FAPI PET uptake patterns after invasive medical interventions: a single center retrospective analysis.

PURPOSE: Fibroblast activation protein (FAP)-inhibitor (FAPI)-PET tracers allow imaging of the FAP-expressing cancer associated fibroblasts (CAF) and also the normal activated fibroblasts (NAF) involved in inflammation/fibrosis that may be present after invasive medical interventions. We evaluated [68Ga]Ga-FAPI-46 uptake patterns post-medical/invasive non-systemic interventions. METHODS: This single-center retrospective analysis was conducted in 79 consecutive patients who underwent [68Ga]Ga-FAPI-46 PET/CT. Investigators reviewed prior patient medical/invasive interventions (surgery, endoscopy, biopsy, radiotherapy, foreign body placement (FBP) defined as implanted medical/surgical material present at time of scan) and characterized the anatomically corresponding FAPI uptake intensity both visually (positive if above surrounding background) and quantitatively (SUVmax). Interventions with missing data/images or confounders of [68Ga]Ga-FAPI-46 uptake (partial volume effect, other cause of increased uptake) were excluded. Available correlative FDG, DOTATATE and PSMA PET/CTs were analyzed when available. RESULTS: 163 medical/invasive interventions (mostly surgeries (49%), endoscopies (18%) and non-surgical biopsies (10%)) in 60 subjects were included for analysis. 43/163 (26%) involved FBP. FAPI uptake occurred in 24/163 (15%) of interventions (average SUVmax 3.2 (mild), range 1.5-5.1). The median time-interval post-intervention to FAPI-PET was 47.5 months and was shorter when FAPI uptake was present (median 9.5 months) than when absent (median 60.1 months; p = 0.001). Cut-off time beyond which no FAPI uptake would be present post-intervention without FBP was 8.2 months, with a sensitivity, specificity, positive predictive value and negative predictive value of 82, 90, 99 and 31% respectively. No optimal cutoff point could be determined when considering interventions with FBP. No significant difference was detected between frequency of [68Ga]Ga-FAPI-46 and [18F]FDG uptake in intervention sites. Compared to [68Ga]Ga-PSMA-11, [68Ga]Ga-FAPI-46 revealed more frequent and intense post-interventional tracer uptake. CONCLUSION: [68Ga]Ga-FAPI-46 uptake from medical/invasive interventions without FBP appears to be time dependent, nearly always absent beyond 8 months post-intervention, but frequently present for years with FBP.

Characterizing Normal Variant [68Ga]Ga-FAPI-46 Uptake in the Epididymis.

The biodistribution of fibroblast activation protein inhibitor (FAPI) PET tracers includes the kidneys, bladder, uterus, breast, muscles, and bone marrow. We describe its occasional uptake patterns in the epididymis. Methods: Epididymal [68Ga]Ga-FAPI-46 uptake was retrospectively analyzed in 55 PET/CT studies of 55 men. Uptake intensity (SUV), pattern (diffuse, focal, or multifocal), laterality, and location (epididymal head with or without body/tail) were analyzed. Electronic medical records were reviewed to determine the presence of epididymis-related disease. Results: Epididymal [68Ga]Ga-FAPI-46 uptake was observed in 8 of 55 (15%) subjects, with bilateral epididymal head uptake in all cases and epididymal body/tail uptake in 6 of 8 (75%) cases, 5 of 6 (83%) bilaterally and 1 of 6 (17%) unilaterally. The average SUVmax was greater in the epididymal heads than in the epididymal bodies/tails, with an SUVmax of 4.1 versus 3.0 (P < 0.001). No subject had epididymal disease related to the uptake. Conclusion: [68Ga]Ga-FAPI-46 uptake in the epididymis occurs occasionally and does not appear related to epididymal disease.

Over the Counter Supplements for Memory: A Review of Available Evidence.

