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European Heart Journal. Case Reports Apr 2024Desmoplakin cardiomyopathy has been recently classified as a non-dilated left ventricular cardiomyopathy, which is characterized by inflammatory-like episodes followed...
BACKGROUND
Desmoplakin cardiomyopathy has been recently classified as a non-dilated left ventricular cardiomyopathy, which is characterized by inflammatory-like episodes followed by left ventricular fibrosis/dysfunction and ventricular arrhythmias. Specific management is unclear.
CASE SUMMARY
We report a detailed case of a 46-year-old Caucasian woman presenting with repeated sudden cardiac arrests who was diagnosed with a new variant in the desmoplakin gene. Because the initial 18F-fluorodeoxyglucose positron emission tomography scan showed significant hypermetabolism, she was treated with immunosuppressors, with only minimal improvement on imaging.
DISCUSSION
Desmoplakin cardiomyopathy should be considered in the differential diagnosis of inflammatory cardiomyopathies. Little is known about the use of immunosuppressive treatments, but it could be reasonable for some selected patients.
PubMed: 38887779
DOI: 10.1093/ehjcr/ytae160 -
Cureus May 2024Febrile infection-related epilepsy syndrome (FIRES) is a rare epileptic encephalopathy that occurs in children or adolescents. To date, evidence for the management of...
Febrile infection-related epilepsy syndrome (FIRES) is a rare epileptic encephalopathy that occurs in children or adolescents. To date, evidence for the management of the post-acute phase of FIRES is focused on drug-resistant epilepsy that continues from the acute phase. Information on involuntary movements, which are newly developed in the chronic phase, is limited. We report a 13-year-old boy, who had a history of FIRES at nine years of age and experienced worsening seizure control that was accompanied by unremitting involuntary movements after two years of a fairly controlled period. The involuntary movements resulted in motor deterioration and forced him to be bedridden. Although no neuronal autoantibodies were detected, we hypothesized that the boy's neurological deterioration was triggered by an autoimmune response based on the elevation of serum anti-glutamic acid decarboxylase and serum anti-thyroid peroxidase antibodies and hypermetabolism of bilateral lenticular nuclei on 18-fluorodeoxyglucose positron emission tomography that resembled those reported in patients with other types of autoimmune encephalitis. Serial methylprednisolone pulse therapy and intravenous immunoglobulin therapy ameliorated involuntary movements and improved his activities of daily living. Late-onset involuntary movements, along with seizure exacerbation, may appear in the chronic phase of FIRES. Immunotherapy could be effective in treating these symptoms.
PubMed: 38887352
DOI: 10.7759/cureus.60525 -
Frontiers in Endocrinology 2024This study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of F-AlF-NOTA-octreotide (F-OC)... (Review)
Review
INTRODUCTION
This study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of F-AlF-NOTA-octreotide (F-OC) positron emission tomography/computed tomography (PET/CT).
METHODS
We analyzed TIO patients who underwent F-OC PET/CT. Parameters such as tumor dimension, the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean) and metabolic tumor volume (MTV) were meticulously assessed. Clinical features and imaging characteristics pertinent to TIO were reviewed.
RESULTS
6 patients with clinical suspicion of TIO exhibited hypophosphatemia (0.25 to 0.64 mmol/L), elevated alkaline phosphatase (ALP) levels (142 to 506 U/L), and increased parathyroid hormone (PTH) levels (92.9 to 281.7 pg/mL). Of these patients, two underwent FGF-23 testing, with results of 3185.00 pg/ml and 17.56 pg/ml, respectively. Conventional imaging modalities depicted widespread osteoporosis, with several cases demonstrating fractures indicative of osteomalacic and associated pathological fractures. Subsequent F-OC PET/CT facilitated the accurate localization of causative tumors, with histopathological examination confirming the diagnosis of phosphaturic mesenchymal tumor (PMT). The interval from initial clinical presentation to definitive TIO diagnosis spanned approximately 2.5 years (range: 1 - 4 years), with tumors varying in size (maximum diameter: 7.8 to 40.0 mm), SUVmax (5.47 to 25.69), SUVmean (3.43 to 7.26), and MTV (1.27 to 18.59 cm).
