The safety of magnetic resonance imaging contrast agents.

Gadolinium-based contrast agents are increasingly used in clinical practice. While these pharmaceuticals are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. We hypothesize that non-ligand-bound (soluble) gadolinium will be exceedingly low in patients. Soluble, ionic gadolinium is not likely to be the initial step in mediating any disease. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. We suspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models.

Implicit Theories of Happiness: When Happiness Is Viewed as Changeable, Happy People Are Perceived Much More Positively Than Unhappy People.

Happy people are often perceived positively, perhaps more than they actually are, whereas unhappy people are often perceived negatively, perhaps more than they actually are. What would make this bias stronger or weaker? The present research addresses this question by exploring the roles of implicit theories of happiness in the trait perceptions toward happy and unhappy people. Specifically, four studies (N = 998) tested hypotheses that an incremental theory of happiness would enhance and an entity theory of happiness would attenuate the trait perceptions favoring happy over unhappy people. Results found converging evidence that believing happiness as changeable (incremental theory) enhances the positive perceptions toward happy people, while providing less consistent evidence that believing happiness as fixed (entity theory) mitigates the negative perceptions toward unhappy people. The current research contributes to the literature on essentialism and advances the understanding of the roles of implicit theories of happiness in person perception.

Treatment of childhood disruptive behavior disorders and callous-unemotional traits: a systematic review and two multilevel meta-analyses.

BACKGROUND: Children with callous-unemotional (CU) traits are at high lifetime risk of antisocial behavior. It is unknown if treatments for disruptive behavior disorders are as effective for children with CU traits (DBD+CU) as those without (DBD-only), nor if treatments directly reduce CU traits. Separate multilevel meta-analyses were conducted to compare treatment effects on DBD symptoms for DBD+CU versus DBD-only children and evaluate direct treatment-related reductions in CU traits, as well as to examine moderating factors for both questions. METHODS: We systematically searched PsycINFO, PubMed, Cochran Library (Trials), EMBASE, MEDLINE, APA PsycNet, Scopus, and Web of Science. Eligible studies were randomized controlled trials, controlled trials, and uncontrolled studies evaluating child-focused, parenting-focused, pharmacological, family-focused, or multimodal treatments. RESULTS: Sixty studies with 9,405 participants were included (Mage  = 10.04, SDage  = 3.89 years, 25.09% female, 44.10% racial/ethnic minority). First, treatment was associated with similar reductions in DBD symptoms for DBD+CU (SMD = 1.08, 95% CI = 0.45, 1.72) and DBD-only (SMD = 1.01, 95% CI = 0.38, 1.64). However, DBD+CU started (SMD = 1.18, 95% CI = 0.57, 1.80) and ended (SMD = 0.73, p < .001; 95% CI = 0.43, 1.04) treatment with more DBD symptoms. Second, although there was no overall direct effect of treatment on CU traits (SMD = .09, 95% CI = -0.02, 0.20), there were moderating factors. Significant treatment-related reductions in CU traits were found for studies testing parenting-focused components (SMD = 0.21, 95% CI = 0.06, 0.35), using parent-reported measures (SMD = 0.16, 95% CI = 0.04, 0.28), rated as higher quality (SMD = 0.26, 95% CI = 0.13, 0.39), conducted outside the United States (SMD = 0.19, 95% CI = 0.05, 0.32), and with less than half the sample from a racial/ethnic minority group (SMD = 0.15, 95% CI = 0.002, 0.30). CONCLUSIONS: DBD+CU children improve with treatment, but their greater DBD symptom severity requires specialized treatment modules that could be implemented alongside parenting programs. Conclusions are tempered by heterogeneity across studies and scant evidence from randomized controlled trials.

Central and Peripheral Nervous System Complications of Vasculitis Syndromes from Pathology to Bedside: Part 2-Peripheral Nervous System.

