Safety and feasibility of establishing an adjuvant hepatic artery infusion program.

BACKGROUND: Hepatic artery infusion (HAI) is less frequently used in the adjuvant setting for resectable colorectal liver metastasis (CRLM) due to concerns regarding toxicity. Our objective was to evaluate the safety and feasibility of establishing an adjuvant HAI program. METHODS: Patients who underwent HAI pump placement between January 2019 and February 2023 for CRLM were identified. Complications and HAI delivery were compared between patients who received HAI in the unresectable and adjuvant settings. RESULTS: Of 51 patients, 23 received HAI for unresectable CRLM and 28 in the adjuvant setting. Patients with unresectable CRLM more commonly had bilobar disease (n = 23/23 vs n = 18/28, p < 0.01) and more preoperative liver metastases (median 10 [IQR 6-15] vs 4 [IQR 3-7], p < 0.01). Biliary sclerosis was the most common complication (n = 2/23 vs n = 4/28); however, there were no differences in postoperative or HAI-specific complications. In the most recent two years, 0 patients in the unresectable group vs 2 patients in the adjuvant group developed biliary sclerosis. All patients were initiated on HAI with no difference in treatment times or dose reductions. CONCLUSION: Adjuvant HAI is safe and feasible for patients with resectable CRLM. HAI programs can carefully consider including patients with resectable CRLM if managed by an experienced multidisciplinary team with quality assurance controls in place.

Age effects on category learning, categorical perception, and generalization.

Age deficits in memory for individual episodes are well established. Less is known about how age affects another key memory function: the ability to form new conceptual knowledge. Here we studied age differences in concept formation in a category-learning paradigm with face-blend stimuli, using several metrics: direct learning of category members presented during training, generalisation of category labels to new examples, and shifts in perceived similarity between category members that often follow category learning. We found that older adults were impaired in direct learning of training examples, but that there was no significant age deficit in generalisation once we accounted for the deficit in direct learning. We also found that category learning affected the perceived similarity between members of the same versus opposing categories, and age did not significantly moderate this effect. Lastly, we compared traditional category learning to categorisation after a learning task in which a category label (shared last name) was presented alongside stimulus-specific information (unique first names that individuated category members). We found that simultaneously learning stimulus-specific and category information resulted in decreased category learning, and that this decrement was apparent in both age groups.

Impact of Pharmacist Involvement on the Utility of a Gram-Negative Blood Culture Identification Panel on Antimicrobial Usage.

Background: A rapid molecular diagnostic test (MDT) is a test used to identify several different species of gram-negative bacteria and their genetic resistance markers. However, the impact of rapid MDT has not been established when combined with pharmacist involvement. Objective: To determine the impact of pharmacy involvement on patient outcomes when using rapid MDT. The primary outcome is the time from gram stain result to the first dose of the targeted antibiotic. Methods: This is a single-center, quasi-experimental, 1-group pretest-posttest design study of patients with gram-negative bacteremia in a community hospital. Hospitalized patients 18 years or older were included if they had a gram-negative blood culture. Patients were excluded if they were discharged or expired prior to culture results. Outcomes were compared between patients prior to and after implementation of the automated MDT. This research was determined to be exempt from institutional review board oversight consistent with West Florida Healthcare and in accordance with institutional policy. Results: The use of rapid MDT combined with pharmacist intervention resulted in a statistically significant decrease in the time to targeted antibiotic therapy (pre-intervention group, n = 77, 44.8 ± 17.8 hours versus post-intervention group, n= 80, 4.4 ± 5.8 hours; P ≤.001). There was no significant difference found between secondary outcomes. Limitations included small sample size as well as inconsistent documentation. Conclusions: The use of rapid MDT combined with pharmacist intervention resulted in a statistically significant decrease in the time to targeted antibiotic therapy.

Sensory Representations Supporting Memory Specificity: Age Effects on Behavioral and Neural Discriminability.