CONCLUSION
The implementation of whole-body F-OC PET/CT imaging emerges as a critical tool in the identification of occult tumors causing TIO. Future investigations incorporating a broader cohort are imperative to further delineate the diagnostic and therapeutic implications of F-OC PET/CT in managing TIO.
Topics: Humans; Fibroblast Growth Factor-23; Fluorine Radioisotopes; Heterocyclic Compounds; Heterocyclic Compounds, 1-Ring; Neoplasms, Connective Tissue; Octreotide; Osteomalacia; Paraneoplastic Syndromes; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals
PubMed: 38887276
DOI: 10.3389/fendo.2024.1400751 -
Alzheimer's Research & Therapy Jun 2024There is good evidence that elevated amyloid-β (Aβ) positron emission tomography (PET) signal is associated with cognitive decline in clinically normal (CN)...
BACKGROUND
There is good evidence that elevated amyloid-β (Aβ) positron emission tomography (PET) signal is associated with cognitive decline in clinically normal (CN) individuals. However, it is less well established whether there is an association between the Aβ burden and decline in daily living activities in this population. Moreover, Aβ-PET Centiloids (CL) thresholds that can optimally predict functional decline have not yet been established.
METHODS
Cross-sectional and longitudinal analyses over a mean three-year timeframe were performed on the European amyloid-PET imaging AMYPAD-PNHS dataset that phenotypes 1260 individuals, including 1032 CN individuals and 228 participants with questionable functional impairment. Amyloid-PET was assessed continuously on the Centiloid (CL) scale and using Aβ groups (CL < 12 = Aβ-, 12 ≤ CL ≤ 50 = Aβ-intermediate/Aβ± , CL > 50 = Aβ+). Functional abilities were longitudinally assessed using the Clinical Dementia Rating (Global-CDR, CDR-SOB) and the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q). The Global-CDR was available for the 1260 participants at baseline, while baseline CDR-SOB and A-IADL-Q scores and longitudinal functional data were available for different subsamples that had similar characteristics to those of the entire sample.
RESULTS
Participants included 765 Aβ- (61%, Mdn = 66.0, IQR = 61.0-71.0; 59% women), 301 Aβ± (24%; Mdn = 69.0, IQR = 64.0-75.0; 53% women) and 194 Aβ+ individuals (15%, Mdn = 73.0, IQR = 68.0-78.0; 53% women). Cross-sectionally, CL values were associated with CDR outcomes. Longitudinally, baseline CL values predicted prospective changes in the CDR-SOB (b = 0.001/CL/year, 95% CI [0.0005,0.0024], p = .003) and A-IADL-Q (b = -0.010/CL/year, 95% CI [-0.016,-0.004], p = .002) scores in initially CN participants. Increased clinical progression (Global-CDR > 0) was mainly observed in Aβ+ CN individuals (HR = 2.55, 95% CI [1.16,5.60], p = .020). Optimal thresholds for predicting decline were found at 41 CL using the CDR-SOB (b = 0.137/year, 95% CI [0.069,0.206], p < .001) and 28 CL using the A-IADL-Q (b = -0.693/year, 95% CI [-1.179,-0.208], p = .005).
CONCLUSIONS
Amyloid-PET quantification supports the identification of CN individuals at risk of functional decline.
TRIAL REGISTRATION
The AMYPAD PNHS is registered at www.clinicaltrialsregister.eu with the EudraCT Number: 2018-002277-22.
Topics: Humans; Positron-Emission Tomography; Female; Male; Cross-Sectional Studies; Longitudinal Studies; Aged; Amyloid beta-Peptides; Activities of Daily Living; Cognitive Dysfunction; Middle Aged; Brain; Aged, 80 and over
PubMed: 38886831
DOI: 10.1186/s13195-024-01494-9 -
Alzheimer's Research & Therapy Jun 2024Autopsy work indicates that the widely-projecting noradrenergic pontine locus coeruleus (LC) is among the earliest regions to accumulate hyperphosphorylated tau, a...