PURPOSE OF REVIEW: Peripheral nervous system vasculitides (PNSV) are a heterogeneous group of disorders with a clinical subset that may differ in prognosis and therapy. We provide a comprehensive update on the clinical assessment, diagnosis, complications, treatment, and follow-up of PNSV. RECENT FINDINGS: Progress in neuroimaging, molecular testing, and peripheral nerve biopsy has improved clinical assessment and decision-making of PNSV, also providing novel insights on how to prevent misdiagnosis and increase diagnostic certainty. Advances in imaging techniques, allowing to clearly display the vessel walls, have also enhanced the possibility to differentiate inflammatory from non-inflammatory vascular lesions, while recent histopathology data have identified the main morphological criteria for more accurate diagnosis and differential diagnoses. Overall, the identification of peculiar morphological findings tends to improve diagnostic accuracy by defining a clearer boundary between systemic and non-systemic neuropathies. Therefore, the definition of epineurium vessel wall damage, type of vascular lesion, characterization of lymphocyte populations, antibodies, and inflammatory factors, as well as the identification of direct nerve damage or degeneration, are the common goals for pathologists and clinicians, who will both benefit for data integration and findings translation. Nevertheless, to date, treatment is still largely empiric and, in some cases, unsatisfactory, thus often precluding precise prognostic prediction. In this context, new diagnostic techniques and multidisciplinary management will be essential in the proper diagnosis and prompt management of PNSV, as highlighted in the present review. Thirty to fifty percent of all patients with vasculitis have signs of polyneuropathy. Neuropathies associated with systemic vasculitis are best managed according to the guidelines of the underlying disease because appropriate workup and initiation of treatment can reduce morbidity. Steroids, or in severe or progressive cases, cyclophosphamide pulse therapy is the standard therapy in non-systemic vasculitic neuropathies. Some patients need long-term immunosuppression. The use of novel technologies for high-throughput genotyping will permit to determine the genetic influence of related phenotypes in patients with PNSV.

Self-Continuity.

Self-continuity is the subjective sense of connection between one's past and present selves (past-present self-continuity), between one's present and future selves (present-future self-continuity), or among one's past, present, and future selves (global self-continuity). We consider the motivational character of the three forms of self-continuity, their regulatory properties, and the internal or external factors that consolidate them. We also review their consequences for attitudes and judgments or decisions, motivation, intentions and behavior, and psychological and physical health. We further detail the psychological and behavioral benefits of self-discontinuity (i.e., a sense of disconnect among temporal selves). We next turn to the brain regions that are activated synchronously with self-continuity. We consider developmental perspectives on self-continuity, discuss collective self-continuity (along with its consequences and regulatory properties), and elaborate on cultural differences in self-continuity. This inaugural Annual Reviews chapter demonstrates the breadth, excitement, and sense of synergy among self-continuity researchers and points to promising research directions.

Potential Application of Intranasal Insulin Delivery for Treatment of Intracerebral Hemorrhage: A Review of The Literature.

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke associated with high morbidity and mortality that is considered a medical emergency, mainly managed with adequate blood pressure control and creating a favorable hemostatic condition. However, to date, none of the randomized clinical trials have led to an effective treatment for ICH. It is vital to better understand the mechanisms underlying brain injury to effectively decrease ICH-associated morbidity and mortality. It is well known that initial hematoma formation and its expansion have detrimental consequences. The literature has recently focused on other pathological processes, including oxidative stress, neuroinflammation, blood-brain barrier disruption, edema formation, and neurotoxicity, that constitute secondary brain injury. Since conventional management has failed to improve clinical outcomes significantly, various neuroprotective therapies are tested in preclinical and clinical settings. Unlike intravenous administration, intranasal insulin can reach a higher concentration in the cerebrospinal fluid without causing systemic side effects. Intranasal insulin delivery has been introduced as a novel neuroprotective agent for certain neurological diseases, including ischemic stroke, subarachnoid hemorrhage, and traumatic brain injury. Since there is an overlap of mechanisms causing neuroinflammation in these neurological diseases and ICH, we believe that preclinical studies testing the role of intranasal insulin therapy in ICH are warranted.

Central and Peripheral Nervous System Complications of Vasculitis Syndromes From Pathology to Bedside: Part 1-Central Nervous System.

PURPOSE OF REVIEW: The aim of this review is to provide a comprehensive update on the clinical assessment, diagnosis, complications, and treatment of primary central nervous system vasculitis (PCNSV). RECENT FINDINGS: The developments in neuroimaging, molecular testing, and cerebral biopsy have enhanced clinical assessment and decision making, providing novel insights to prevent misdiagnosis increasing diagnostic certainty. Advances in imaging techniques visualizing the wall of intracranial vessels have improved the possibility to distinguish inflammatory from non-inflammatory vascular lesions. Large recent studies have revealed a more varied histopathological pictures and disclosed an association with amyloid angiopathy. Unfortunately, therapy remains largely empiric. PCNSV is a heterogeneous group of disorders encompassing different clinical subsets that may differ in terms of prognosis and therapy. Recent evidence has described a more benign course, with good response to therapy. New diagnostic techniques will play soon a pivotal role in the appropriate diagnosis and prompt management of PCNSV.