Older adults' difficulty in distinguishing between old and new information contributes to memory decline, which may occur because older adults are less likely than young adults to retrieve specific sensory details necessary to distinguish between similar items. In male and female human subjects, the present study measured the extent of age differences in the specificity of memory representations using a false memory paradigm in which studied items were linked to retrieval items at multiple levels of similarity. Older adults showed poorer behavioral discrimination than young adults, driven primarily by false recognition of lures that differed from targets only in perceptual details. Patterns of activation across several regions within ventral visual cortex could be used to distinguish between targets and lures when they differed in both perceptual details and a semantic label. However, of ventral visual regions, only signals in the midline occipital cortex could be used to distinguish targets from lures when they differed only in perceptual details. Although there was an overall age deficit for this neural discrimination in this region, the positive relationship between neural and behavioral discriminability did not differ across age groups. In contrast, age moderated the relationship between neural and behavioral discriminability in lateral occipital and fusiform cortices, suggesting that activation patterns within these regions represent different types of information in each age group. Therefore, the quality of perceptual signals is a key contributor to memory discrimination across age groups, with evidence that age differences in the nature of representations emerges outside early visual cortex.SIGNIFICANCE STATEMENT Age-related memory decline is due in part to older adults' difficulties in discriminating between old and new information. We tested whether this deficit arises from lack of specificity in the sensory representations underlying older adults' recognition judgments. Using pattern classification analyses in ventral visual cortices, we found that signals in a region early in the visual stream could distinguish between targets and lures at the highest level of similarity. The discriminability of targets and lures in this region was positively related to behavioral discriminability across age groups despite an overall age deficit in classification accuracy. Together, results showed that older adults' memory deficits are related to reduced discriminability of cognitive processes (old/new recognition) in portions of visual cortex.

Generalization and the hippocampus: More than one story?

Memory-based cognition depends on both the ability to remember specific details of individual experiences and the ability to combine information across experiences to generalize and derive new knowledge. A hippocampal role in rapid encoding of specific events is long established. More recent research also demonstrates hippocampal contributions to generalization, but their nature is still debated. The current review provides an overview of hippocampal-based generalization in two lines of research-episodic inference and categorization-and discusses evidence for four candidate mechanisms and representational schemes that may underpin such generalization. We highlight evidence showing that the hippocampus contributes specific memories to generalization decisions, but also forms generalized representations that integrate information across experiences. Multiple views are currently plausible of how such generalized representations form and relate to specific memories. Future research that uses behavioral and neural indices of both generalization and specificity may help resolve between the candidate generalization mechanisms, with the possibility that more than one view of hippocampal-based generalization may be valid. Importantly, all views share the emphasis on the broader role of the hippocampus in cognition that goes beyond remembering the past.

Determination of the Optimal Procalcitonin Threshold for Infection in Patients With Impaired Renal Function at a Community Hospital.

Background: Procalcitonin (PCT) is a biomarker that can help identify bacterial infections but can be difficult to interpret in the presence of renal dysfunction, which can elevate PCT even in the absence of infection. Objective: To determine the optimal PCT threshold to identify infection in patients with renal dysfunction and pneumonia or sepsis. Methods: A retrospective analysis was performed for inpatients with creatinine clearance of ≤60 mL/min and PCT level from 2018 to 2019. A pharmacist blinded to study outcomes classified patients as infected or noninfected based on predetermined criteria. Receiver operating characteristic curve analysis was performed to establish the optimal PCT threshold overall, as well as in subgroups of patients with chronic kidney disease (CKD), acute kidney injury (AKI), and end-stage renal disease (ESRD). Institutional review board approval was obtained. Results: A total of 198 patients were included in the study (99 infected, 99 noninfected). The optimal threshold in the AKI, CKD, and ESRD subgroups was determined to be 1.5 ng/mL, 0.1 ng/mL, and 1.75 ng/mL, respectively. Conclusion: The results of this study show that PCT thresholds were specific to type of renal dysfunction. These results differ from the traditionally accepted PCT threshold of 0.5 ng/mL for sepsis and 0.25 mg/mL for pneumonia. Future studies should confirm the appropriate PCT threshold in ESRD and CKD patient populations.

