scholarly journals Longitudinal pathways of cerebrospinal fluid and positron emission tomography biomarkers of amyloid-β positivity

2020 ◽  
Author(s):  
Arianna Sala ◽  
◽  
Agneta Nordberg ◽  
Elena Rodriguez-Vieitez
Keyword(s):  
Amyloid Β ◽  
Clinical Information ◽  
Alternative Pathways ◽  
Positron Emission ◽  
Risk Of Progression ◽  
Prodromal Alzheimer’S Disease ◽  
History Of ◽  
Genetic Profiles ◽  
Pet Amyloid

AbstractMismatch between CSF and PET amyloid-β biomarkers occurs in up to ≈20% of preclinical/prodromal Alzheimer’s disease individuals. Factors underlying mismatching results remain unclear. In this study we hypothesized that CSF/PET discordance provides unique biological/clinical information. To test this hypothesis, we investigated non-demented and demented participants with CSF amyloid-β42 and [18F]Florbetapir PET assessments at baseline (n = 867) and at 2-year follow-up (n = 289). Longitudinal trajectories of amyloid-β positivity were tracked simultaneously for CSF and PET biomarkers. In the longitudinal cohort (n = 289), we found that participants with normal CSF/PET amyloid-β biomarkers progressed more frequently toward CSF/PET discordance than to full CSF/PET positivity (χ2(1) = 5.40; p < 0.05). Progression to CSF+/PET+ status was ten times more frequent in cases with discordant biomarkers, as compared to csf−/pet− cases (χ2(1) = 18.86; p < 0.001). Compared to the CSF+/pet− group, the csf−/PET+ group had lower APOE-ε4ε4 prevalence (χ2(6) = 197; p < 0.001; n = 867) and slower rate of brain amyloid-β accumulation (F(3,600) = 12.76; p < 0.001; n = 608). These results demonstrate that biomarker discordance is a typical stage in the natural history of amyloid-β accumulation, with CSF or PET becoming abnormal first and not concurrently. Therefore, biomarker discordance allows for identification of individuals with elevated risk of progression toward fully abnormal amyloid-β biomarkers, with subsequent risk of neurodegeneration and cognitive decline. Our results also suggest that there are two alternative pathways (“CSF-first” vs. “PET-first”) toward established amyloid-β pathology, characterized by different genetic profiles and rates of amyloid-β accumulation. In conclusion, CSF and PET amyloid-β biomarkers provide distinct information, with potential implications for their use as biomarkers in clinical trials.

scholarly journals Oral findings during follow-up of nasopharyngeal squamous cell carcinoma treatment: A case report

2021 ◽  
Vol 9 ◽  
pp. 2050313X2110330
Author(s):  
Atsushi Musha ◽  
Nobuteru Kubo ◽  
Naoko Okano ◽  
Hidemasa Kawamura ◽  
Yuhei Miyasaka ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Nasopharyngeal Cancer ◽  
Inflammatory Conditions ◽  
Positron Emission ◽  
History Of ◽  
Oral Area

A 50-year-old woman with a long history of nasopharyngeal cancer (T2N2M0, squamous cell carcinoma) underwent chemoradiotherapy and surgery. In the past, to prevent tumor recurrence or metastasis, she underwent concurrent chemoradiotherapy or neck dissection. However, during a follow-up 10 years after the surgery, intense F-18 fluorodeoxyglucose uptake was detected in the oral area (SUVmax 6.0). A biopsy of the area with F-18 fluorodeoxyglucose uptake revealed pathological inflammation. Radiography showed the presence of a wisdom tooth, located at the F-18 fluorodeoxyglucose accumulation site, and pericoronitis of this tooth was detected. Our findings indicate the importance of considering the effect of inflammatory conditions, such as periodontal disease, in using F-18 fluorodeoxyglucose positron emission tomography/computed tomography during follow-up after head and neck cancer treatment.

