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1.
Nucl Med Commun ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39267525

RESUMEN

OBJECTIVE: Visual assessments of amyloid-ß PET, used for Alzheimer's disease (AD) diagnosis and treatment evaluation, require a careful approach when different PET ligands are utilized. Because the gray matter (GM) and white matter (WM) ligand bindings vary with age, the objective was to investigate the agreement between visual reads of 11C- and 18F-PET scans. METHODS: Cognitively unimpaired (CU) younger adults (N = 30; 39.5 ± 6.0 years), CU older adults (N = 30; 68.6 ± 5.9 years), and adults with AD (N = 22; 67.0 ± 8.5 years) underwent brain MRI, 11C-Pittsburgh compound-B (PiB)-PET, and 18F-flutemetamol-PET. Amyloid-ß deposition was assessed visually by two nuclear medicine specialists on 11C-PiB-PET and 18F-flutemetamol-PET, and quantitatively by PET centiloids. RESULTS: Seventy-two 11C-PiB-PET and 18F-flutemetamol-PET visual reads were concordant. However, 1 18F-flutemetamol-PET and 9 11C-PiB-PET were discordant with quantitative values. In four additional cases, while 11C-PiB-PET and 18F-flutemetamol-PET visual reads were concordant, both were discordant with quantitative values. Disagreements in CU younger adults were only with 11C-PiB-PET visual reads. The remaining disagreements were with CU older adults. CONCLUSION: Age, GM/WM binding, amyloid-ß load, and disease severity may affect visual assessments of PET ligands. Increase in WM binding with age causes a loss of contrast between GM and WM on 11C-PiB-PET, particularly in CU younger adults, leading to false positivity. In CU older adults, increased WM signal may bleed more into cortical regions, hiding subtle cortical uptake, especially with 18F-flutemetamol, whereas 11C-PiB can detect true regional positivity. Understanding these differences will improve patient care and treatment evaluation in clinic and clinical trials.

2.
Ann Nucl Med ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287742

RESUMEN

The gastrin-releasing peptide receptor (GRPr) has gained recognition as a promising target for both diagnostic and therapeutic applications in a variety of human cancers. This study aims to explore the primary tumor detection capabilities of [68Ga] Ga-GRPr PET imaging, specifically in newly diagnosed intra-prostatic prostate cancer lesions (PCa). Following PRISMA-DTA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies) guidelines, a systematic literature search was conducted using the Medline, Embase, Scopus, and Web of Science databases. Data regarding patient characteristics and imaging procedure details-including the type of radiotracer used, administered activity, image acquisition time, scanner modality, criteria, and detection rate of index test-were extracted from the included studies. The pooled patient-and lesion-based detection rates, along with their corresponding 95% confidence intervals (CI), were calculated using a random effects model. The final analysis included 9 studies involving 291 patients and 350 intra-prostatic lesions with [68Ga] Ga-GRPr PET imaging in primary PCa. In per-patient-based analysis of [68Ga] Ga-GRPr PET imaging, the pooled detection rates of overall and patients with Gleason score ≥ 7 were 87.09% (95% CI 74.98-93.82) and 89.01% (95% CI 68.17-96.84), respectively. In per-lesion-based analysis, the pooled detection rate [68Ga] Ga-GRPr PET imaging was 78.54% (95% CI 69.8-85.29). The pooled detection rate mpMRI (multiparametric magnetic resonance imaging) in patient-based analysis was 91.85% (95% CI 80.12-96.92). The difference between the detection rates of the mpMRI and [68Ga] Ga-GRPr PET imaging was not statistically significant (OR 0.90, 95% CI 0.23-3.51). Our findings suggest that [68Ga] Ga-GRPr PET imaging has the potential as a diagnostic target for primary PCa. Future research is needed to determine the effectiveness of [68Ga] Ga-GRPr PET in delivering additional imaging data and guiding therapeutic decisions.