Abstract Memory Representations in the Ventromedial Prefrontal Cortex and Hippocampus Support Concept Generalization.

Memory function involves both the ability to remember details of individual experiences and the ability to link information across events to create new knowledge. Prior research has identified the ventromedial prefrontal cortex (VMPFC) and the hippocampus as important for integrating across events in the service of generalization in episodic memory. The degree to which these memory integration mechanisms contribute to other forms of generalization, such as concept learning, is unclear. The present study used a concept-learning task in humans (both sexes) coupled with model-based fMRI to test whether VMPFC and hippocampus contribute to concept generalization, and whether they do so by maintaining specific category exemplars or abstract category representations. Two formal categorization models were fit to individual subject data: a prototype model that posits abstract category representations and an exemplar model that posits category representations based on individual category members. Latent variables from each of these models were entered into neuroimaging analyses to determine whether VMPFC and the hippocampus track prototype or exemplar information during concept generalization. Behavioral model fits indicated that almost three-quarters of the subjects relied on prototype information when making judgments about new category members. Paralleling prototype dominance in behavior, correlates of the prototype model were identified in VMPFC and the anterior hippocampus with no significant exemplar correlates. These results indicate that the VMPFC and portions of the hippocampus play a broad role in memory generalization and that they do so by representing abstract information integrated from multiple events.SIGNIFICANCE STATEMENT Whether people represent concepts as a set of individual category members or by deriving generalized concept representations abstracted across exemplars has been debated. In episodic memory, generalized memory representations have been shown to arise through integration across events supported by the ventromedial prefrontal cortex (VMPFC) and hippocampus. The current study combined formal categorization models with fMRI data analysis to show that the VMPFC and anterior hippocampus represent abstract prototype information during concept generalization, contributing novel evidence of generalized concept representations in the brain. Results indicate that VMPFC-hippocampal memory integration mechanisms contribute to knowledge generalization across multiple cognitive domains, with the degree of abstraction of memory representations varying along the long axis of the hippocampus.

Differential Functional Connectivity along the Long Axis of the Hippocampus Aligns with Differential Role in Memory Specificity and Generalization.

The hippocampus contributes to both remembering specific events and generalization across events. Recent work suggests that information may be represented along the longitudinal axis of the hippocampus at varied levels of specificity: detailed representations in the posterior hippocampus and generalized representations in the anterior hippocampus. Similar distinctions are thought to exist within neocortex, with lateral prefrontal and lateral parietal regions supporting memory specificity and ventromedial prefrontal and lateral temporal cortices supporting generalized memory. Here, we tested whether functional connectivity of anterior and posterior hippocampus with cortical memory regions is consistent with these proposed dissociations. We predicted greater connectivity of anterior hippocampus with putative generalization regions and posterior hippocampus with putative memory specificity regions. Furthermore, we tested whether differences in connectivity are stable under varying levels of task engagement. Participants learned to categorize a set of stimuli outside the scanner, followed by an fMRI session that included a rest scan, passive viewing runs, and category generalization task runs. Analyses revealed stronger connectivity of ventromedial pFC to anterior hippocampus and of angular gyrus and inferior frontal gyrus to posterior hippocampus. These differences remained relatively stable across the three phases (rest, passive viewing, category generalization). Whole-brain analyses further revealed widespread cortical connectivity with both anterior and posterior hippocampus, with relatively little overlap. These results contribute to our understanding of functional organization along the long axis of the hippocampus and suggest that distinct hippocampal-cortical connections are one mechanism by which the hippocampus represents both individual experiences and generalized knowledge.

Repeated study of items with and without repeated context: aging effects on memory discriminability.

