocatalysts are extensively examined for their ability to selectively produce desired products by electrochemical CO2 reduction reaction (CO2RR). However, an efficient CO2RR electrocatalyst doesn't ensure an effective co-catalyst on the semiconductor surface for photoelectrochemical CO2RR. Herein, Bi2S3 nanorods are synthesized and electrochemically reduced to Bi nanoplates that adhere to the substrates for application in the electrochemical and photoelectrochemical CO2RR. Compared with commercial-Bi, the Bi2S3-derived Bi (S-Bi) nanoplates on carbon paper exhibit superior electrocatalytic activity and selectivity for formate (HCOO-) in the electrochemical CO2RR, achieving a Faradaic efficiency exceeding 93%, with minimal H2 production over a wide potential range. This highly selective S-Bi catalyst is being employed on the Si photocathode to investigate the behavior of electrocatalysts during photoelectrochemical CO2RR. The strong adhesion of the S-Bi nanoplates to the Si nanowire substrate and their unique catalytic properties afford exceptional activity and selectivity for HCOO- under simulated solar irradiation. The selectivity observed in electrochemical CO2RR using the S-Bi catalyst correlates with that seen in the photoelectrochemical CO2RR system. Combined pulsed potential methods and theoretical analyses reveal stabilization of the OCHO* intermediate on the S-Bi catalyst under specific conditions, which is critical for developing efficient catalysts for CO2-to-HCOO- conversion.
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BACKGROUND: The Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis 2023 was extensively revised to reflect the latest advances in antineoplastic agents, antiemetics, and antineoplastic regimens. This update provides new evidence on the efficacy of antiemetic regimens. METHODS: Guided by the Minds Clinical Practice Guideline Development Manual of 2017, a rigorous approach was used to update the guidelines; a thorough literature search was conducted from January 1, 1990, to December 31, 2020. RESULTS: Comprehensive process resulted in the creation of 13 background questions (BQs), 12 clinical questions (CQs), and three future research questions (FQs). Moreover, the emetic risk classification was also updated. CONCLUSIONS: The primary goal of the present guidelines is to provide comprehensive information and facilitate informed decision-making, regarding antiemetic therapy, for both patients and healthcare providers.
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Antieméticos , Oncología Médica , Vómitos , Humanos , Japón , Oncología Médica/normas , Antieméticos/uso terapéutico , Vómitos/prevención & control , Vómitos/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Sociedades Médicas , Náusea/prevención & control , Náusea/tratamiento farmacológicoRESUMEN
BACKGROUND: Anticipatory chemotherapy-induced nausea and vomiting (CINV) is a conditioned response influenced by the severity and duration of previous emetic responses to chemotherapy. We aimed to evaluate the efficacy of non-pharmacologic interventions for anticipatory CINV among patients with cancer. METHODS: We conducted a systematic search in databases, including PubMed, the Cochrane Library, CINAHL, and Ichushi-Web, from January 1, 1990, to December 31, 2020. Randomized controlled trials, non-randomized designs, observational studies, or case-control studies that utilized non-pharmacological therapies were included. The primary outcomes were anticipatory CINV, with an additional investigation into adverse events and the costs of therapies. The risk-of-bias for each study was assessed using the Cochrane risk-of-bias tool, and meta-analysis was performed using Revman 5.4 software. RESULTS: Of the 107 studies identified, six met the inclusion criteria. Three types of non-pharmacological treatments were identified: systematic desensitization (n = 2), hypnotherapy (n = 2), and yoga therapy (n = 2). Among them, systematic desensitization significantly improved anticipatory CINV as compared to that in the control group (nausea: risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.49-0.72, p < 0.00001; vomiting: RR = 0.54, 95% CI = 0.32-0.91, p = 0.02). However, heterogeneity in outcome measures precluded meta-analysis for hypnotherapy and yoga. Additionally, most selected studies had a high or unclear risk of bias, and adverse events were not consistently reported. CONCLUSIONS: Our findings suggest that systematic desensitization may effectively reduce anticipatory CINV. However, further research is warranted before implementation in clinical settings.
