PET/CT/MRI in Clinical Trials of Alzheimer's Disease.

With the advent of PET imaging in 1976, 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-PET became the preferred method for in vivo investigation of cerebral processes, including regional hypometabolism in Alzheimer's disease. With the emergence of amyloid-PET tracers, [11C]Pittsburgh Compound-B in 2004 and later [18F]florbetapir, [18F]florbetaben, and [18F]flumetamol, amyloid-PET has replaced FDG-PET in Alzheimer's disease anti-amyloid clinical trial treatments to ensure "amyloid positivity" as an entry criterion, and to measure treatment-related decline in cerebral amyloid deposits. MRI has been used to rule out other brain diseases and screen for 'amyloid-related imaging abnormalities' (ARIAs) of two kinds, ARIA-E and ARIA-H, characterized by edema and micro-hemorrhage, respectively, and, to a lesser extent, to measure changes in cerebral volumes.

Biomechanical changes in keratoconus after customized stromal augmentation.

Purpose: To verify corneal biomechanical changes, poststromal augmentation using myopic small-incision lenticule extraction's (SMILEs) lenticules in advanced keratoconus (KCN) through Corvis ST (Oculus, Wetzlar, Germany).

Materials And Methods: A clinical trial enrolled 22 advanced KCN patients. We implanted lenticules exceeding 100 μ according to a nomogram and evaluated biomechanical factors through Corvis ST at 3-, 6-, and 24-month postimplantation.

Main issues in deep anterior lamellar keratoplasty: A systematic narrative review.

Deep anterior lamellar keratoplasty (DALK) has emerged as a transformative approach in managing corneal pathologies, notably keratoconus (KC), providing a viable alternative to penetrating keratoplasty (PK). This systematic review explores the intricacies of DALK, comparing its preoperative, intraoperative, and postoperative considerations with PK. Extensive literature searches revealed a wealth of data regarding DALK's advantages and challenges, with an emphasis on graft survival, visual outcomes, and complications.

Main issues in penetrating keratoplasty.

This review explores contemporary challenges in penetrating keratoplasty (PK), focusing on technical intricacies, technological advancements, and strategies for preventing graft rejection. A systematic literature search from January 2018 to July 2023 was conducted across PubMed, Cochrane, Web of Science, Scopus, and EMBASE. The inclusion criteria comprised studies on PK and its comparison with other corneal pathologies, with emphasis on keratoconus (KC).

Revision of Alzheimer's diagnostic criteria or relocation of the Potemkin village.

The recently announced revision of the Alzheimer's disease (AD) diagnostic ATN classification adds to an already existing disregard for clinical assessment the rejection of image-based in vivo assessment of the brain's condition. The revision suggests that the diagnosis of AD should be based solely on the presence of cerebral amyloid-beta and tau, indicated by the "A" and "T". The "N", which stands for neurodegeneration - detected by imaging - should no longer be given importance, except that A+ ± T + = AD with amyloid PET being the main method for demonstrating A+ .

A community outbreak of Legionnaires' disease caused by outdoor hot tubs for private use in a hotel.

During the period October-November 2017, an outbreak of Legionnaires' disease involving 27 cases occurred in the tourist area of Palmanova (Mallorca, Spain). The majority of cases were reported by the European Centre of Disease Prevention and Control (ECDC) as travel associated cases of Legionnaires' disease (TALD). Most cases belonged to different hotel cluster alerts.

Amyloid PET: A Questionable Single Primary Surrogate Efficacy Measure on Alzheimer Immunotherapy Trials.

Using amyloid PET imaging as a single primary surrogate efficacy measure in Alzheimer's disease immunotherapy trials, as happened when the FDA granted accelerated approval of aducanumab, is unjustified. In vivo evidence indicates that PET quantification of amyloid deposition is distorted and misrepresents effects of anti-amyloid treatments due to lack of specificity of the PET imaging probe, effects of amyloid-related imaging abnormalities, spill-over from high white matter signals, and questionable quantification models. Before granting approval to other immunotherapy candidates, the FDA should require rigorous evidence of all imaging claims and irrefutable documentation that proposed treatments are clinically effective and harmless to patients.

Light scattering in intraocular lenses explanted 15 to 40 years after surgery.