Presenting items multiple times during encoding is a common way to enhance recognition accuracy. Under such conditions, older adults often show an increase in false recognition that counteracts benefits of repeated study. Using a false-memory paradigm with related study items and related lures, we tested whether repetition within the same encoding task or repetition across two different encoding tasks would be more beneficial to older adults' memory discriminability. Results showed that, compared to items not repeated at study, items repeated in the same context and items repeated across different contexts showed improvements in memory discriminability in both young and older adults. This improvement was primarily reflected in improved recollection responses for both age groups across both repeat study conditions, as compared to no repetition. Importantly, the results demonstrated that repetition can be used to successfully mitigate age-related deficits by increasing memory discriminability and without incurring a cost of false recognition specific to any one age group.

Modulation of target recollection and recollection rejection networks due to retrieval facilitation and interference.

To better understand neural recollection processing, we induced interference in target recollection by presenting related lures before their respective targets and facilitated recollection rejection of lures by presenting targets before their related lures. Target recollection following interference recruited visual and prefrontal cortices, showing that these regions support recollection when related information has disrupted target representations. Recollection rejection following target presentation recruited angular gyrus, indicating that this region supports recollection rejection when target representations are strong and highly accessible. Thus, recollection networks are sensitive to the accessibility of target representations that are affected by the presentation of related information during retrieval.

The Neural Basis of Recollection Rejection: Increases in Hippocampal-Prefrontal Connectivity in the Absence of a Shared Recall-to-Reject and Target Recollection Network.

Recollection rejection or "recall-to-reject" is a mechanism that has been posited to help maintain accurate memory by preventing the occurrence of false memories. Recollection rejection occurs when the presentation of a new item during recognition triggers recall of an associated target, a mismatch in features between the new and old items is registered, and the lure is correctly rejected. Critically, this characterization of recollection rejection involves a recall signal that is conceptually similar to recollection as elicited by a target. However, previous neuroimaging studies have not evaluated the extent to which recollection rejection and target recollection rely on a common neural signal but have instead focused on recollection rejection as a postretrieval monitoring process. This study utilized a false memory paradigm in conjunction with an adapted remember-know-new response paradigm that separated "new" responses based on recollection rejection from those that were based on a lack of familiarity with the item. This procedure allowed for parallel recollection rejection and target recollection contrasts to be computed. Results revealed that, contrary to predictions from theoretical and behavioral literature, there was virtually no evidence of a common retrieval mechanism supporting recollection rejection and target recollection. Instead of the typical target recollection network, recollection rejection recruited a network of lateral prefrontal and bilateral parietal regions that is consistent with the retrieval monitoring network identified in previous neuroimaging studies of recollection rejection. However, a functional connectivity analysis revealed a component of the frontoparietal rejection network that showed increased coupling with the right hippocampus during recollection rejection responses. As such, we demonstrate a possible link between PFC monitoring network and basic retrieval mechanisms within the hippocampus that was not revealed with univariate analyses alone.

The neural correlates of correctly rejecting lures during memory retrieval: the role of item relatedness.

Successful memory retrieval is predicated not only on recognizing old information, but also on correctly rejecting new information (lures) in order to avoid false memories. Correctly rejecting lures is more difficult when they are perceptually or semantically related to information presented at study as compared to when lures are distinct from previously studied information. This behavioral difference suggests that the cognitive and neural basis of correct rejections differs with respect to the relatedness between lures and studied items. The present study sought to identify neural activity that aids in suppressing false memories by examining the network of brain regions underlying correct rejection of related and unrelated lures. Results showed neural overlap in the right hippocampus and anterior parahippocampal gyrus associated with both related and unrelated correct rejections, indicating that some neural regions support correctly rejecting lures regardless of their semantic/perceptual characteristics. Direct comparisons between related and unrelated correct rejections showed that unrelated correct rejections were associated with greater activity in bilateral middle and inferior temporal cortices, regions that have been associated with categorical processing and semantic labels. Related correct rejections showed greater activation in visual and lateral prefrontal cortices, which have been associated with perceptual processing and retrieval monitoring. Thus, while related and unrelated correct rejections show some common neural correlates, related correct rejections are driven by greater perceptual processing whereas unrelated correct rejections show greater reliance on salient categorical cues to support quick and accurate memory decisions.