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Antineoplásicos , Náusea , Neoplasias , Humanos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Náusea/inducido químicamente , Náusea/prevención & control , Neoplasias/tratamiento farmacológico , Vómitos/inducido químicamente , Vómitos/prevención & control , Vómitos/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Vómito Precoz , Hipnosis , Yoga , Antieméticos/uso terapéuticoRESUMEN
A light-weight actuator developed in this work belongs to a class of soft robots, and in a sense, resembles an octopus. Its main function is in the attachment or detachment to a solid surface driven by an electro-thermopneumatic mechanism. In this study, a suction cup similar to that of an octopus is manufactured from an elastomer, which is actuated by an electro-thermopneumatic system, mimicking the movement of the octopus' acetabular muscle. Accordingly, the adhesion force generated by such an actuator is regulated by releasing the inner air or adjusting the cup's elasticity. This actuator is designed to be an assistive device that facilitates the individual's physical strength in case of conditions related to aging or cerebellar disease, or a person who lost limbs. In this study, the actuator capabilities are demonstrated in the form of a grip-assisting glove and prosthetic attacher. Moreover, the adhesion mechanism is quantified by numerical simulations and verified experimentally.
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Soluble epoxide hydrolase (sEH) is an enzyme targeted for the treatment of inflammation and cardiovascular diseases. Activated inflammatory cells produce nitric oxide (NO), which induces oxidative stress and exacerbates inflammation. We identify an inhibitor able to suppress sEH and thus NO production. Five flavonoids 1-5 isolated from Inula britannica flowers were evaluated for their abilities to inhibit sEH with IC50 values of 12.1 ± 0.1 to 62.8 ± 1.8 µM and for their effects on enzyme kinetics. A simulation study using computational chemistry was conducted as well. Furthermore, five inhibitors (1-5) were confirmed to suppress NO levels at 10 µM. The results showed that flavonoids 1-5 exhibited inhibitory activity in all tests, with compound 3 exhibiting the most significant efficacy. Thus, in the development of anti-inflammatory inhibitors, compound 3 is a promising natural candidate.
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Epóxido Hidrolasas , Flavonoides , Inula , Óxido Nítrico , Epóxido Hidrolasas/antagonistas & inhibidores , Epóxido Hidrolasas/metabolismo , Animales , Óxido Nítrico/metabolismo , Ratones , Células RAW 264.7 , Flavonoides/farmacología , Flavonoides/química , Flavonoides/aislamiento & purificación , Inula/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Simulación del Acoplamiento Molecular , Cinética , Antiinflamatorios/farmacología , Antiinflamatorios/química , Flores/químicaRESUMEN
Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.
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2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/computed tomography (CT) is known to be a helpful imaging modality for sacral chordoma, but its detailed characteristics have not been fully described. The purpose of our study was to identify the [18F]FDG PET/CT imaging characteristics of sacral chordoma and compare them with other sacral malignancy. This retrospective study included patients who underwent [18F]FDG PET/CT because of a mass involving the sacrum. Investigated visual findings included visual score and distribution, and semiquantitative parameters measured included standardized uptake values (SUVmax, SUVpeak, SUVmean), tumor-to-liver ratio (TLR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor size. Comparison studies and receiver operating characteristics (ROC) curve analysis were performed to differentiate between sacral chordoma and other sacral malignancy. Ten patients with sacral chordoma were finally included (M:Fâ =â 6:4, median ageâ =â 67 yr). On [18F]FDG PET/CT, sacral chordomas presented as a mass with minimal-moderate uptake with a usually heterogenous distribution. Compared with 12 patients with other sacral malignancies (M:Fâ =â 4:8, median age 42 yr), sacral chordoma showed a significantly lower TLR (median value 2.1 vs 6.3, Pâ =â .021). In ROC curve analysis, TLR showed the largest area under the curve (AUC) of 0.79 (cutoffâ ≤â 4.0; sensitivity 100.0%, specificity 58.3%; Pâ =â .004), and SUVmax showed the second largest AUC of 0.73 (cutoffâ ≤â 6.9; sensitivity 80.0%, specificity 66.7%; Pâ =â .034). [18F]FDG PET/CT of sacral chordoma showed minimal-moderate uptake. The TLR of [18F]FDG PET/CT was significantly lower than that of other sacral malignancy and was the most useful parameter for differentiating sacral chordoma, with the largest AUC. SUVmax could be another helpful semiquantitative parameter.