3.
J Nucl Med ; 65(9): 1402-1408, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39089816

RESUMEN

Treatment with 177Lu-prostate-specific membrane antigen (PSMA)-617 (177Lu-vipivotide tetraxetan [Pluvicto]) prolongs both progression-free and overall survival in advanced PSMA-positive metastatic castration-resistant prostate cancer. Data examining specifically neurologic symptoms after 177Lu-PSMA-617 treatment are scarce. In this study, we aimed to review the neurologic findings in a large cohort of metastatic castration-resistant prostate cancer patients undergoing 177Lu-PSMA-617 therapy. Methods: The clinical records and imaging data of patients who received their initial dose of 177Lu-PSMA-617 between March 2022 and November 2022 were retrospectively reviewed. All patients presenting for medical evaluation, regardless of specific specialty appointments, with new or worsening neurologic symptoms were included in the study. Results: A total of 185 patients underwent 177Lu-PSMA-617 therapy. The median age was 70 y (range, 58-90 y). The mean follow-up time was 12.04 ± 2.87 mo. Fifty-five new or worsening neurologic symptoms were observed in 50 patients (27%, 50/185). Of these, 27 (11.9%, 27/185) reported altered taste. Eleven patients (6%, 11/185) experienced dizziness with no other clear etiology; 2 of these patients were admitted to the emergency department (ED). Paresthesia symptoms were reported in 6 patients (3.2%, 6/185). Five patients (2.7%, 5/185) reported headaches, 3 of these patients were admitted to the ED because of the severity of the symptoms. Two patients (1.08%, 2/185) presented with extremity weakness. Two patients (1.08%, 2/185) had an ischemic stroke and were admitted to the ED. One patient (0.05%, 1/185) exhibited gait disturbances. In total, 7 patients (3.78%, 7/185) were admitted to the ED because of neurologic symptoms. None of the patients discontinued or failed to complete the 177Lu-PSMA-617 therapy because of neurologic symptoms. Conclusion: After 177Lu-PSMA-617 treatment, the most common neurologic symptoms were dysgeusia and dizziness. In this study, our follow-up period and population size might not have been sufficient to detect delayed or uncommon neurologic symptoms. In patients without neurologic symptoms or central nervous system metastases before treatment, we found the development of severe neurologic problems to be rare and unlikely to require discontinuation of treatment.


Asunto(s)
Dipéptidos , Compuestos Heterocíclicos con 1 Anillo , Lutecio , Humanos , Masculino , Anciano , Persona de Mediana Edad , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/efectos adversos , Anciano de 80 o más Años , Dipéptidos/uso terapéutico , Dipéptidos/efectos adversos , Lutecio/uso terapéutico , Estudios Retrospectivos , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Neoplasias de la Próstata Resistentes a la Castración/patología , Enfermedades del Sistema Nervioso , Antígeno Prostático Específico
4.
Front Oncol ; 14: 1386718, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39070149

RESUMEN

Background: Many patients use artificial intelligence (AI) chatbots as a rapid source of health information. This raises important questions about the reliability and effectiveness of AI chatbots in delivering accurate and understandable information. Purpose: To evaluate and compare the accuracy, conciseness, and readability of responses from OpenAI ChatGPT-4 and Google Bard to patient inquiries concerning the novel 177Lu-PSMA-617 therapy for prostate cancer. Materials and methods: Two experts listed the 12 most commonly asked questions by patients on 177Lu-PSMA-617 therapy. These twelve questions were prompted to OpenAI ChatGPT-4 and Google Bard. AI-generated responses were distributed using an online survey platform (Qualtrics) and blindly rated by eight experts. The performances of the AI chatbots were evaluated and compared across three domains: accuracy, conciseness, and readability. Additionally, potential safety concerns associated with AI-generated answers were also examined. The Mann-Whitney U and chi-square tests were utilized to compare the performances of AI chatbots. Results: Eight experts participated in the survey, evaluating 12 AI-generated responses across the three domains of accuracy, conciseness, and readability, resulting in 96 assessments (12 responses x 8 experts) for each domain per chatbot. ChatGPT-4 provided more accurate answers than Bard (2.95 ± 0.671 vs 2.73 ± 0.732, p=0.027). Bard's responses had better readability than ChatGPT-4 (2.79 ± 0.408 vs 2.94 ± 0.243, p=0.003). Both ChatGPT-4 and Bard achieved comparable conciseness scores (3.14 ± 0.659 vs 3.11 ± 0.679, p=0.798). Experts categorized the AI-generated responses as incorrect or partially correct at a rate of 16.6% for ChatGPT-4 and 29.1% for Bard. Bard's answers contained significantly more misleading information than those of ChatGPT-4 (p = 0.039). Conclusion: AI chatbots have gained significant attention, and their performance is continuously improving. Nonetheless, these technologies still need further improvements to be considered reliable and credible sources for patients seeking medical information on 177Lu-PSMA-617 therapy.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38898354