The Trajectory of Cerebrospinal Fluid Growth-Associated Protein 43 in the Alzheimer’s Disease Continuum: A Longitudinal Study

2021 ◽  
pp. 1-12
Author(s):  
Heng Zhang ◽  
Diyang Lyu ◽  
Jianping Jia ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Dementia Patients ◽  
Positron Emission ◽  
Potential Biomarker ◽  
Synaptic Degeneration ◽  
Over Time

Background: Synaptic degeneration has been suggested as an early pathological event that strongly correlates with severity of dementia in Alzheimer’s disease (AD). However, changes in longitudinal cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) as a synaptic biomarker in the AD continuum remain unclear. Objective: To assess the trajectory of CSF GAP-43 with AD progression and its association with other AD hallmarks. Methods: CSF GAP-43 was analyzed in 788 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including 246 cognitively normal (CN) individuals, 415 individuals with mild cognitive impairment (MCI), and 127 with AD dementia based on cognitive assessments. The associations between a multimodal classification scheme with amyloid-β (Aβ), tau, and neurodegeneration, and changes in CSF GAP-43 over time were also analyzed. Results: CSF GAP-43 levels were increased at baseline in MCI and dementia patients, and increased significantly over time in the preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stages of AD. Higher levels of CSF GAP-43 were also associated with higher CSF phosphorylated tau (p-tau) and total tau (t-tau), cerebral amyloid deposition and hypometabolism on positron emission tomography, the hippocampus and middle temporal atrophy, and cognitive performance deterioration at baseline and follow-up. Furthermore, CSF GAP-43 may assist in effectively predicting the probability of dementia onset at 2- or 4-year follow-up. Conclusion: CSF GAP-43 can be used as a potential biomarker associated with synaptic degeneration in subjects with AD; it may also be useful for tracking the disease progression and for monitoring the effects of clinical trials.

scholarly journals Arterial thrombosis as primary presentation of endogenous Cushing’s syndrome

2019 ◽  
Vol 12 (2) ◽  
pp. bcr-2018-227491
Author(s):  
Vijay Alexander ◽  
Maria Koshy ◽  
Riddhi Dasgupta ◽  
Ronald Albert Carey
Keyword(s):  
Cushing’S Syndrome ◽  
Arterial Thrombosis ◽  
Clinical Manifestations ◽  
Dynamic Mri ◽  
Cushing's Syndrome ◽  
Positron Emission ◽  
History Of ◽  
Laboratory Investigations ◽  
Primary Presentation

Cushing’s syndrome is known to present with a characteristic set of clinical manifestations and complications, well described in literature. However, hypercoagulability remains an under recognised entity in Cushing’s syndrome. A 31-year-old woman from Southern India presented with history of fever, left upper quadrant pain and progressive breathing difficulty for 3 weeks. Clinical examination revealed discriminatory features of Cushing’s syndrome. Laboratory investigations showed biochemical features of endogenous ACTH-dependent Cushing’s syndrome. Imaging of the abdomen revealed splenic collection, left-sided empyema and extensive arterial thrombosis. Gadolinium enhanced dynamic MRI of the pituitary gland revealed no evidence of an adenoma while a Ga-68 DOTATATE positron emission tomography CT scan ruled out an ectopic Cushing’s. A diagnosis of endogenous Cushing’s syndrome causing a prothrombotic state with extensive arterial thrombosis was made. She was initiated on oral anticoagulation and oral ketoconazole for medical adrenal suppression. She subsequently underwent bilateral adrenalectomy and was well at follow-up.

Natural History of 656 Patients with Non IgM MGUS.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4860-4860
Author(s):  
Carolina Nobile ◽  
Maria T. Petrucci ◽  
Francesco Bartolozzi ◽  
Anna Levi ◽  
Marianna De Muro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Natural History ◽  
Clinical History ◽  
Cumulative Probability ◽  
Rapid Progression ◽  
Female Ratio ◽  
Predictive Parameters ◽  
Risk Of Progression ◽  
History Of