Coherent category training enhances generalization in prototype-based categories.

A major question for the study of learning and memory is how to tailor learning experiences to promote knowledge that generalizes to new situations. In two experiments, we used category learning as a representative domain to test two factors thought to influence the acquisition of conceptual knowledge: the number of training examples (set size) and the similarity of training examples to the category average (set coherence). Across participants, size and coherence of category training sets were varied in a fully crossed design. After training, participants demonstrated the breadth of their category knowledge by categorizing novel examples varying in their distance from the category center. Results showed better generalization following more coherent training sets, even when categorizing items furthest from the category center. Training set size had limited effects on performance. We also tested the types of representations underlying categorization decisions by fitting formal prototype and exemplar models. Prototype models posit abstract category representations based on the category's central tendency, whereas exemplar models posit that categories are represented by individual category members. In Experiment 1, low coherence training led to fewer participants relying on prototype representations, except when training length was extended. In Experiment 2, low coherence training led to chance performance and no clear representational strategy for nearly half of the participants. The results indicate that highlighting commonalities among exemplars during training facilitates learning and generalization and may also affect the types of concept representations that individuals form. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Learning new categories in older age: A review of theoretical perspectives and empirical findings.

The ability to learn new concepts involves linking pieces of related information to create an organized knowledge structure, and it is an essential cognitive function for individuals of all ages. Despite its importance, concept learning has received less attention in the field of cognitive aging compared to areas such as episodic memory and cognitive control, and there has yet to be a synthesis of age-related findings in this domain. In this review, we summarize the findings from empirical studies investigating age-related differences in categorization-a domain within concept learning that involves linking items to a shared label and allows for classification of novel members of the category. We focus on several hypotheses about what might drive age-related differences in categorization, including differences in perceptual clustering, the ability to form specific and generalized category representations, performance on tasks that are thought to recruit different memory systems, attention to stimulus features, and strategic and metacognitive processes. Overall, the existing literature suggests that older and younger adults may differ in the way they approach learning new categories, and this difference emerges across several different categorization tasks and category structures. We conclude by encouraging future research that takes advantage of the strong existing theoretical foundations in both the concept learning and cognitive aging domains. This approach has the potential to broaden our understanding of the factors that influence category formation across the adult lifespan and provide a more complete picture of age-related differences across multiple cognitive domains. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

True and phantom recollection: an fMRI investigation of similar and distinct neural correlates and connectivity.

Although research suggests that most false memories are mediated by a sense of familiarity, behavioral evidence indicates that some are characterized by retrieval of item-specific details associated with recollection. However, neuroimaging studies have yet to isolate and analyze the neural correlates of false (or phantom) recollection, focusing instead on general recognition processes. In doing so, results are mixed with respect to the role of the medial temporal lobes (MTL) in distinguishing between true and false retrieval. The present study sought to investigate the neural basis of true and phantom recollection and clarify the role of the MTL in dissociating between the two processes. Results showed that true and phantom recollection were associated with a largely overlapping retrieval network including activity in bilateral anterior parahippocampal gyrus, fusiform gyrus, anterior cingulate cortex, and right superior parietal cortex. However, connectivity analyses using two common MTL seeds revealed a more inferior network (fusiform gyrus, hippocampus, middle temporal gyrus) associated with true recollection and a more superior network (superior parietal, superior frontal gyrus, posterior cingulate cortex) associated with false recollection. Finally, direct comparisons between true and phantom recollection showed greater activity in right hippocampus and early visual cortex for true recollection, whereas no region exhibited greater activity for false recollection. Results indicate that while both true and phantom recollection show similar patterns of activation, there are also distinctions in the neural networks contributing to the two recollection processes. Moreover, results conclude that within the MTL, the hippocampus proper can distinguish between true and phantom recollection.