The optical quality of intraocular lenses (IOLs) of different materials that have been implanted from 16 to 44 years in human eyes was studied. The IOLs were explanted due to other causes than loss of transparency. The scattered light from the IOLs was assessed in two angular regimes by using dark field images (for wide angles) and the optical integration method (for narrower angles).

Amyloid Hypothesis: The Emperor's New Clothes?

The lengthy debate on the validity of the amyloid hypothesis and the usefulness of amyloid imaging and anti-amyloid therapeutic interventions in dementia continues unabated, even though none of them have been able to convince the medical world of their correctness and clinical value. There are huge financial interests associated with promoting both, but in spite of the large sums of money in their support, no effective anti-amyloid treatments or diagnostic use of amyloid imaging have emerged. There are solid scientific reasons that explain these negative results, and it is time to move forward to other promising options for the benefit of the patients.

[F]FDDNP PET binding predicts change in executive function in a pilot clinical trial of geriatric depression.

Objectives: Geriatric depression often presents with memory and cognitive complaints that are associated with increased risk for Alzheimer's disease (AD). In a parent clinical trial of escitalopram combined with memantine or placebo for geriatric depression and subjective memory complaints, we found that memantine improved executive function and delayed recall performance at 12 months (NCT01902004). In this report, we used positron emission tomography (PET) to assess the relationship between in-vivo amyloid and tau brain biomarkers and clinical and cognitive treatment response.

Probing Estrogen Sulfotransferase-Mediated Inflammation with [11C]-PiB in the Living Human Brain.

Background: 2-(4'- [11C]Methylaminophenyl)-6-hydroxybenzothiazole ([11C]-PiB), purportedly a specific imaging agent for cerebral amyloid-β plaques, is a specific, high affinity substrate for estrogen sulfotransferase (SULT1E1), an enzyme that regulates estrogen homeostasis.

Objective: In this work, we use positron emission tomography (PET) imaging with [11C]-PiB to assess the functional activity of SULT1E1 in the brain of moyamoya disease patients.

Methods: Ten moyamoya subjects and five control patients were evaluated with [11C]-PiB PET and structural MRI scans.

Does 2-FDG PET Accurately Reflect Quantitative In Vivo Glucose Utilization?

2-Deoxy-2-F-fluoro-d-glucose (2-FDG) with PET is undeniably useful in the clinic, being able, among other uses, to monitor change over time using the 2-FDG SUV metric. This report suggests some potentially serious caveats for this and related roles for 2-FDG PET. Most critical is the assumption that there is an exact proportionality between glucose metabolism and 2-FDG metabolism, called the lumped constant, or LC.

Longer TOMM40 poly-T variants associated with higher FDDNP-PET medial temporal tau and amyloid binding.

Background: The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with the apolipoprotein E (APOE) gene, has been implicated in Alzheimer's disease (AD). TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. While early reports indicated that the longer length poly-T allele of TOMM40 increases risk for AD, these findings have not been consistently replicated in further studies.

Sodium-glucose transporter 2 is a diagnostic and therapeutic target for early-stage lung adenocarcinoma.

The diagnostic definition of indeterminate lung nodules as malignant or benign poses a major challenge for clinicians. We discovered a potential marker, the sodium-dependent glucose transporter 2 (SGLT2), whose activity identified metabolically active lung premalignancy and early-stage lung adenocarcinoma (LADC). We found that SGLT2 is expressed early in lung tumorigenesis and is found specifically in premalignant lesions and well-differentiated adenocarcinomas.

The Value of In Vitro Binding as Predictor of In Vivo Results: A Case for [F]FDDNP PET.

Purpose: Caution is warranted when in vitro results of biomarkers labeled with tritium were perfunctorily used to criticize in vivo data and conclusions derived with the same tracers labeled with positron emitters and positron emission tomography (PET). This concept is illustrated herein with the PET utilization of [F]FDDNP, a biomarker used for in vivo visualization of β-amyloid and tau protein neuroaggregates in humans, later contradicted by in vitro data reported with [H]FDDNP. In this investigation, we analyze the multiple factors involved in the experimental design of the [H]FDDNP in vitro study that led to the erroneous interpretation of results.