The role of cerebrospinal fluid (CSF) biomarkers, and neuroimaging in the diagnostic process of Alzheimer's disease (AD) is not clear, in particular in the older patients.
The aim of this study was ...to compare the clinical diagnosis of AD with CSF biomarkers and with cerebrovascular damage at neuroimaging in a cohort of geriatric patients.
Retrospective analysis of medical records of ≥65-year-old patients with cognitive impairment referred to an Italian geriatric outpatient clinic, for whom the CSF concentration of amyloid-β (Aβ), total Tau (Tau), and phosphorylated Tau (p-Tau) was available. Clinical diagnosis (no dementia, possible and probable AD) was based on the following two sets of criteria: (1) the
(
-IV) plus the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and (2) the National Institute on Aging-Alzheimer's Association (NIA-AA). The Fazekas visual scale was applied when a magnetic resonance imaging scan was available.
We included 94 patients, mean age 77.7 years, mean Mini Mental State Examination score 23.9. The concordance (kappa coefficient) between the two sets of clinical criteria was 70%. The mean CSF concentration (pg/ml) (±SD) of biomarkers was as follows: Aβ 687 (±318), Tau 492 (±515), and p-Tau 63 (±56). There was a trend for lower Aβ and higher Tau levels from the no dementia to the probable AD group. The percentage of
according to the local cutoffs was still 15 and 21% in patients without AD based on the
-IV plus NINCDS-ADRDA or the NIA-AA criteria, respectively. The exclusion of patient in whom normotensive hydrocephalus was suspected did not change these findings. A total of 80% of patients had the neuroimaging report describing chronic cerebrovascular damage, while the Fazekas scale was positive in 45% of patients overall, in 1/2 of no dementia or possible AD patients, and in about 1/3 of probable AD patients, with no difference across ages.
We confirmed the expected discrepancy between different approaches to the diagnosis of AD in a geriatric cohort of patients with cognitive impairment. Further research is needed to understand how to interpret this discrepancy and provide clinicians with practical guidelines.
Confabulation may be present in Alzheimer's disease (AD), but usually it is not a primary feature of either its typical or atypical variants. In this report, we describe the case of an AD patient who ...showed an unusual and enduring neuropsychiatric phenotype characterized by early and prominent spontaneous confabulation. Surprisingly, such atypical AD presentation bears a striking resemblance to presbyophrenia, a subtype of dementia which was described at the beginning of the twentieth century and then sank into oblivion. In discussion, we speculate on the "return" of presbyophrenia as an unrecognized neuropsychiatric variant of AD and its possible neuroanatomical substrates.
Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough ...infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection.
COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine, autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected.
After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level.
LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level.
We describe a case of late onset frontotemporal dementia carrying the g.1977_1980 delCACT (Thr272fs) mutation in progranulin (GRN) gene, characterized by a positive family history for dementia and a ...clinical phenotype resembling dementia with Lewy bodies. Symptoms included prominent visuospatial impairment, complex misidentification syndrome, visual zooptic hallucinations, hypersomnia, mental fluctuations, and signs of parkinsonism. The patient showed normal cerebrospinal fluid levels of amyloid-β, tau, and Ptau biomarkers, an asymmetric pattern of cerebral atrophy and hypoperfusion, and parietal hypometabolism. A major contributing factor to the diagnosis was the testing of plasmatic progranulin levels (extremely low), which prompted us to sequence GRN.
PURPOSEThe aim of this study was to assess the relationship between administered Tc tetrofosmin activity in myocardial gated-SPECT and findings of myocardial perfusion and left ventricular ejection ...fraction (LVEF) as markers of diagnostic outcome.