BACKGROUND
Autopsy work indicates that the widely-projecting noradrenergic pontine locus coeruleus (LC) is among the earliest regions to accumulate hyperphosphorylated tau, a neuropathological Alzheimer's disease (AD) hallmark. This early tau deposition is accompanied by a reduced density of LC projections and a reduction of norepinephrine's neuroprotective effects, potentially compromising the neuronal integrity of LC's cortical targets. Previous studies suggest that lower magnetic resonance imaging (MRI)-derived LC integrity may signal cortical tissue degeneration in cognitively healthy, older individuals. However, whether these observations are driven by underlying AD pathology remains unknown. To that end, we examined potential effect modifications by cortical beta-amyloid and tau pathology on the association between in vivo LC integrity, as quantified by LC MRI signal intensity, and cortical neurodegeneration, as indexed by cortical thickness.
METHODS
A total of 165 older individuals (74.24 ± 9.72 years, ~ 60% female, 10% cognitively impaired) underwent whole-brain and dedicated LC 3T-MRI, Pittsburgh Compound-B (PiB, beta-amyloid) and Flortaucipir (FTP, tau) positron emission tomography. Linear regression analyses with bootstrapped standard errors (n = 2000) assessed associations between bilateral cortical thickness and i) LC MRI signal intensity and, ii) LC MRI signal intensity interacted with cortical FTP or PiB (i.e., EC FTP, IT FTP, neocortical PiB) in the entire sample and a low beta-amyloid subsample.
RESULTS
Across the entire sample, we found a direct effect, where lower LC MRI signal intensity was associated with lower mediolateral temporal cortical thickness. Evaluation of potential effect modifications by FTP or PiB revealed that lower LC MRI signal intensity was related to lower cortical thickness, particularly in individuals with elevated (EC, IT) FTP or (neocortical) PiB. The latter result was present starting from subthreshold PiB values. In low PiB individuals, lower LC MRI signal intensity was related to lower EC cortical thickness in the context of elevated EC FTP.
CONCLUSIONS
Our findings suggest that LC-related cortical neurodegeneration patterns in older individuals correspond to regions representing early Braak stages and may reflect a combination of LC projection density loss and emergence of cortical AD pathology. This provides a novel understanding that LC-related cortical neurodegeneration may signal downstream consequences of AD-related pathology, rather than being exclusively a result of aging.
Topics: Humans; Locus Coeruleus; Female; Alzheimer Disease; Male; Aged; Magnetic Resonance Imaging; tau Proteins; Aged, 80 and over; Cohort Studies; Amyloid beta-Peptides; Positron-Emission Tomography; Cerebral Cortex; Carbolines; Thiazoles; Aniline Compounds; Brain Cortical Thickness
PubMed: 38886798
DOI: 10.1186/s13195-024-01500-0 -
Scientific Reports Jun 2024Tumor-to-normal ratio (T/N) measurement of F-FBPA is crucial for patient eligibility to receive boron neutron capture therapy. This study aims to compare the difference... (Comparative Study)
Comparative Study
Tumor-to-normal ratio (T/N) measurement of F-FBPA is crucial for patient eligibility to receive boron neutron capture therapy. This study aims to compare the difference in standard uptake value ratios on brain tumors and normal brains using PET/MR ZTE and atlas-based attenuation correction with the current standard PET/CT attenuation correction. Regarding the normal brain uptake, the difference was not significant between PET/CT and PET/MR attenuation correction methods. The T/N ratio of PET/CT-AC, PET/MR ZTE-AC and PET/MR AB-AC were 2.34 ± 0.95, 2.29 ± 0.88, and 2.19 ± 0.80, respectively. The T/N ratio comparison showed no significance using PET/CT-AC and PET/MR ZTE-AC. As for the PET/MRI AB-AC, significantly lower T/N ratio was observed (- 5.18 ± 9.52%; p < 0.05). The T/N difference between ZTE-AC and AB-AC was also significant (4.71 ± 5.80%; p < 0.01). Our findings suggested PET/MRI imaging using ZTE-AC provided superior quantification on F-FBPA-PET compared to atlas-based AC. Using ZTE-AC on F-FBPA-PET /MRI might be crucial for BNCT pre-treatment planning.