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Cordoma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Anciano , Adulto , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Cordoma/diagnóstico por imagen , Diagnóstico Diferencial , Sacro/diagnóstico por imagen , Estudios Retrospectivos , Carga Tumoral , RadiofármacosRESUMEN
BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE has shown efficacy in patients with metastatic neuroendocrine tumours (NETs). Personalised dosimetry is crucial to optimise treatment outcomes and minimise adverse events. In this study, we investigated the correlation between the tumour-absorbed dose (TAD) estimated from [177Lu]Lu-DOTA-TATE SPECT/CT and the therapeutic response. METHOD: A retrospective analysis was conducted on patients with advanced well-differentiated NETs grades 1-3 who underwent PRRT and exhibited greater uptake than liver on pre-therapeutic [68Ga]Ga-DOTA-TOC PET/CT. Target lesions were selected based on the RECIST 1.1 and PERCIST 1.0 criteria using [177Lu]Lu-DOTA-TATE SPECT/CT and pre-therapeutic contrast-enhanced CT scans. For anatomical image analysis, the sum of the longest diameter (SLD) of the target lesions was measured using the RECIST 1.1 criteria for patient-based analysis and the longest diameter (LD) of the target lesion using the RECIST-L criteria for lesion-based analysis. Standardised uptake values (SUVs) were measured on SPECT/CT images, and TADs were calculated based on the SUVs. Dosimetry was performed using a single SPECT/CT imaging time point at day 4-5 post-therapy. Statistical analyses were conducted to investigate correlations and determine the target lesion responses. RESULTS: Twenty patients with primary tumour sites and hepatic metastases were included. Fifty-five target lesions, predominantly located in the pancreas and liver, were analysed. The cumulative TAD (lesion-based analysis: r = 0.299-0.301, p = 0.025-0.027), but not the cycle 1 SUV (lesion-based analysis: r = 0.198-0.206, p = 0.131-0.147) or cycle 1 TAD (lesion-based analysis: r = 0.209-0.217, p = 0.112-0.126), exhibited a significant correlation with the change in LD of the target lesion. Binary logistic regression analysis identified the significance of the cumulative TAD in predicting disease control according to the RECIST-L criteria (odds ratio = 1.031-1.051, p = 0.024-0.026). CONCLUSIONS: The cumulative TAD estimated from [177Lu]Lu-DOTA-TATE SPECT/CT revealed a significant correlation with change in LD, which was significantly higher for the cumulative TAD than for the cycle 1 SUV or TAD. A higher cumulative TAD was associated with disease control in the target lesion. However, considering the limitations inherent to a confined sample size, careful interpretation of these findings is required. Estimation of the cumulative TAD of [177Lu]Lu-DOTA-TATE therapy could guide the platform towards personalised therapy.