MATERIALS AND METHODSFifty-two patients with heterogeneous cardiac diseases and a clinical referral for myocardial perfusion imaging were prospectively studied. A separate-day acquisition protocol was adopted with a low fixed activity of 370 MBq, which corresponds to an average reduction of 31% with respect to the median value of 533 MBq usually administered in our laboratory. A standard acquisition with a time/frame of 25 seconds was performed (ST). Immediately after the conclusion of the first acquisition, a second acquisition was performed with a high time/frame of 33 seconds (HT), which corresponds to an increase of 31% with respect to standard time/frame adopted in our laboratory. The order of ST and HT acquisitions was randomized in individual patients. The summed stress scores (SSS), the summed rest scores (SRS), the LVEF, and the end-diastolic volume (EDV) were automatically calculated.
RESULTSThe image quality score was significantly higher in HT than in ST. No significant differences were found in SSS, SRS, LVEF, and EDV between HT and ST SPECT. The agreement between HT and ST was 84% (kw = 0.88) in the correct classification of stress images. The agreement between HT and ST was 84% (k = 0.70) in the detection of ischemia and scar. The limits of agreement between the HT and the ST methods were roughly within ±3 points for SSS and SRS, ±13% for poststress LVEF, and ±18 mL for poststress EDV.
CONCLUSIONSUsing about half of the activity recommended by the current diagnostic reference levels for separate-day myocardial perfusion imaging, the present study demonstrates that images may be obtained using ST protocol with quantitative results comparable with those from studies performed using the HT protocol, which is equivalent to an administered activity of 530 MBq. The former protocol would allow for a significant reduction of the dose to the patients as well as to the operators. Further studies are needed to confirm that this dose-sparing approach does not hamper sensitivity and specificity for coronary stenoses.
Summary Background Gas6 protein is involved in pulmonary embolism (PE) and acute inflammation in animal models. Methods We enrolled 82 consecutive patients with acute dyspnea and suspected PE (Geneva ...score with high (HCP) or low/intermediate clinical probability (LICP) + D-dimer ≥0.5 μg/mL) and 29 age-matched healthy volunteers. According to clinical and instrumental evaluations the following diagnoses were obtained: heart failure (HF), pulmonary or systemic infection (I), PE, or no illness (N). Twenty-two patients were excluded due to oral anticoagulation (9), lack of CT angiography or pulmonary scintigraphy (6), plasma creatinine ≥3 mg/dL (3), and pulmonary cancer (4). Plasma Gas6 was measured with a validated enzyme-linked immunoassay. Non-parametric tests and accuracy measures were calculated. Results Out of 60 patients included, 8 were N, 12 HF, 11 I and 29 PE. Gas6 median value in the N group (20.4 ng/mL, interquartile range 17.6–21.6) matched that of healthy volunteers, 19.1 (17.2–21.4). Median Gas6 values in HF, 26.4 (21.6–33.3) and I groups, 34.1 (30.0–38.7), were significantly higher than those in PE 18.2 (16.3–23.3) or N (Kruskal–Wallis test p ≤ 0.05) groups. Gas6 test improved PE diagnosis with an area under the curve of 0.80 and 0.91 (in all and LICP patients). A 24 ng/mL threshold excluded PE in 33% of LICP patients without loosing any diagnosis. Conclusions The data link Gas6 protein to infection/inflammation, but not to PE, in humans. Gas6 assay was useful in PE diagnosis, improving D-dimer accuracy particularly in LICP patients, and limiting false positives.