Topics: Humans; Boron Neutron Capture Therapy; Brain Neoplasms; Female; Male; Magnetic Resonance Imaging; Positron Emission Tomography Computed Tomography; Middle Aged; Positron-Emission Tomography; Adult; Aged; Brain; Fluorine Radioisotopes; Boron Compounds; Phenylalanine
PubMed: 38886395
DOI: 10.1038/s41598-024-63248-9 -
Surgical Case Reports Jun 2024Despite the recent developments in the treatment of advanced or recurrent gastric cancer, the median survival time remains shorter than 15 months. Herein, we report a...
BACKGROUND
Despite the recent developments in the treatment of advanced or recurrent gastric cancer, the median survival time remains shorter than 15 months. Herein, we report a case of postoperative gastric cancer recurrence in which a complete clinical response was achieved with trastuzumab deruxtecan as 6th-line treatment.
CASE PRESENTATION
A 70-year-old man underwent abdominal contrast-enhanced computed tomography (CT) during follow-up after rectal cancer surgery. The CT revealed an enlarged perigastric lymph node. After further examination, the patient's condition was diagnosed as gastric cancer cT2N1H0P0M0 cStage IIA. The patient underwent distal gastrectomy and D2 lymph node dissection. The resulting pathological diagnosis was pT1bN3aH0P0 pStageIIB, HER2 score 3+. Abdominal contrast-enhanced CT 19 months postoperatively revealed para-aortic lymph node recurrence, thus systemic chemotherapy courses were planned. The primary treatment was a combination of S-1, cisplatin, and trastuzumab administered in 11 courses. However, there was an enlargement of the para-aortic lymph node which was evaluated as progressive disease. Systematic chemotherapy with various regimens was continued until the 5th-line treatment. However, therapeutic benefits were not achieved and lung metastasis was observed. Trastuzumab deruxtecan (TDXD) was initiated as 6th-line treatment. Abdominal contrast-enhanced CT at 4 months after the start of treatment showed marked shrinkage of the enlarged para-aortic lymph node and disappearance of the lung metastasis in the right upper lung lobe, which was evaluated as partial response (PR). The para-aortic lymph node metastasis was evaluated as PR with only a slight accumulation of SUV-Max 2.66 with a shrinking trend by positron emission tomography-computed tomography (PET-CT) performed after 1 year. Tumor markers CEA, CA19-9, and CA125 also improved significantly. PET-CT after 1 year and 4 months showed no lymph node enlargement or accumulation, indicating a complete response (CR). All tumor markers also normalized. The patient has maintained clinical CR without additional treatment to date.
CONCLUSIONS
We report the apparent first case of postoperative gastric cancer recurrence successfully treated with TDXD, achieving clinical CR with TDXD as a 6th-line treatment.
PubMed: 38886285
DOI: 10.1186/s40792-024-01954-2 -
Journal For Immunotherapy of Cancer Jun 2024Immune checkpoint inhibitors (ICIs) can elicit anticancer immune responses, but predictive biomarkers are needed. We measured programmed death ligand 1 (PD-L1)...
Exploring the predictive potential of programmed death ligand 1 expression in healthy organs and lymph nodes as measured by F-BMS986-192 PET: pooled analysis of data from four solid tumor types.
INTRODUCTION
Immune checkpoint inhibitors (ICIs) can elicit anticancer immune responses, but predictive biomarkers are needed. We measured programmed death ligand 1 (PD-L1) expression in organs and lymph nodes using F-BMS-986192 positron emission tomography (PET)-imaging and looked for correlations with response and immune-related adverse events.
METHODS
Four F-BMS-986192 PET studies in patients with melanoma, lung, pancreatic and oral cancer, receiving ICI treatment, were combined. Imaging data (organ standardized uptake value (SUV), lymph node SUV) and clinical data (response to treatment and incidence of immune-related adverse events) were extracted.
RESULTS
Baseline PD-L1 uptake in the spleen was on average higher in non-responding patients than in responders (spleen SUV 16.1±4.4 vs 12.5±3.4, p=0.02). This effect was strongest in lung cancer, and not observed in oral cancer. In the oral cancer cohort, benign tumor-draining lymph nodes (TDLNs) had higher PD-L1 uptake (SUV 3.3 IQR 2.5-3.9) compared with non-TDLNs (SUV 1.8, IQR 1.4-2.8 p=0.04). Furthermore, in the same cohort non-responders showed an increase in PD-L1 uptake in benign TDLNs on-treatment with ICIs (+15%), while for responders the PD-L1 uptake decreased (-11%). PD-L1 uptake did not predict immune-related adverse events, though elevated thyroid uptake on-treatment correlated with pre-existing thyroid disease or toxicity.