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Somatostatin analogues have recently been used as therapeutic targets for metastatic or surgically unresectable gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), and associated somatostatin receptor (SSTR) expression has been well demonstrated in most GEP NETs, with the exception of rectal NETs. SSTR2 immunohistochemical expressions were evaluated in 350 surgically or endoscopically resected rectal NETs and compared to clinicopathologic factors. SSTR2 expression was observed in 234 (66.9%) rectal NET cases and associated tumors with smaller size (p = 0.001), low pT classification (p = 0.030), low AJCC tumor stage (p = 0.012), and absence of chromogranin expression (p = 0.009). Patients with rectal NET and SSTR2 expression had significantly better overall survival than those without SSTR2 expression both by univariable (p = 0.006) and multivariable (p = 0.014) analyses. In summary, approximately two-thirds of rectal NETs expressed SSTR2. SSTR2 expression was significantly associated with favorable behavior and good overall survival in patients with rectal NETs. Furthermore, SSTR2 expression can be used as prognostic factors. When metastatic disease occurs, SSTR2 expression can be used a possible target for somatostatin analogues.
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Neoplasias Intestinales , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Neoplasias del Recto , Neoplasias Gástricas , Humanos , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , Pronóstico , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Neoplasias del Recto/genética , Neoplasias del Recto/cirugía , Neoplasias del Recto/tratamiento farmacológico , Somatostatina/metabolismoRESUMEN
BACKGROUND: The increased expression of the nicotinic acetylcholine receptor (nAChR) in muscle denervation is thought to be associated with electrophysiological acetylcholine supersensitivity after nerve injury. Hence, we investigated the utility of the 18F-ASEM alpha7-nAChR targeting radiotracer as a new diagnostic method by visualizing skeletal muscle denervation in mouse models of sciatic nerve injury. METHODS: Ten-week-old C57BL/6 male mice were utilized. The mice were anesthetized, and the left sciatic nerve was resected after splitting the gluteal muscle. One week (n = 11) and three weeks (n = 6) after the denervation, 18F-ASEM positron emission tomography/magnetic resonance imaging (PET/MRI) was acquired. Maximum standardized uptake values (SUVmax) of the tibialis anterior muscle were measured for the denervated side and the control side. Autoradiographic evaluation was performed to measure the mean counts of the denervated and control tibialis anterior muscles at one week. In addition, immunohistochemistry was used to identify alpha7-nAChR-positive areas in denervated and control tibialis anterior muscles at one week (n = 6). Furthermore, a blocking study was conducted with methyllycaconitine (MLA, n = 5). RESULTS: 18F-ASEM PET/MRI showed significantly increased 18F-ASEM uptake in the denervated tibialis anterior muscle relative to the control side one week and three weeks post-denervation. SUVmax of the denervated muscles at one week and three weeks showed significantly higher uptake than the control (P = 0.0033 and 0.0277, respectively). The relative uptake by autoradiography for the denervated muscle was significantly higher than in the control, and immunohistochemistry revealed significantly greater alpha7-nAChR expression in the denervated muscle (P = 0.0277). In addition, the blocking study showed no significant 18F-ASEM uptake in the denervated side when compared to the control (P = 0.0796). CONCLUSIONS: Our results suggest that nAChR imaging with 18F-ASEM has potential as a noninvasive diagnostic method for peripheral nervous system disorders.