In 2021, the Global Brain Health Supplement Industry Market size was valued at US$7.6 billion. It is predicted to increase to US$15.59 billion by 2030. Memory and its enhancement are a segment of the market that comprised the highest global revenue share in 2021. In the USA alone, dietary supplement sales reached US$18 billion in 2018. The US Food and Drug Administration (FDA) does not have the authority to approve dietary supplements' safety, effectiveness, or labeling before products go on the market. The FDA often does not even review supplements before they go to market. Supplement manufacturers are thus responsible for ensuring their products are safe and that their claims are truthful. An extensive review of current supplements on the market was performed by surveying memory products for sale at local and national pharmacies and grocery stores. A list of 103 supplements was compiled and the ingredients in these memory supplements were reviewed. The 18 most common ingredients in these supplements were identified. Each of the supplements included at least one of the 18 most common ingredients. Scientific data relative to these ingredients and their effect on memory was searched using PubMed and Cochrane library databases. Currently, there is no compelling evidence for use of apoaequorin, coenzyme Q10, coffee extracts, L-theanine, omega-3 fatty acids, vitamin B6, vitamin B9, or vitamin B12 supplementation for memory. On the other hand, there is some current evidence for memory benefit from supplementation with ashwagandha, choline, curcumin, ginger, Lion's Mane, polyphenols, phosphatidylserine, and turmeric. There are current studies with mixed results regarding the benefit of carnitine, gingko biloba, Huperzine A, vitamin D, and vitamin E supplementation for memory. Dietary supplements geared toward improving cognition are a billion-dollar industry that continues to grow despite lacking a solid scientific foundation for their marketing claims. More rigorous studies are needed relative to the long-term use of these supplements in homogenous populations with standardized measurements of cognition. Health care providers need to be aware of any and all supplements their older adult patients may be consuming and be educated about their side effects and interactions with prescription medications. Lastly, the FDA needs to take an active position relative to monitoring marketed supplements regarding safety, purity and claims of efficacy.

The aquaporin-4 water channel and updates on its potential as a drug target for Alzheimer's disease.

INTRODUCTION: Although there are several FDA-approved treatments for Alzheimer's disease (AD), only recently have disease-modifying therapies received approval for use in patients. In this narrative review, we examine the history of aquaporin-4 (AQP4) as a therapeutic target for NMOSD (neuromyelitis optica spectrum disorder) and as a potential therapeutic target for AD. AREAS COVERED: We review the basic science and discovery of AQP4, a transmembrane water-channel essential to regulating water balance in the central nervous system (CNS). We also review the pathogenesis of NMOSD, an autoimmune disease characterized by the destruction of cells that express AQP4. Then, we review how AQP4 is likely involved in the pathogenesis of Alzheimer's disease (AD). Finally, we discuss future challenges with drug design that would modulate AQP4 to potentially slow AD development. The literature search for this article consisted of searching Google Scholar and PubMed for permutations of the keywords 'Alzheimer's disease,' 'aquaporin-4,' 'neuromyelitis optica,' and their abbreviations. EXPERT OPINION: We place research into AQP4 into context with other recent developments in AD research. A major difficulty with drug development for Alzheimer's is the lack of strategies to cleanly target the early pathogenesis of the disease. Targeting AQP4 may provide such a strategy.

Comparing digital to analog prostate-specific membrane antigen-targeted piflufolastat 18 F PET/CT in prostate cancer patients in early biochemical failure.

PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography/computer tomography (PET/CT) in prostate cancer patients with biochemical failure(BCF) showslimited sensitivity when the prostate-specific antigen(PSA) <0.5 ng/mL. The development of digital PET/CT has greatly improved smaller lesion detection. This study's goal was to compare the performance and clinical value of PSMA-targeted piflufolastat PET/CT for prostate cancer BCF with digital versus analog PET/CT. METHODS: In this retrospective study, all piflufolastat PET/CT scans in subjects with PSA ≤ 3.0 ng/mL who were referred for prostate cancer BCF were included. The performance characteristics of 171 analog PET/CT studies in 155 subjects from May 2017 to January 2020 and 106 digital PET/CT studies in 103 subjects from February 2020 to December 2020 were compared. Lesions were considered malignant if they did not match the known physiological distribution of piflufolastat and did not represent uptake in benign lesions. PSMA PET/CT studies were considered positive if at least one malignant lesion was detected and negative if none were detected. RESULTS: Digital piflufolastat PET/CT outperformed analog piflufolastat PET/CT in subjects with PSA < 0.5 ng/mL with a positivity rate of 69% versus 37%, respectively. In patients with PSA ≥ 0.5 ng/mL, both technologies performed similarly. There was no statistically significant difference between the number or size of piflufolastat-avid lesions detected per PET/CT study. CONCLUSION: In prostate cancer patients with BCF and PSA < 0.5 ng/mL, digital piflufolastat PET/CT has a higher detection rate of malignant lesions than analog piflufolastat PET/CT.

Cannabis Use and Misuse in Older Adults.

Cannabis is the most frequently used illegal psychoactive substance by older adults. With population aging, legalization and medicalization of cannabis, and changes in perceptions of older adults toward its use, recreational and medical cannabis use/misuse is on the rise in seniors. Although there are solid data related to the adverse events of cannabis in older adults, efficacy data are lacking. Older adults are at increased risk of developing cannabis use disorder alongside other medical and psychiatric comorbidities. We review the benefits and risks associated with cannabis use, and screening and management strategies for cannabis use disorder in older adults.