RESUMEN

PURPOSE: To provide practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor (SSTR) ligands. METHODS: This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO). RESULTS: Positron emission tomography (PET) using somatostatin receptor (SSTR) ligands can detect meningioma tissue with high sensitivity and specificity and may provide clinically relevant information beyond that obtained from structural magnetic resonance imaging (MRI) or computed tomography (CT) imaging alone. SSTR-directed PET imaging can be particularly useful for differential diagnosis, delineation of meningioma extent, detection of osseous involvement, and the differentiation between posttherapeutic scar tissue and tumour recurrence. Moreover, SSTR-peptide receptor radionuclide therapy (PRRT) is an emerging investigational treatment approach for meningioma. CONCLUSION: These practice guidelines will define procedure standards for the application of PET imaging in patients with meningiomas and related SSTR-targeted PRRTs in routine practice and clinical trials and will help to harmonize data acquisition and interpretation across centers, facilitate comparability of studies, and to collect larger databases. The current document provides additional information to the evidence-based recommendations from the PET/RANO Working Group regarding the utilization of PET imaging in meningiomas Galldiks (Neuro Oncol. 2017;19(12):1576-87). The information provided should be considered in the context of local conditions and regulations.

6.
Neuro Oncol ; 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38702966

RESUMEN

Meningiomas are the most common intracranial neoplasms in adults. While most meningiomas are cured by resection, further treatment by radiotherapy may be needed, particularly in WHO grade 2 and 3 tumors which have an increased risk of recurrence, even after conventional therapies. Still, there is an urgent need for novel therapeutic strategies after exhaustion of local treatment approaches. Radionuclide therapies combine the specificity of tumor-specific antibodies or ligands with the cytotoxic activity of radioactive emitters. Alongside, integrated molecular imaging allows for a non-invasive assessment of predictive biomarkers as treatment targets. Whereas the concept of "theranostics" has initially evolved in extracranial tumors such as thyroid diseases, neuroendocrine tumors, and prostate cancer, data from retrospective case series and early phase trials underscore the potential of this strategy in meningioma. This review aims to explore the available evidence of radionuclide treatments and ongoing clinical trial initiatives in meningioma. Moreover, we discuss optimal clinical trial design and future perspectives in the field, including compound- and host-specific determinants of the efficacy of "theranostic" treatment approaches.

7.
J Nucl Med ; 65(6): 829-837, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38664015

RESUMEN

Antiamyloid therapies for Alzheimer disease recently entered clinical practice, making imaging biomarkers for Alzheimer disease even more relevant to guiding patient management. Amyloid and tau PET are valuable tools that can provide objective evidence of Alzheimer pathophysiology in living patients and will increasingly be used to complement 18F-FDG PET in the diagnostic evaluation of cognitive impairment and dementia. Parkinsonian syndromes, also common causes of dementia, can likewise be evaluated with a PET imaging biomarker,18F-DOPA, allowing in vivo assessment of the presynaptic dopaminergic neurons. Understanding the role of these PET biomarkers will help the nuclear medicine physician contribute to the appropriate diagnosis and management of patients with cognitive impairment and dementia. To successfully evaluate brain PET examinations for neurodegenerative diseases, knowledge of the necessary protocol details for obtaining a reliable imaging study, inherent limitations for each PET radiopharmaceutical, and pitfalls in image interpretation is critical. This review will focus on underlying concepts for interpreting PET examinations, important procedural details, and guidance for avoiding potential interpretive pitfalls for amyloid, tau, and dopaminergic PET examinations.