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PURPOSE: This study aimed to compare the diagnostic performances of 18 F-FDOPA PET/CT and 123 I-MIBG scintigraphy with SPECT/CT for detection of pheochromocytoma and paraganglioma (PPGL). PATIENTS AND METHODS: We conducted a prospective, single-institution comparative study. Patients suspected of having PPGL or those showing recurrence and/or distant metastasis of PPGL were enrolled. The primary objective was to affirm the noninferiority of 18 F-FDOPA PET/CT for diagnostic sensitivity. Both 123 I-MIBG scintigraphy with SPECT/CT (at 4 and 24 hours) and 18 F-FDOPA PET/CT (at 5 and 60 minutes after radiotracer administration) were performed. The final diagnosis was established either pathologically or via clinical follow-up. Nuclear physicians, unaware of the clinical data, undertook image analysis. RESULTS: Thirty-two patients were evaluated: 14 of 21 with an initial diagnosis and 9 of 11 with recurrence/metastasis had PPGLs in their final diagnoses. In patient-based analyses, 18 F-FDOPA PET/CT (95.7%) exhibited noninferior sensitivity compared with 123 I-MIBG SPECT/CT (91.3%), within the predetermined noninferiority margin of -12% by a 95% confidence interval lower limit of -10%. Both modalities showed no significant difference in specificity (88.9% vs 88.9%). In the region-based analysis for the recurrence/metastasis group, 18 F-FDOPA PET/CT demonstrated significantly higher sensitivity compared with 123 I-MIBG SPECT/CT (86.2% vs 65.5%, P = 0.031) and superior interobserver agreement (κ = 0.94 vs 0.85). The inclusion of an early phase in dual-phase 18 F-FDOPA PET/CT slightly improved diagnostic performance, albeit not to a statistically significant degree. CONCLUSIONS: 18 F-FDOPA PET/CT demonstrated noninferior sensitivity and comparable specificity to 123 I-MIBG SPECT/CT in the diagnosing PPGL. Notably, in the assessment of PPGL recurrence and metastasis, 18 F-FDOPA PET/CT outperformed 123 I-MIBG SPECT/CT in terms of both sensitivity and interobserver agreement.
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Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Humanos , 3-Yodobencilguanidina , Neoplasias de las Glándulas Suprarrenales/patología , Paraganglioma/patología , Feocromocitoma/diagnóstico por imagen , Feocromocitoma/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Prospectivos , Cintigrafía , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
BACKGROUND: Lutetium (Lu)-177 peptide receptor radionuclide therapy (PRRT) is one of the standard treatments for somatostatin receptor-positive well-differentiated neuroendocrine tumors (NETs). However, limited Asian representation in the pivotal NETTER-1 trial and a lack of real-world data for Lu-177 PRRT from Asian regions exist. OBJECTIVE: This retrospective study aimed to evaluate the efficacy and safety of Lu-177 PRRT in Korean patients with advanced NETs. PATIENTS AND METHODS: This study analyzed 64 patients treated with Lu-177 DOTATATE PRRT at the Asan Medical Center, Seoul, Korea, between November 2019 and December 2022. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), objective response rate (ORR), and safety profile. RESULTS: The median age of patients was 55 years. Prior to PRRT, patients received a median of two lines (range 0-6) of systemic therapy. Fifty (78%) patients received the planned four cycles of Lu-177 DOTATATE PRRT. The median PFS was 21.7 months (95% confidence interval 16.7-not available) and the ORR was 20%. With a median follow-up of 15.7 months (range 1.0-39.3), the median OS was not reached and the 1-year OS rate was 88%. The median PFS was better in patients with grade 1-2 NETs than in those with grade 3 NET (not reached vs. 14.2 months; hazard ratio 3.15; p = 0.0058). Hematological toxicities were the common adverse events, including grade ≥ 3 anemia (7.8%), neutropenia (10.9%), and thrombocytopenia (9.4%). CONCLUSIONS: In Korean patients with advanced NETs, Lu-177 DOTATATE PRRT showed efficacy and safety outcomes, consistent with those in the NETTER-1 trial and previous Western real-world studies.