Physiologic prostate-specific membrane antigen-targeted 18F-DCFPyL uptake in the epididymis head newly appreciated on digital PET/CT.

PURPOSE: The published physiological distribution of prostate specific membrane antigen (PSMA) PET ligands includes normal uptake in the lacrimal glands, salivary glands, bowel, liver, spleen, kidneys and parasympathetic ganglia but does not include the epididymis. METHODS: Retrospective review of 134 PSMA-targeted 2-(3-(1-carboxy-5-[(6-[18F]fluoropyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid (18F-DCFPyL) PET/CT scans performed on a latest generation digital scanner for radiotracer uptake in the epididymal head region was correlated with multiple clinical and laboratory factors. RESULTS: Physiologic PSMA radiotracer uptake in the epididymal head region was present in 57% of all subjects, including 29% in those with a total serum testosterone ≤ 5 nmol/L and 65% of patients with serum testosterone > 5 nmol/L, odds ratio of 0.21 (P < 0.01). CONCLUSION: Epididymal head uptake is physiologic and very common on digital PSMA PET/CT and is more frequent in patients with higher serum testosterone levels. The enhanced small structure detection of digital PET/CT is the most likely explanation for the novel visualization of this normal variant.

Weight loss as primary indication for FDG-PET/CT.

PURPOSE: Some consider fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) clinically useful in patients presenting with nonspecific symptoms of malignancy, weight loss most commonly encountered. However, the appropriateness of such FDG-PET/CT studies remains to be clarified. This study evaluated the clinical value of FDG-PET/CT in patients referred primarily for weight loss. METHODS: From 2010 to 2017 in one academic center, 252 subjects underwent 254 FDG-PET/CT studies for weight loss as primary indication and retrospectively studied. Eighteen subjects were excluded due to ongoing active malignancy, weight loss not ultimately being the main indication for the FDG-PET/CT, technically inadequate FDG-PET/CT and insufficient follow-up. The FDG-PET/CT scans were considered clinically beneficial when true positive for the cause of weight loss that other investigations missed or would have missed, clinically neutral when true negative and clinically detrimental when false positive leading to additional investigations or false negative. RESULTS: Ultimately 234 unique subjects (236 FDG-PET/CT studies) were included. The average subject weight loss prior to the PET was 12 kg and average follow-up time post FDG-PET/CT scan was 3.4 years. The FDG-PET/CT scans were true positive in 24 studies (10%) with 8 studies (3%) clinically beneficial; false positive in 38 studies (16%) of which 26 led to 35 additional procedures and false negative in 13 studies (6%). In total, 39 (17%) FDG-PET/CT studies were clinically detrimental. The other 149 (63%) studies were true negative, clinically neutral. CONCLUSION: FDG-PET/CT appears to have limited value in assessing subjects with weight loss as the leading clinical indication, proving to be five times more often detrimental than beneficial.

18F-FDG PET/CT versus conventional investigations for cancer screening in autoimmune inflammatory myopathy in the era of novel myopathy classifications.

BACKGROUND: To compare the performance of fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) and conventional tests for cancer screening in autoimmune inflammatory myopathy (AIM) patients. PATIENTS AND METHODS: We carried out a retrospective cohort study of AIM patients from one academic center in Montreal, Canada, classified using myositis-specific antibodies, who underwent F-FDG PET/CT between April 2005 and February 2018 and were followed up on average 3.5±2.4 years. Patients were excluded if follow-up was insufficient, AIM diagnosis was indeterminate, and/or malignancy was diagnosed before an F-FDG PET/CT scan. Demographic/clinical data, F-FDG PET/CT results, and available conventional screening tests results were retrieved from electronic and paper medical records. RESULTS: 100 F-FDG PET/CT studies in 63 unique patients [31/63 dermatomyositis (DM), 25/63 overlap myositis, 1/63 inclusion body myositis, 1/63 polymyositis, 1/63 orbital myositis and 4/63 unspecified myositis] were evaluated. Three patients, all classified as DM, were diagnosed with cancer during follow-up with conventional cancer screening tests: breast cancer detected by mammography; squamous cell carcinoma of the skin detected by physical examination; and multiple myeloma detected by blood work. F-FDG PET/CT did not detect any malignancy and led to more additional biopsies than conventional screening (8 vs. 5). CONCLUSION: F-FDG PET/CT does not appear to be useful in cancer screening for AIM patients compared with conventional screening and carries potential harms associated with follow-up investigations. The risk of cancer in AIM differs by myositis-specific antibodies-defined subsets and cancer screening is likely to be indicated only in high-risk patients, particularly DM. These results, replicated in larger, multicentered studies, may carry significant consequences for optimal management of AIM and health resource utilization.

Acinetobacter spp in a Third World Country with Socio-economic and Immigrants Challenges.