How Does Nostalgia Conduce to Global Self-Continuity? The Roles of Identity Narrative, Associative Links, and Stability.

In five studies (N = 1,074), we examined the relation-both correlational and causal-between nostalgia, a sentimental longing for one's past, and global self-continuity (GSC), a sense of connection among past, present, and future selves. Furthermore, we addressed mechanisms underlying this relation. We asked, in particular, whether nostalgic individuals might achieve GSC by constructing a narrative to give meaning to life transitions (narrative), connecting to the past (associative links), or believing in a self that is resistant to change (stability). Nostalgia predicted (Studies 1-3) and caused (Studies 4 and 5) GSC. The relation between nostalgia and GSC was consistently mediated by narrative, sporadically mediated by associative links, and unmediated by stability. The robust indirect effect via narrative remained significant when controlling for rumination (Study 3). We discuss theoretical and practical implications.

The Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 infection.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health challenge. This review aims to summarize the incidence, risk factors, possible pathophysiology, and proposed management of neurological manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC) or neuro-PASC based on the published literature. RECENT FINDINGS: The National Institutes of Health has noted that PASC is a multi-organ disorder ranging from mild symptoms to an incapacitating state that can last for weeks or longer following recovery from initial infection with SARS-CoV-2. Various pathophysiological mechanisms have been proposed as the culprit for the development of PASC. These include, but are not limited to, direct or indirect invasion of the virus into the brain, immune dysregulation, hormonal disturbances, elevated cytokine levels due to immune reaction leading to chronic inflammation, direct tissue damage to other organs, and persistent low-grade infection. A multidisciplinary approach for the treatment of neuro-PASC will be required to diagnose and address these symptoms. Tailored rehabilitation and novel cognitive therapy protocols are as important as pharmacological treatments to treat neuro-PASC effectively. With recognizing the growing numbers of COVID-19 patients suffering from neuro-PASC, there is an urgent need to identify affected individuals early to provide the most appropriate and efficient treatments. Awareness among the general population and health care professionals about PASC is rising, and more efforts are needed to understand and treat this new emerging challenge. In this review, we summarize the relevant scientific literature about neuro-PASC.

Nostalgia strengthens global self-continuity through holistic thinking.

Nostalgia, a sentimental longing for one's meaningful past, promotes global self-continuity (GSC), a sense of connection among one's past, present, and future selves. We identified a cognitive mechanism for this effect: holistic thinking, and in particular interactional causality (presupposing multiple causes that interact to influence an object's behaviour). In three studies, using measurement-of-mediation and experimental-causal-chain designs, nostalgia was related to, and caused, higher GSC through interactional causality. In cross-sectional Study 1, trait nostalgia was associated with GSC via interactional causality. In Study 2, induced nostalgia led to higher interactional causality and ensuing GSC. In Study 3, manipulated interactional causal thinking increased GSC.

64Cu-SARTATE PET Imaging of Patients with Neuroendocrine Tumors Demonstrates High Tumor Uptake and Retention, Potentially Allowing Prospective Dosimetry for Peptide Receptor Radionuclide Therapy.

Imaging of somatostatin receptor expression is an established technique for staging of neuroendocrine neoplasia and determining the suitability of patients for peptide receptor radionuclide therapy. PET/CT using 68Ga-labeled somatostatin analogs is superior to earlier agents, but the rapid physical decay of the radionuclide poses logistic and regulatory challenges. 64Cu has attractive physical characteristics for imaging and provides a diagnostic partner for the therapeutic radionuclide 67Cu. Based on promising preclinical studies, we have performed a first-time-in-humans trial of 64Cu-MeCOSar-Tyr3-octreotate (64Cu-SARTATE) to assess its safety and ability to localize disease at early and late imaging time-points. Methods: In a prospective trial, 10 patients with known neuroendocrine neoplasia and positive for uptake on 68Ga-DOTA-octreotate (68Ga-DOTATATE) PET/CT underwent serial PET/CT imaging at 30 min, 1 h, 4 h, and 24 h after injection of 64Cu-SARTATE. Adverse reactions were recorded, and laboratory testing was performed during infusion and at 1 and 7 d after imaging. Images were analyzed for lesion and normal-organ uptake and clearance to assess lesion contrast and perform dosimetry estimates. Results:64Cu-SARTATE was well tolerated during infusion and throughout the study, with 3 patients experiencing mild infusion-related events. High lesion uptake and retention were observed at all imaging time-points. There was progressive hepatic clearance over time, providing the highest lesion-to-liver contrast at 24 h. Image quality remained high at this time. Comparison of 64Cu-SARTATE PET/CT obtained at 4 h to 68Ga-DOTATATE PET/CT obtained at 1 h indicated comparable or superior lesion detection in all patients, especially in the liver. As expected, the highest early physiologic organ uptake was in the kidneys, liver, and spleen. Conclusion:64Cu-SARTATE is safe and has excellent imaging characteristics. High late-retention in tumor and clearance from the liver suggest suitability for diagnostic studies and for prospective dosimetry for 67Cu-SARTATE peptide receptor radionuclide therapy, and the half-life of 64Cu would also facilitate good-manufacturing-practice production and distribution to sites without access to 68Ga.