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Tumores Neuroendocrinos , Compuestos Organometálicos , Tomografía de Emisión de Positrones , Cintigrafía , Humanos , Persona de Mediana Edad , Lutecio , Tumores Neuroendocrinos/radioterapia , Octreótido/efectos adversos , Compuestos Organometálicos/efectos adversos , Radioisótopos , Receptores de Péptidos , República de Corea , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Rhombomeres serve to position neural progenitors in the embryonic hindbrain, thereby ensuring appropriate neural circuit formation, but the molecular identities of individual rhombomeres and the mechanism whereby they form has not been fully established. Here, we apply scMultiome analysis in zebrafish to molecularly resolve all rhombomeres for the first time. We find that rhombomeres become molecularly distinct between 10hpf (end of gastrulation) and 13hpf (early segmentation). While the embryonic hindbrain transiently contains alternating odd- versus even-type rhombomeres, our scMultiome analyses do not detect extensive odd versus even molecular characteristics in the early hindbrain. Instead, we find that each rhombomere displays a unique gene expression and chromatin profile. Prior to the appearance of distinct rhombomeres, we detect three hindbrain progenitor clusters (PHPDs) that correlate with the earliest visually observed segments in the hindbrain primordium that represent prospective rhombomere r2/r3 (possibly including r1), r4, and r5/r6, respectively. We further find that the PHPDs form in response to Fgf and RA morphogens and that individual PHPD cells co-express markers of multiple mature rhombomeres. We propose that the PHPDs contain mixed-identity progenitors and that their subdivision into individual rhombomeres requires the resolution of mixed transcription and chromatin states.
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Proteínas de Pez Cebra , Pez Cebra , Animales , Pez Cebra/genética , Estudios Prospectivos , Proteínas de Pez Cebra/metabolismo , Rombencéfalo , Cromatina/metabolismoRESUMEN
Objective: : The purpose of this finite element method (FEM) study was to analyze the biomechanical differences and tooth displacement patterns according to the traction direction, methods, and sites for total distalization of the mandibular dentition using clear aligner treatment (CAT). Methods: : A finite element analysis was performed on four FEM models using different traction methods (via a precision cut hook or button) and traction sites (mandibular canine or first premolar). A distalization force of 1.5 N was applied to the traction site by changing the direction from -30 to +30° to the occlusal plane. The initial tooth displacement and von Mises stress on the clear aligners were analyzed. Results: : All CAT-based total distalization groups showed an overall trend of clockwise or counterclockwise rotation of the occlusal plane as the force direction varied. Mesiodistal tipping of individual teeth was more prominent than that of bodily movements. The initial displacement pattern of the mandibular teeth was more predominant based on the traction site than on the traction method. The elastic deformation of clear aligners is attributed to unintentional lingual tipping or extrusion of the mandibular anterior teeth. Conclusions: : The initial tooth displacement can vary according to different distalization strategies for CAT-based total distalization. Discreet application and biomechanical understanding of traction sites and directions are necessary for appropriate mandibular total distalization.
RESUMEN
OBJECTIVES: The purpose was to identify the maxillary basal arch forms utilizing the root apices and compare the maxillary basal arch form of groups with cleft lip and palate (CLP) and normal group. MATERIALS AND METHODS: This study included 30 patients (21.8 ± 3.5 years old) with unilateral CLP (ULCP group) and 30 patients (20.9 ± 2.2 years old) with bilateral CLP (BCLP group). The normal group consisted of 30 non-cleft patients (21.2 ± 2.3 years old) with normal occlusion. Three-dimensional (3D) Cartesian coordinates of the root apices of each tooth were determined using cone-beam computed tomography. The 3D coordinates were projected onto the palatal plane to create the 2D coordinates. Thereafter, the basal arch forms were constructed by the Procrustes superimposition. Finally, For the basal arch form comparisons among groups, the inter-root widths were measured. RESULTS: Both CLP groups had a narrower inter-root width than the normal group. The BCLP group had significantly narrower premolar and molar widths than the UCLP group (P < .05). Especially, the inter-first molar width of the UCLP and BCLP groups was 3.7 ± 0.7 (P < .001) and 6.6 ± 0.8 (P < .001) mm smaller than that of the normal group, respectively. CONCLUSIONS: We used the root apices to identify the basal arch forms. The basal arch form of patients with CLP was narrower than that of the normal group. The basal arch form of patients with BCLP was narrower than that of patients with UCLP. Our findings may help clinicians better comprehend basal arch forms in patients with CLP and transverse discrepancies.