INTRODUCTION: In the last decade, Acinetobacter species have taken a major public health concern. This is mainly due the increased resistance to a wide range of antibiotics causing treatment challenges. In view of the constant population mobilization and the economic crisis that Lebanon is currently facing, it becomes a necessity to re-evaluate the real threat of Acinetobacter spp and its implication in the one health. METHODOLOGY: This review was conducted through the analysis of 45 research papers and reports pertaining to Acinetobacter spp performed in Lebanon. More than 82% of the papers consulted were published in international journals and more than 70 percent of them had received impact factor. RESULTS: An in depth description of the involvement of this organism in human infection and its role as potential pathogen or simple colonizer was performed. In addition, the different aspects of resistance, mostly to carbapenems and colistin was studied and summarized. While in animals and environment, susceptible strains were mostly isolated, OXA-23/OXA-24 were predominant in humans. Recently, NDM-1 producing Acinetobacter spp was detected in a Syrian refugee which then was reported in Lebanese patients. The bacterial identification procedures are non-systematic and not always reliable in the Lebanese studies presenting sometimes discrepancies an inconsistency. CONCLUSION: Acinetobacter is commonly isolated Lebanon. In view of the spread of resistance among these isolated and their dissemination, Infection control measures attempting to control the spread of this genus in and outside hospitals are lacking and thus require more attention and stewardship activities.

A case of severe Pembrolizumab-induced neutropenia.

Immune checkpoint inhibitors have revolutionized cancer therapy. Given their mechanism of action, immune-related adverse events have been associated with their use. We present the first documented case of pembrolizumab-induced grade IV neutropenia. A 73-year-old women known for myositis, Crohn's disease, and hypothyroidism and diagnosed with PD-L1 positive stage IV pulmonary adenocarcinoma is treated with Pembrolizumab. She develops grade IV neutropenia 2 weeks after her second infusion. She is therefore hospitalized and treated initially with corticosteroids, granulocyte colony-stimulating factor, and intravenous immunoglobulins. Given the persistent neutropenia, cyclosporine was added, but quickly stopped owing to fever. The patient recovered her neutrophils 6.5 weeks after her initial Pembrolizumab infusion and 12 days after admission. She has been subsequently successfully tapered off steroids with no recurrence after 3 months of follow-up. This is the first case of grade IV neutropenia secondary to Pembrolizumab. This case is of particular interest given the patient's pre-existing autoimmune history. Treatment of severe neutropenia due to other PD1 inhibitors has generally consisted of steroids, granulocyte colony-stimulating factor, intravenous immunoglobulins, mycophenolate mofetil, cyclosporine A, and anti-thymocyte globulins - though the benefits of immunosuppression are not clear and may be harmful given the infectious risks. Large studies are required to clarify the spectrum and optimal management of immune-related adverse events and overall risk/benefits of immune checkpoint inhibitors in patients with pre-existing autoimmunity.

ESBL-producing Escherichia coli and Klebsiella pneumoniae in two major Lebanese hospitals: molecular epidemiology and correlation with consumption.

INTRODUCTION: Extended-spectrum - beta lactamases (ESBLs) are increasingly detected globally among Escherichia coli and Klebsiella pneumoniae. The correlation between antibiotics use and resistance, though not fully described, has been addressed and shown in several studies. In this study, the profiles of ESBLs in E. coli and K. pneumoniae isolated from two Lebanese hospitals and their relationship to antibiotic consumption were determined. METHODOLOGY: A total of 205 E. coli and 67 K. pneumoniae isolates resistant to third- or fourth-generation cephalosporins were collected between January 2011 and January 2012. Antibiotic susceptibility and consumption data were also collected from 2010-2012. Double-disk synergy and Etest ESBL assays were performed, followed by PCR for ESBL genes. Pulsed-field gel electrophoresis (PFGE) was performed for representative isolates. Statistical analysis for consumption and susceptibility data over 3 years was performed. RESULTS: As expected, CTX-M-15 was predominant. In both hospitals, strains of E. coli and K. pneumoniae harbored at least one ESBL, and in some cases (23%) harboured four different ESBLs. A significant correlation was detected between total use of antimicrobial agents and resistance to various antibiotics. This was obvious for the use of penicillins and resistance to aztreonam, ceftazidime and ciprofloxacin, and use of third- and fourth-generation cephalosporins and resistance to ceftazidime, cefuroxime, cefoxitin and ciprofloxacin in both bacteria. CONCLUSIONS: This study shows the predominance of CTX-M-15 among cephalosporin-resistant E. coli and K. pneumoniae in Lebanese hospitals and highlights the direct relationship between the use of antibiotics and the emergence of resistance in bacteria.