Abstract A monoclonal gammopathy of undetermined significance (MGUS) occurs in about 1% of the population over 50 years of age. Of these, about 20% evolves in Multiple Myeloma (MM); however, so far, predictive parameters of progression have not yet been identified.The aim of this study was to analyse the natural history of a cohort of non IgM MGUS and to identify whether or not there were laboratory parameters at diagnosis which can be utilized as prognostic markers of stable MGUS or progression to MM. From February 1974 to July 2001, 656 non IgM MGUS, whose clinical history was concluded (lost to follow up or died), have been followed at the Hematology of the University “La Sapienza” in Rome. The duration of follow up ranged from 2 months to 324 months, male/female ratio was 1.14, median age was 65 years (range 19–92). In each patient we evaluated: hemoglobin, platelet count, serum protein electrophoresis, serum concentration of monoclonal protein, serum calcium, creatinine, uric acid, BUN and percentage of bone marrow plasma cells.A monoclonal component (MC) of IgG type was documented in 543 patients (83%) while in 106 (16%) it was of IgA type, 6 patients had biclonal MC and 1 had a λ light chain MC; BJ proteinuria was detected in 78 (11%) patients at diagnosis. After a median follow up of 60.1 months (range 2–324) the MC remained stable in 496 patients (75%), whereas in 160 cases (25%) increased to evolve in MM. According to the literature, cumulative probability of progression to MM was 3%, 7% and 17% at 5, 10 and 15 years respectively. Differently from what observed by other investigators, in this cohort of pts, the MGUS of IgA type was not associated with a higher risk of progression to MM. The median time of progression to MM was 60.7 months (range 3–256) and factors associated with a more rapid progression to MM were advanced age and a higher number of bone marrow plasmacells. At diagnosis of MM, the concentration of the serum MC was significantly higher (P<0.003) in patients who evolved from MGUS than in those with a newly diagnosed MM. None of the studied parameters at diagnosis of MGUS were predictive of evolution to MM even though, levels of MC <2.4 g/dl and bone marrow plasmacell infiltration <9% indicated a slower progression to overt MM.

scholarly journals Emerging patterns in clonal haematopoiesis

2019 ◽  
Vol 72 (7) ◽  
pp. 453-459
Author(s):  
Jose-Mario Capo-Chichi ◽  
Phillip Michaels ◽  
Rosemarie Tremblay-Le May ◽  
Sagi Abelson ◽  
Robert Paul Hasserjian ◽  
...  
Keyword(s):  
Immune Status ◽  
Gene Mutations ◽  
Clinical Implications ◽  
Fourth Edition ◽  
Elderly Individuals ◽  
Haematopoietic Cells ◽  
Disease Biology ◽  
History Of ◽  
Genetic Profiles

Clonal haematopoiesis (CH) is defined by the presence of acquired mutations and/or cytogenetic abnormalities in haematopoietic cells. By definition, these premalignant clones do not meet criteria for haematopoietic neoplasms listed in the Revised Fourth Edition of the WHO classification. CH is fairly common in elderly individuals and is associated with higher risks for haematological cancers, in particular myelodysplastic syndrome and acute myeloid leukaemia (AML), as well as cardiovascular events. Similar small clones have also been detected during follow-up in patients with AML in morphological remission, in individuals with aplastic anaemia, and in pre-chemotherapy blood samples from patients with other types of cancers. In each of these contexts, the presence of mutations carries different clinical implications, and sometimes demonstrates unique genetic profiles. Emerging research suggests that the number and identity of mutations, the size of the mutant clones and various other factors, including age, immune status and history of exogenous drugs/toxins, are important for disease biology and progression. This review focuses specifically on the subset of CH with gene mutations detected by sequencing, and includes discussions of nomenclature and molecular technologies that detect and quantify gene mutations.