CONCLUSION
PD-L1 PET uptake in the spleen is a potential negative predictor of response to ICIs. On-treatment with ICIs, PD-L1 uptake in benign TDLNs increases in non-responders, while it decreases in responders, potentially indicating a mechanism for resistance to ICIs in patients with oral cancer.
Topics: Humans; B7-H1 Antigen; Lymph Nodes; Positron-Emission Tomography; Male; Female; Neoplasms; Immune Checkpoint Inhibitors; Middle Aged; Aged
PubMed: 38886117
DOI: 10.1136/jitc-2024-008899 -
Neurology(R) Neuroimmunology &... Jul 2024Kleine-Levin syndrome (KLS) is a rare recurrent hypersomnolence disorder associated with cognitive and behavioral disturbances, of unknown origin, but inflammatory...
OBJECTIVES
Kleine-Levin syndrome (KLS) is a rare recurrent hypersomnolence disorder associated with cognitive and behavioral disturbances, of unknown origin, but inflammatory mechanisms could be involved. We aimed to explore in vivo microglia activation using [F]DPA-714 PET imaging in patients with KLS compared with controls, and during symptomatic vs asymptomatic periods.
METHODS
Patients with KLS and controls underwent a standardized clinical evaluation and PET imaging, using a radiolabeled ligand specific to the 18 kDa translocator protein. Images were processed on the PMOD (peripheral module) interface using a standard uptake value (SUV). Five regions of interest (ROIs) were analyzed: hypothalamus, thalamus, frontal area, cerebellum, and whole brain. SUV ratios (SUVr) were calculated by normalizing SUV with cerebellum uptake.
RESULTS
Images of 17 consecutive patients with KLS (7 during episodes, 10 out of episodes) and 14 controls were analyzed. We found no SUV/SUVr difference between KLS and controls, between patients in and out episodes in all ROIs, and no correlation between SUVr and episode duration at the time of PET scan. No association was found between SUVr and sex, disease duration, or orexin levels.
DISCUSSION
Our findings do not support the presence of neuroinflammation in KLS. Further research is needed to identify relevant biomarkers in KLS.
Topics: Humans; Kleine-Levin Syndrome; Male; Positron-Emission Tomography; Female; Microglia; Adult; Young Adult; Adolescent; Brain; Middle Aged
PubMed: 38885456
DOI: 10.1212/NXI.0000000000200263 -
EJNMMI Research Jun 2024In preclinical studies, the positron emission tomography (PET) imaging with [C]UCB-A provided promising results for imaging synaptic vesicle protein 2A (SV2A) as a proxy...
BACKGROUND
In preclinical studies, the positron emission tomography (PET) imaging with [C]UCB-A provided promising results for imaging synaptic vesicle protein 2A (SV2A) as a proxy for synaptic density. This paper reports the first-in-human [C]UCB-A PET study to characterise its kinetics in healthy subjects and further evaluate SV2A-specific binding.
RESULTS
Twelve healthy subjects underwent 90-min baseline [C]UCB-A scans with PET/MRI, with two subjects participating in an additional blocking scan with the same scanning procedure after a single dose of levetiracetam (1500 mg). Our results indicated abundant [C]UCB-A brain uptake across all cortical regions, with slow elimination. Kinetic modelling of [C]UCB-A PET using various compartment models suggested that the irreversible two-tissue compartment model best describes the kinetics of the radioactive tracer. Accordingly, the Patlak graphical analysis was used to simplify the analysis. The estimated SV2A occupancy determined by the Lassen plot was around 66%. Significant specific binding at baseline and comparable binding reduction as grey matter precludes the use of centrum semiovale as reference tissue.
CONCLUSIONS
[C]UCB-A PET imaging enables quantifying SV2A in vivo. However, its slow kinetics require a long scan duration, which is impractical with the short half-life of carbon-11. Consequently, the slow kinetics and complicated quantification methods may restrict its use in humans.
PubMed: 38884834
DOI: 10.1186/s13550-024-01117-2