Traditional indexes of LV dyssynchrony (DYS) in pts to be resynchronized are sensitive to noise, while the concordance between LV lead position and site of latest mechanical activation is suggested ...to be, in these patients, clinically relevant. Both aspects, asynchrony and lead position have been addressed separately but unclear is their potential synergistic role in the clinical evolution of CRT patients. We assessed clinical and echocardiographic outcome, as well as mid-term prognosis, in a population of CHF patients submitted to CRT, stratified according to a novel asynchrony quantitation (temporal uniformity of strain: TUS) method and concordance or not between presumed LV lead position and site of latest mechanical activation. TUS was computed in 85 pts (QRS > 120 ms, EF < 0.35) in whom we measured circumferential and longitudinal strains using speckle-tracking 2D-echocardiography before and 3–6 months after CRT, together with triplane apical LV volumes. Optimal LV lead position in short axis view was defined as concordance of the segment with latest systolic circumferential strain prior-CRT and segment with assumed LV lead position. Assumed LV lead position was defined from a chest X-ray obtained 1 day after implantation and scored as anterior, lateral, posterior or inferior using 2 orthogonal views (antero-posterior and lateral). Following CRT, LV volume decreased (diastolic −8 ± 20%) and EF improved (+6 ± 9%,
P
< 0.001 for both). Two-way ANOVA revealed TUS improvement post-CRT (+22 ± 68%,
P
= 0.025), with a clear evidence for more marked asynchrony detectable at circumferential (from 0.53 ± 0.20 to 0.55 ± 0.19) as compared with longitudinal level (from 0.56 ± 0.14 to 0.62 ± 0.14) (
P
= 0.017). Multivariate analysis revealed that greater baseline asynchrony, as assessed circumferentially (
P
= 0.079), together with concordance between LV lead position and site of activation (
P
= 0.012), besides younger age (
P
= 0.051), longer QRS duration (
P
= 0.021) and higher baseline EF (
P
= 0.04),), but not longitudinal TUS (
P
= 0.231) did predict death from any cause or new episodes of pulmonary or systemic congestion requiring i.v. diuretics during a 529 ± 357 days clinical follow-up. We conclude that DYS indexed by circumferential TUS yields CRT benefits, supporting the idea of targeting TUS-measured DYS as the informative asynchrony quantitative measurement in CRT pts. Significant predictability in medium-term clinical follow-up of patients to be resynchronized is also associated with concordance between site of latest mechanical activation and presumed LV lead position in the present study.
To analyze the inter-observer variability and the potential impact of 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) imaging for target volume delineation in ...preoperative radiotherapy of rectal cancer. Gross tumor volume (GTV) and clinical target volume (CTV) in 2 cases of rectal cancer were contoured by 10 radiation oncologists, 5 on CT and 5 on PET/CT images. Resulting volumes were analyzed by coefficient of variation (CV) and concordance index (CI). Mean GTV was 120 cc±20.4 cc in case A and 119 cc ± 35.7 cc in case B. Mean CTV was 723 cc ± 147.5 cc in case A and 739 cc ± 195.6 cc in case B. CV was lower and CI was similar or higher across the observers contouring GTV on PET/CT. CTV variability was less influenced by the use of PET/CT. PET/CT may allow reducing inter-observer variability in GTV delineation.
Interventional procedures on peripheral vessels are the field of a novel specialty dedicated to the diagnosis and minimally invasive endovascular treatment of diseases involving the cerebral, ...thoracic and abdominal arteries (including renal and visceral arteries), as well as the peripheral arteries (femoro-popliteal arteries and the arteries below the knee). At present, physicians with three different types of medical training, each involving particular strengths and characteristics, specialize in endovascular treatment of patients with peripheral arterial disease: vascular surgeons, interventional radiologists and interventional cardiologists. Treatment of high-risk patients in terms of anatomical and clinical (serious comorbidities) complexity raised the need for the interventional cardiologist to face issues related to technical aspects of the procedure, multilevel pathology management and adequate indication. To achieve this goal, interventional cardiologists require particular facilities and clinical skills. The objectives of this position paper from the Italian Society of Interventional Cardiology (SICI-GISE) are (i) to define the theoretical background and practical training required to ensure that interventional cardiologists maintain high-quality standards also in the field of treatment of peripheral arterial disease, by establishing shared rules and drafting papers; (ii) to standardize the procedures of interventional cardiology operational units that treat patients with peripheral arterial disease in Italy on the basis of scientific evidence, and (iii) to establish common requirements in terms of facilities and regulations.
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