Asunto(s)
Péptidos beta-Amiloides , Dopamina , Enfermedades Neurodegenerativas , Tomografía de Emisión de Positrones , Proteínas tau , Humanos , Tomografía de Emisión de Positrones/métodos , Proteínas tau/metabolismo , Péptidos beta-Amiloides/metabolismo , Enfermedades Neurodegenerativas/diagnóstico por imagen , Enfermedades Neurodegenerativas/metabolismo , Dopamina/metabolismo , Interpretación de Imagen Asistida por Computador/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo
8.
Neuroradiol J ; : 19714009241247459, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38613202

RESUMEN

Dilated perivascular spaces (PVSs) are common and easily recognized on imaging. However, rarer giant tumefactive PVSs (GTPVSs) can have unusual multilocular cystic configurations, and are often confused for other pathologic entities, including neoplasms, cystic infarctions, and neuroepithelial cysts. Because GTPVSs are scarcely encountered and even more infrequently operated upon, many radiologists are unaware of the imaging and pathologic features of these lesions. Here, a case of a resected GTPVS is presented, highlighting both its radiologic and histologic characteristics, and discussing how such lesions can be differentiated from their closest mimickers on imaging.

9.
J Neuropathol Exp Neurol ; 83(5): 357-364, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38447592

RESUMEN

Diffuse midline glioma, H3 K27-altered (DMG-H3 K27) is an aggressive group of diffuse gliomas that predominantly occurs in pediatric patients, involves midline structures, and displays loss of H3 p.K28me3 (K27me3) expression by immunohistochemistry and characteristic genetic/epigenetic profile. Rare examples of a diffuse glioma with an H3 p.K28M (K27M) mutation and without involvement of the midline structures, so-called "diffuse hemispheric glioma with H3 p.K28M (K27M) mutation" (DHG-H3 K27), have been reported. Herein, we describe 2 additional cases of radiologically confirmed DHG-H3 K27 and summarize previously reported cases. We performed histological, immunohistochemical, molecular, and DNA methylation analysis and provided clinical follow-up in both cases. Overall, DHG-H3 K27 is an unusual group of diffuse gliomas that shows similar clinical, histopathological, genomic, and epigenetic features to DMG-H3 K27 as well as enrichment for activating alterations in MAPK pathway genes. These findings suggest that DHG-H3 K27 is closely related to DMG-H3 K27 and may represent an unusual presentation of DMG-H3 K27 without apparent midline involvement and with frequent MAPK pathway activation. Detailed reports of additional cases with clinical follow-up will be important to expand our understanding of this unusual group of diffuse gliomas and to better define the clinical outcome and how to classify DHG-H3 K27.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Niño , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Histonas/genética , Glioma/genética , Glioma/patología , Mutación/genética , Epigenómica
10.
AJNR Am J Neuroradiol ; 45(7): 971-976, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38365424

RESUMEN

BACKGROUND AND PURPOSE: Cushing disease is typically caused by a pituitary adenoma that frequently is small and challenging to detect on conventional MR imaging. High-field-strength 7T MR imaging can leverage increased SNR and contrast-to-noise ratios compared with lower-field-strength MR imaging to help identify small pituitary lesions. We aimed to describe our institutional experience with 7T MR imaging in patients with Cushing disease and perform a review of the literature. MATERIALS AND METHODS: We performed a retrospective analysis of 7T MR imaging findings in patients with pathology-proved Cushing disease from a single institution, followed by a review of the literature on 7T MR imaging for Cushing disease. RESULTS: Our institutional experience identified Cushing adenomas in 10/13 (76.9%) patients on 7T; however, only 5/13 (38.5%) lesions were discrete. Overall, the imaging protocols used were heterogeneous in terms of contrast dose as well as type of postcontrast T1-weighted sequences (dynamic, 2D versus 3D, and type of 3D sequence). From our institutional data, specific postgadolinium T1-weighted sequences were helpful in identifying a surgical lesion as follows: dynamic contrast-enhanced, 2/7 (28.6%); 2D FSE, 4/8 (50%); 3D sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE), 5/6 (83.3%); and 3D MPRAGE, 8/11 (72.7%). The literature review identified Cushing adenomas in 31/33 (93.9%) patients on 7T. CONCLUSIONS: 7T MR imaging for pituitary lesion localization in Cushing disease is a new technique with imaging protocols that vary widely. Further comparative research is needed to identify the optimal imaging technique as well as assess the benefit of 7T over lower-field-strength MR imaging.