Cold Kit for Prostate-Specific Membrane Antigen (PSMA) PET Imaging: Phase 1 Study of 68Ga-Tris(Hydroxypyridinone)-PSMA PET/CT in Patients with Prostate Cancer.

68Ga-labeled urea-based inhibitors of the prostate-specific membrane antigen (PSMA), such as 68Ga-labeled N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED)-PSMA-11, are promising small molecules for targeting prostate cancer. A new radiopharmaceutical, 68Ga-labeled tris(hydroxypyridinone) (THP)-PSMA, has a simplified design for single-step kit-based radiolabeling. It features the THP ligand, which forms complexes with 68Ga3+ rapidly at a low concentration, at room temperature, and over a wide pH range, enabling direct elution from a 68Ge/68Ga generator into a lyophilized radiopharmaceutical kit in 1 step without manipulation. The aim of this phase 1 study was to assess the safety and biodistribution of 68Ga-THP-PSMA. Methods: Cohort A comprised 8 patients who had proven prostate cancer and were scheduled to undergo prostatectomy; they had Gleason scores of 7-10 and a mean prostate-specific antigen level of 7.8 µg/L (range, 5.4-10.6 µg/L). They underwent PET/CT after the administration of 68Ga-THP-PSMA. All patients proceeded to prostatectomy (7 with pelvic nodal dissection). Dosimetry from multi-time-point PET imaging was performed with OLINDA/EXM. Cohort B comprised 6 patients who had positive 68Ga-HBED-PSMA-11 PET/CT scanning results and underwent comparative 68Ga-THP-PSMA scanning. All patients were monitored for adverse events. Results: No adverse events occurred. In cohort A, 6 of 8 patients had focal uptake in the prostate (at 2 h: average SUVmax, 5.1; range, 2.4-9.2) and correlative 3+ staining of prostatectomy specimens on PSMA immunohistochemistry. The 2 68Ga-THP-PSMA scans with negative results had only 1+/2+ staining. The mean effective dose was 2.07E-02 mSv/MBq. In cohort B, 68Ga-THP-PSMA had lower physiologic background uptake than 68Ga-HBED-PSMA-11 (in the parotid glands, the mean SUVmax for 68Ga-THP-PSMA was 3.6 [compared with 19.2 for 68Ga-HBED-PSMA-11]; the respective corresponding values in the liver were 2.7 and 6.3, and those in the spleen were 2.7 and 10.5; P < 0.001 for all). In 5 of 6 patients, there was concordance in the number of metastases identified with 68Ga-HBED-PSMA-11 and 68Ga-THP-PSMA. Thirteen of 15 nodal abnormalities were subcentimeter. In 22 malignant lesions, the tumor-to-liver contrast with 68Ga-THP-PSMA was similar to that with 68Ga-HBED-PSMA (4.7 and 5.4, respectively; P = 0.15), despite a higher SUVmax for 68Ga-HBED-PSMA than for 68Ga-THP-PSMA (30.3 and 10.7, respectively; P < 0.01). Conclusion:68Ga-THP-PSMA is safe and has a favorable biodistribution for clinical imaging. Observed focal uptake in the prostate was localized to PSMA-expressing malignant tissue on histopathology. Metastatic PSMA-avid foci were also visualized with 68Ga-THP-PSMA PET. Single-step production from a Good Manufacturing Practice cold kit may enable rapid adoption.