Long Term Follow-Up of 198 IgM Monoclonal Gammopathy of Undetermined Significance (MGUS).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4859-4859
Author(s):  
Ombretta Annibali ◽  
Maria T. Petrucci ◽  
Francesco Bartolozzi ◽  
Anna Levi ◽  
Patrizia Del Bianco ◽  
...  
Keyword(s):  
Lymphoproliferative Disorder ◽  
Lymphocytic Leukaemia ◽  
Great Majority ◽  
Lymphoproliferative Disease ◽  
Non Hodgkin Lymphoma ◽  
Risk Of Progression ◽  
Long Term Follow Up ◽  
History Of

Abstract MGUS is found in more than 1 % of people 50 years or older and in approximately 3% of those older than 70 years. Of these the great majority are of IgG or IgA type while IgM MGUS are less frequent.The aim of this study was to analyse the natural history of IgM MGUS and the risk of progression to lymphoproliferative disorders. From July 1973 to June 2004, we observed 323 monoclonal gammopathies of IgM type. At diagnosis, 198 (61%) were MGUS, 111 (34%) were Waldeström’s Macroglobulinemia (WM) of whom 11 were pretreated, 8 (2,4%) were non Hodgkin Lymphoma (NHL), 5 (1,5%) were IgM Myeloma and only 1 was a chronic lymphocytic leukaemia. Of 198 patients with IgM MGUS, 125 (63%) were men and 73 (37%) were women ( ratio 1.71).Median age at diagnosis was 65.7 (range 33–89 years). At diagnosis, all patients had an IgM concentration less than 2 gr/dl with a median of 1.7 g/dl. Median Hb, serum creatinine and albumin levels were: 13.2 gr/dl, (range 6.9–17.9), 1,04 mg/dl ( range 0.6– 2,5) and 3.9 gr/dl ( range 2.4–5). Hepatomegaly as well as splenomegaly were present in 24% and 14% of patients, respectively. The 198 patients were monitored for 8741 months/person (median 25 months, range 0–411). During The follow up a lymphoproliferative disorder developed in 17 (8.5%) patients. In particular 11 pts (5.5%) pts evolved to WM and 6 (3%) to NHL. Progression incidence to linfoproliferative disorders was 0.001 months/person. Cumulative incidence of progression to lymphoproliferative disease was 1.3 % at 1 years, 6.8 % at 5 years, 23.2% at 10 years and 45.4% at 15 years. In conclusion the patients with IgM MGUS are more likely to die of unrelated diseases than to have progression to a malignant lymphoproliferative disorder.

scholarly journals Identification of patients who will not achieve seizure remission within 5 years on AEDs

Neurology ◽  
2018 ◽  
Vol 91 (22) ◽  
pp. e2035-e2044 ◽  
Author(s):  
David M. Hughes ◽  
Laura J. Bonnett ◽  
Gabriela Czanner ◽  
Arnošt Komárek ◽  
Anthony G. Marson ◽  
...  
Keyword(s):  
External Validation ◽  
Clinical Information ◽  
Patient Counseling ◽  
Degree Relative ◽  
History Of ◽  
Similar Accuracy ◽  
Patient’S History ◽  
Patients With Epilepsy ◽  
Baseline Covariates

ObjectiveTo identify people with epilepsy who will not achieve a 12-month seizure remission within 5 years of starting treatment.MethodsThe Standard and New Antiepileptic Drug (SANAD) study is the largest prospective study in patients with epilepsy to date. We applied a recently developed multivariable approach to the SANAD dataset that takes into account not only baseline covariates describing a patient's history before diagnosis but also follow-up data as predictor variables.ResultsChanges in number of seizures and treatment history were the most informative time-dependent predictors and were associated with history of neurologic insult, epilepsy type, age at start of treatment, sex, and having a first-degree relative with epilepsy. Our model classified 95% of patients. Of those classified, 95% of patients observed not to achieve remission at 5 years were correctly classified (95% confidence interval [CI] 89.5%–100%), with 51% identified by 3 years and 90% within 4 years of follow-up. Ninety-seven percent (95% CI 93.3%–98.8%) of patients observed to achieve a remission within 5 years were correctly classified. Of those predicted not to achieve remission, 76% (95% CI 58.5%–88.2%) truly did not achieve remission (positive predictive value). The predictive model achieved similar accuracy levels via external validation in 2 independent United Kingdom–based datasets.ConclusionOur approach generates up-to-date predictions of the patient's risk of not achieving seizure remission whenever new clinical information becomes available that could influence patient counseling and management decisions.