Asunto(s)
Imagen por Resonancia Magnética , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Humanos , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adulto , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Adenoma/diagnóstico por imagen , Neoplasias Hipofisarias/diagnóstico por imagen , Anciano , Adulto Joven
11.
AJNR Am J Neuroradiol ; 45(6): 743-746, 2024 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-38290737

RESUMEN

Historically, MR imaging has been unable to detect a pituitary adenoma in up to one-half of patients with Cushing disease. This issue is problematic because the standard-of-care treatment is surgical resection, and its success is correlated with finding the tumor on imaging. Photon-counting detector CT is a recent advancement that has multiple benefits over conventional energy-integrating detector CT. We present the use of dynamic contrast-enhanced imaging using photon-counting detector CT for the detection of pituitary adenomas in patients with Cushing disease.


Asunto(s)
Adenoma , Medios de Contraste , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Neoplasias Hipofisarias , Tomografía Computarizada por Rayos X , Femenino , Humanos , Masculino , Adenoma/diagnóstico por imagen , Fotones , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico por imagen , Neoplasias Hipofisarias/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos
12.
Nat Commun ; 15(1): 493, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38216554

RESUMEN

Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B. Primary endpoint was safety and toxicity: treatment was well tolerated with no dose-limiting toxicity being observed up to the maximum feasible dose (2×107 TCID50). Median OS, a secondary endpoint, was 11.6 mo and one year survival was 45.5% comparing favorably with contemporary controls. Other secondary endpoints included assessment of viremia, MV replication and shedding, humoral and cellular immune response to the injected virus. A 22 interferon stimulated gene (ISG) diagonal linear discriminate analysis (DLDA) classification algorithm in a post-hoc analysis was found to be inversely (R = -0.6, p = 0.04) correlated with viral replication and tumor microenvironment remodeling including proinflammatory changes and CD8 + T cell infiltration in post treatment samples. This data supports that oncolytic MV derivatives warrant further clinical investigation and that an ISG-based DLDA algorithm can provide the basis for treatment personalization.


Asunto(s)
Glioblastoma , Viroterapia Oncolítica , Virus Oncolíticos , Humanos , Virus del Sarampión/genética , Antígeno Carcinoembrionario/genética , Recurrencia Local de Neoplasia/terapia , Vacuna Antisarampión , Microambiente Tumoral
13.
Clin Infect Dis ; 78(1): 80-89, 2024 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-37540989

RESUMEN

BACKGROUND: Powassan virus (POWV) is an emerging arthropod-borne flavivirus, transmitted by Ixodes spp. ticks, which has been associated with neuroinvasive disease and poor outcomes. METHODS: A retrospective study was conducted at Mayo Clinic from 2013 to 2022. We included clinical and epidemiologic data of probable and confirmed neuroinvasive POWV cases. RESULTS: Sixteen patients with neuroinvasive POWV were identified; their median age was 63.2 years, and 62.5% were male. Six patients presented with rhombencephalitis, 4 with isolated meningitis, 3 with meningoencephalitis, 2 with meningoencephalomyelitis, and 1 with opsoclonus myoclonus syndrome. A median time of 18 days was observed between symptom onset and diagnosis. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with elevated protein and normal glucose in the majority of patients. Death occurred within 90 days in 3 patients (18.8%), and residual neurologic deficits were seen in 8 survivors (72.7%). CONCLUSIONS: To our knowledge, this is the largest case series of patients with neuroinvasive POWV infection. We highlight the importance of a high clinical suspicion among patients who live in or travel to high-risk areas during the spring to fall months. Our data show high morbidity and mortality rates among patients with neuroinvasive disease.