Companion Versus Comparison: Examining Seeking Social Companionship or Social Comparison as Characteristics That Differentiate Happy and Unhappy People.

Which friend do you want to spend time with-a happy friend who performs better than you or an unhappy friend who performs worse than you? The present research demonstrates that in such conflicting situations, when the desires for companionship and comparison are pitted against each other, one's level of happiness plays an important role in one's choice. Using hypothetical scenarios, we found that compared with unhappy people, happy people expected that spending time with a happy, superior friend would be more pleasant than spending time with an unhappy, inferior friend (Studies 1B through 2) and were more willing to socialize with a happy, superior friend than with an unhappy, inferior friend (Studies 1B through 2). Moreover, this pattern was not explained by self-esteem (Study 2) or the similarity-attraction hypothesis (Study 3). The present findings suggest that happy people place more value on companionship than on comparison.

High management impact of Ga-68 DOTATATE (GaTate) PET/CT for imaging neuroendocrine and other somatostatin expressing tumours.

INTRODUCTION: Ga-68 DOTATATE (Ga-octreotate, GaTate) positron emission tomography (PET)/CT has multiple advantages compared with conventional and In-111 octreotide imaging for neuroendocrine tumours and other somatostatin-receptor expressing tumours. This study assesses the management impact of incremental diagnostic information obtained from this technique compared with conventional staging. METHODS: Fifty-nine GaTate PET/CT studies were performed over an 18-month period (52 proven or suspected gastro-entero-pancreatic or bronchial neuroendocrine tumours and seven neural crest/mesenchymal tumours). A retrospective blinded review was performed on the number of abnormalities (1, 2-5 or >5) within defined regions with comparison to conventional imaging to assess incremental diagnostic information. Subsequent management impact (high, moderate or low) was determined by clinical review and follow up to assess pre-PET stage, treatment intent and post-PET management change. RESULTS: Eighty-eight percent of GaTate studies were abnormal. Compared with conventional and In-111 octreotide imaging, additional information was provided by GaTate PET/CT in 68 and 83% of patients, respectively. Management impact was high (inter-modality change) in 47%, moderate (intra-modality change) in 10% and low in 41% (not assessable in 2%). High management impact included directing patients to curative surgery by identifying a primary site and directing patients with multiple metastases to systemic therapy. CONCLUSION: GaTate PET/CT imaging provides additional diagnostic information in a high proportion of patients with consequent high management impact. GaTate PET/CT could replace (1)In-111 octreotide scintigraphy at centres where it is available given its superior accuracy, faster acquisition and lower radiation exposure. Rapid implementation could be achieved by allowing substitutional funding in the Medicare Benefit Schedule.

How do oncologists deal with incidental abnormalities on whole-body fluorine-18 fluorodeoxyglucose PET/CT?

BACKGROUND: Combined positron emission tomography (PET)/computed tomography (CT) using fluorine-18 fluorodeoxyglucose (FDG) is an exciting technique for cancer evaluation, but false-positive results are a recognized limitation. The aim of the study was to evaluate how oncologists deal with focal extrathyroidal FDG abnormalities considered by imaging specialists to be unrelated to the referral indication. METHODS: PET scan reports from a 12-month period from August 2002 to July 2003 in 1727 consecutive patients (mean age, 63 years) were reviewed. Incidental, nonphysiologic FDG abnormalities were classified based on the report conclusion. The frequency with which such abnormalities were investigated by oncologists and the final diagnosis were compared with the imaging diagnosis with a minimum potential follow-up of 2 years (mean, 27.5 months). RESULTS: Incidental FDG abnormalities were reported in 199 (12%) of 1727 patients, including 181 with adequate follow-up. Of 59 cases with a suspected second malignancy, 34 (58%) were actively investigated, with 14 confirmed, 7 unexpected metastatic sites, and 10 other active pathologies. Only 1 further cancer was subsequently detected in the 25 (42%) patients not actively investigated. Conversely, of 122 sites presumed to be benign, only 10 (8%) were actively investigated. Only 2 were proven to relate to malignancy. CONCLUSIONS: Although incidental abnormalities were common, most were benign and appropriately categorized by experienced readers. For actively investigated extrathyroidal abnormalities, a neoplastic basis was confirmed in over 60% of cases. Conversely, for cases deemed most likely benign by the PET/CT report or after review of readily available clinical information by the referring oncologist, the rate of malignancy was less than 2%.