scholarly journals Variables Associated with Endometriosis-related Pain: A Pilot Study using a Visual Analogue Scale

2019 ◽  
Vol 41 (03) ◽  
pp. 170-175 ◽  
Author(s):  
Mauro Cozzolino ◽  
Maria Coccia ◽  
Giacomo Lazzeri ◽  
Francesca Basile ◽  
Gianmarco Troiano
Keyword(s):  
Visual Analogue Scale ◽  
Analogue Scale ◽  
Complex Disease ◽  
Smoking Habit ◽  
Clinical Information ◽  
University Hospital ◽  
History Of ◽  
Vas Scores ◽  
A Prospective Study

Objective Endometriosis is a complex disease, and pain is an important component of the syndrome. One of the most used methods to assess pain is the visual analogue scale (VAS). The aim of the present research was to study the pain experienced by patients who referred to our unit for endometriosis, using the VAS to understand the variables that could influence it. Methods We have conducted a prospective study from February 2012 to December 2016, enrolling 388 patients who referred to a university hospital, in Florence, Italy. We have included in the present study patients during their follow-up for endometriosis; we have also included patients who underwent surgery with a histological diagnosis of endometriosis. We have collected sociodemographic and clinical information regarding age, body mass index (BMI), smoking habit, number of pregnancies, and endometriosis staging. Finally, we have administered the VAS for several symptoms. Results Dysmenorrhea was the symptom associated with the highest perception of pain (mean VAS score of 5.76). The logistic regression showed that the stage of endometriosis could influence the pain associated to constipation and to dysuria. The linear regression showed that age could influence the pain associated to constipation, to dyspareunia, and to dysmenorrhea. A positive correlation was found between dysmenorrhea and chronic pelvic pain (CPP), between dysmenorrhea and dyspareunia, and between constipation and dysuria. Conclusion Using a validated method, the VAS, we have studied the pain experienced by a group of patients with a history of endometriosis and observed that smoking habit and BMI did not influence the VAS scores, and that dysmenorrhea was associated with the highest perception of pain.

scholarly journals Impact of PET/CT among patients with suspected mycotic aortic aneurysms

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258702
Author(s):  
Lars Husmann ◽  
Martin W. Huellner ◽  
Hannes Gruenig ◽  
Nadia Eberhard ◽  
Carlos A. Mestres ◽  
...  
Keyword(s):  
Patient Management ◽  
Laboratory Data ◽  
Clinical Information ◽  
Diagnostic Procedures ◽  
Health Condition ◽  
Aortic Aneurysms ◽  
Positron Emission ◽  
Pet Ct ◽  
The Impact

Purpose To determine the impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) on clinical management in patients with suspected mycotic aortic aneurysms (MAA). Materials and methods For this observational cohort study 101 PET/CT were acquired in 50 patients, thereof 50 for the initial diagnosis/baseline scan, 51 for follow-up. Impact on patient management was defined in three categories: PET/CT results were “confirmed” (by clinical follow-up), “suspected” (conclusive, not confirmed), or “misleading” (proven wrong by follow-up). For clinical follow-up patient data were recorded at the time of imaging, and at the latest recorded clinical visit. It included patient demographics, clinical information, laboratory data, results of microbiology and other diagnostic procedures, information about treatment, and patient’s general health condition. Results In four patients (8%) no clinical follow-up was feasible, the other 46 patients were clinically followed for a median of 898 days (IQR 320–4105). The combined evaluation of all 101 PET/CT demonstrated an impact on patient management in 78,5% of cases (48,5% confirmed, 30% suspected). Results of 21,5% of the PET/CT examinations were misleading. Respective values at baseline and at follow-up were: impact on patient management in 82% and 74,5% (70% and 27.5% confirmed, and 12% and 47% suspected), misleading cases in 18% and 25.5%. Conclusion In MAA, PET/CT has a high impact on patient management, which is more pronounced with baseline than with follow-up examinations. However, PET/CT results may be misleading in a smaller proportion of cases.

Sign in / Sign up

Export Citation Format

Share Document