Asunto(s)
Virus de la Encefalitis Transmitidos por Garrapatas , Encefalitis Transmitida por Garrapatas , Ixodes , Meningoencefalitis , Animales , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Encefalitis Transmitida por Garrapatas/diagnóstico , Encefalitis Transmitida por Garrapatas/epidemiología
14.
Lancet Infect Dis ; 24(3): 308-318, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38061367

RESUMEN

BACKGROUND: Despite substantial reductions in pneumococcal disease with the availability of pneumococcal conjugate vaccines, a significant burden of pneumococcal disease remains due to the diversity of serotypes combined with serotype replacement. We developed a new vaccine candidate, VAX-24 (24-valent pneumococcal conjugate vaccine), using cell-free protein synthesis to produce a variant of cross-reactive material 197 (eCRM) as the carrier protein, increasing serotype coverage while minimising carrier suppression. The aim of this clinical trial was to assess the safety, tolerability, and immunogenicity of three different doses of VAX-24 compared to pneumococcal 20-valent conjugate vaccine (PCV20). METHODS: This was a phase 1/2, randomised, double-masked study of VAX-24 versus PCV20 conducted in the USA. Key inclusion criteria included being a male or female aged 18 to 64 years in good health; key exclusion criteria included previous history of pneumococcal disease, receipt of a licensed or investigational pneumococcal vaccine, or immunosuppressive therapy. Participants were randomly allocated in a 1:1:1:1 ratio by permuted block to receive one dose of VAX-24 (1·1 µg of each antigen, 2·2 µg of each antigen, or 2·2 µg of 17 antigens mixed with 4·4 µg of seven antigens), or PCV20. The safety population included all participants with safety data. The immunogenicity population was as per-treatment in phase 2. Primary outcome measures included solicited and unsolicited adverse events. Secondary outcomes included serotype-specific opsonophagocytic activity (OPA) geometric mean titres (GMT), and IgG geometric mean concentrations (GMC) were measured 1 month postvaccination. Traditional non-inferiority criteria included OPA geometric mean ratio (GMR), with a lower bound of the two sided 95% CI of greater than 0·5 for shared serotypes. This completed trial is registered at ClinicalTrials.gov, NCT05266456. FINDINGS: Safety profiles were comparable among the treatment groups, with 170 of 209 participants (81%, 95% CI 75·2-86·2) to 178 of 207 participants (86%, 80·5-90·4) reporting at least one solicited adverse event among the three VAX-24 groups. 24 of 207 participants (12%, 7·6-16·8) to 32 of 209 of participants (15%, 10·7-20·9) experiened an unsolicited treatment emergent adverse event within 1 month postvaccination. VAX-24 2·2 µg met traditional OPA GMR non-inferiority criteria for all 20 shared serotypes; 16 serotypes elicited GMR point estimates greater than 1·0, and four reached the lower bound of the two-sided 95% CI greater than 1·0. INTERPRETATION: VAX-24 had a safety profile similar to PCV20 at all doses, with the 2·2 µg dose showing increased serotype coverage with decreased carrier suppression. FUNDING: Vaxcyte.


Asunto(s)
Infecciones Neumocócicas , Streptococcus pneumoniae , Adulto , Humanos , Masculino , Femenino , Vacunas Conjugadas , Método Doble Ciego , Anticuerpos Antibacterianos , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , Inmunogenicidad Vacunal
15.
Clin Nucl Med ; 48(11): 956-957, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37703448

RESUMEN

ABSTRACT: Leucine-rich glioma inactivated 1 autoimmune encephalitis is a treatable cause of autoimmune epilepsy associated with faciobrachial dystonic seizures-a rare form of epilepsy with frequent brief seizures primarily affecting the arm and face. We report a case with characteristic imaging findings. 18 F-FDG PET/CT demonstrated severe hypometabolism in the left basal ganglia, a regional abnormality associated with leucine-rich glioma inactivated 1 encephalitis.


Asunto(s)
Glioma , Encefalitis Límbica , Humanos , Autoanticuerpos , Leucina , Péptidos y Proteínas de Señalización Intracelular , Tomografía Computarizada por Tomografía de Emisión de Positrones/efectos adversos , Convulsiones/complicaciones , Glioma/complicaciones
16.
Atmos Environ X ; 19: 1-8, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37538994

RESUMEN

Tracer flux ratio (TFR) methodology performed downwind of 15 active oil and natural gas production sites in Ohio County, West Virginia sought to quantify air pollutant emissions over two weeks in April 2018. In coordination with a production company, sites were randomly selected depending on wind forecasts and nearby road access. Methane (CH4), ethane (C2H6), and tracer gas compounds (acetylene and nitrous oxide) were measured via tunable infrared direct absorption spectroscopy. Ion signals attributed to benzene (C6H6) and other volatile gases (e.g., C7 - C9 aromatics) were measured via proton-transfer reaction time-of-flight mass spectrometry. Short-term whole facility emission rates for 12 sites are reported. Results from TFR were systematically higher than the sum of concurrent on-site full flow sampler measurements, though not all sources were assessed on-site in most cases. In downwind plumes, the mode of the C2H6:CH4 molar ratio distribution for all sites was 0.2, which agreed with spot sample analysis from the site operator. Distribution of C6H6:CH4 ratios was skew but values between 1 and 5 pptv ppbv-1 were common. Additionally, the aromatic profile has been attributed to condensate storage tank emissions. Average ratios of C7 - C9 to C6H6 were similar to other literature values reported for natural gas wells.

17.
Marit Stud ; 22(3): 36, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37581112

RESUMEN

Although much in the lives of members of the Caiçara small-scale fishing communities of Lázaro and Saco da Ribeira in Ubatuba, southeastern Brazil would suggest hardship, that population expresses a surprising degree of satisfaction with life. In this paper, we use a social wellbeing lens as applied through an ethnographic, mixed methods approach to reflect on this overall sense that lives rooted in small-scale fishing are well worth living despite their many challenges. We see the classic maritime anthropology theme of identity at the heart of meaning and life satisfaction. Identity provides core aspects of how people engage with their realities and anchors values that are reference points in work and social relations. With reference to the relational nuances revealed by the social wellbeing perspective, however, we show that Caiçara and small-scale fishing identities are not monolithic, but reflect gender and other social positions, and personal and familial experiences. These experiences include grappling with the complex effects of economic, social, political, and environmental changes. We conclude by arguing that fisheries policy that seeks to prioritize human wellbeing would benefit by adopting a social wellbeing perspective. Fisheries policy could thereby take into account identity, values, and relational elements of social life that give meaning and a sense of belonging to small-scale fishers, while also recognizing the cross-cutting and often contradictory variations in human experience that arise from social and economic differences. This social fabric of small-scale fishers' lives shapes their intentions and actions and is thus a necessary complication to the practice of fisheries management that its proponents need to consider.

18.
Neurology ; 101(12): e1256-e1271, 2023 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-37524533

RESUMEN

BACKGROUND AND OBJECTIVES: Medulloblastomas are embryonal tumors predominantly affecting children. Recognition of molecularly defined subgroups has advanced management. Factors influencing the management and prognosis of adult patients with medulloblastoma remains poorly understood. METHODS: We examined the management, prognostic factors, and, when possible, molecular subgroup differences (subset) in adult patients (aged 18 years or older) with medulloblastoma from our center (specialty Neuro-Oncology clinic within a large academic practice) diagnosed between 1992 and 2020. Molecular subtyping corresponding to the 2021 WHO Classification was performed. Kaplan-Meier estimates (with log-rank test) were performed for univariate survival analysis with Cox regression used for multivariate analyses. RESULTS: We included 76 adult patients with medulloblastoma (62% male), with a median age of 32 years at diagnosis (range: 18-66) and median follow-up of 7.7 years (range: 0.6-27). A subset of 58 patients had molecular subgroup characterization-37 SHH-activated, 12 non-WNT/non-SHH, and 9 WNT-activated. Approximately 67% underwent gross total resection, 75% received chemotherapy at diagnosis, and 97% received craniospinal irradiation with boost. The median overall survival (OS) for the whole cohort was 14.8 years. The 2-, 5-, and 10-year OS rates were 93% (95% CI 88-99), 86% (78-94), and 64% (53-78), respectively. Survival was longer for younger patients (aged 30 years or older: 9.9 years; younger than 30 years: estimated >15.4 years; log-rank p < 0.001). There was no survival difference by molecular subgroup or extent of resection. Only age at diagnosis remained significant in multivariate survival analyses. DISCUSSION: We report one of the largest retrospective cohorts in adult patients with medulloblastoma with molecular subtyping. Survival and molecular subgroup frequencies were similar to prior reports. Survival was better for adult patients younger than 30 years at diagnosis and was not significantly different by molecular subgroup or management characteristics (extent of resection, RT characteristics, or chemotherapy timing or regimen).


Asunto(s)
Neoplasias Cerebelosas , Meduloblastoma , Niño , Humanos , Adulto , Masculino , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Femenino , Meduloblastoma/terapia , Meduloblastoma/diagnóstico , Estudios Retrospectivos , Neoplasias Cerebelosas/terapia , Neoplasias Cerebelosas/diagnóstico , Pronóstico , Análisis de Supervivencia
19.
Radiol Imaging Cancer ; 5(4): e220157, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37477566

RESUMEN

Theranostics is the combination of two approaches-diagnostics and therapeutics-applied for decades in cancer imaging using radiopharmaceuticals or paired radiopharmaceuticals to image and selectively treat various cancers. The clinical use of theranostics has increased in recent years, with U.S. Food and Drug Administration (FDA) approval of lutetium 177 (177Lu) tetraazacyclododecane tetraacetic acid octreotate (DOTATATE) and 177Lu-prostate-specific membrane antigen vector-based radionuclide therapies. The field of theranostics has imminent potential for emerging clinical applications. This article reviews critical areas of active clinical advancement in theranostics, including forthcoming clinical trials advancing FDA-approved and emerging radiopharmaceuticals, approaches to dosimetry calculations, imaging of different radionuclide therapies, expanded indications for currently used theranostic agents to treat a broader array of cancers, and emerging ideas in the field. Keywords: Molecular Imaging, Molecular Imaging-Cancer, Molecular Imaging-Clinical Translation, Molecular Imaging-Target Development, PET/CT, SPECT/CT, Radionuclide Therapy, Dosimetry, Oncology, Radiobiology © RSNA, 2023.


Asunto(s)
Neoplasias , Medicina de Precisión , Estados Unidos , Masculino , Humanos , Radiofármacos/uso terapéutico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radioisótopos/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/terapia
20.
ArXiv ; 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37396600

RESUMEN

Clinical monitoring of metastatic disease to the brain can be a laborious and timeconsuming process, especially in cases involving multiple metastases when the assessment is performed manually. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) guideline, which utilizes the unidimensional longest diameter, is commonly used in clinical and research settings to evaluate response to therapy in patients with brain metastases. However, accurate volumetric assessment of the lesion and surrounding peri-lesional edema holds significant importance in clinical decision-making and can greatly enhance outcome prediction. The unique challenge in performing segmentations of brain metastases lies in their common occurrence as small lesions. Detection and segmentation of lesions that are smaller than 10 mm in size has not demonstrated high accuracy in prior publications. The brain metastases challenge sets itself apart from previously conducted MICCAI challenges on glioma segmentation due to the significant variability in lesion size. Unlike gliomas, which tend to be larger on presentation scans, brain metastases exhibit a wide range of sizes and tend to include small lesions. We hope that the BraTS-METS dataset and challenge will advance the field of automated brain metastasis detection and segmentation.

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