Age-related differences in encoding-retrieval similarity and their relationship to false memory.

Typical aging is associated with increases in false memory rates among older adults. Such errors are frequently associated with differential neural activity during encoding and retrieval in older compared to younger adults within visual cortices and the hippocampus. It remains unknown how pattern similarity reductions relate to false memories in healthy aging. Using encoding-retrieval similarity (ERS) analyses in a sample of younger and older adults, we examined how the similarity of neural patterns between memory phases associated with target and lure objects was impacted by age and contributed to false memory rates. Single-item ERS for targets and lures was reduced by age throughout much of the ventral visual stream and the posterior hippocampus. Furthermore, ERS associated with perceptual lures within the visual stream maintained differential relationships with false memory. Finally, a global ERS metric accounted for age deficits in single-item ERS, but did not contribute to false memory rates. These findings highlight the contribution of age-related reductions in ERS across multiple representational levels to false memories in healthy aging.

The effects of age on category learning and prototype- and exemplar-based generalization.

The need to learn new concepts and categories persists through the lifespan, yet little is known about how aging affects the concept learning and generalization. Here, we trained young and older adults to classify typical and boundary category members, and then tested category generalization to new stimuli. During training, older adults had increased difficulty compared to young adults learning category labels for boundary items, but not typical items. At test, categorization performance that included new items at all levels of typicality was comparable across age groups, but formal categorization models indicated that older adults relied to a greater degree on generalized (prototype) category representations than young adults. These findings align with the proposal that older adults are able to form category representations based on central tendency even when they have difficulty learning and remembering individual category members. More broadly, the results contribute to our understanding of multiple categorization strategies and the limited strategy flexibility in older adults. They also highlight how reliance on preserved cognitive functions may sometimes help older adults maintain performance. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Generalization and False Memory in an Acquired Equivalence Paradigm: The Influence of Physical Resemblance Across Related Episodes.

The ability to make inferences about related experiences is an important function of memory that allows individuals to build generalizable knowledge. In some cases, however, making inferences may lead to false memories when individuals misremember inferred information as having been observed. One factor that is known to increase the prevalence of false memories is the physical resemblance between new and old information. The extent to which physical resemblance has parallel effects on generalization and memory for the source of inferred associations is not known. To investigate the parallels between memory generalization and false memories, we conducted three experiments using an acquired equivalence paradigm and manipulated physical resemblance between items that made up related experiences. The three experiments showed increased generalization for higher levels of resemblance. Recognition and source memory judgments revealed that high rates of generalization were not always accompanied by high rates of false memories. Thus, physical resemblance across episodes may promote generalization with or without a trade-off in terms of impeding memory specificity.

Training set coherence and set size effects on concept generalization and recognition.

Building conceptual knowledge that generalizes to novel situations is a key function of human memory. Category-learning paradigms have long been used to understand the mechanisms of knowledge generalization. In the present study, we tested the conditions that promote formation of new concepts. Participants underwent 1 of 6 training conditions that differed in the number of examples per category (set size) and their relative similarity to the category average (set coherence). Performance metrics included rates of category learning, ability to generalize categories to new items of varying similarity to prototypes, and recognition memory for individual examples. In categorization, high set coherence led to faster learning and better generalization, while set size had little effect. Recognition did not differ reliably among conditions. We also tested the nature of memory representations used for categorization and recognition decisions using quantitative prototype and exemplar models fit to behavioral responses. Prototype models posit abstract category representations based on the category's central tendency, whereas exemplar models posit that categories are represented by individual category members. Prototype strategy use during categorization increased with increasing set coherence, suggesting that coherent training sets facilitate extraction of commonalities within a category. We conclude that learning from a coherent set of examples is an efficient means of forming abstract knowledge that generalizes broadly. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Tracking prototype and exemplar representations in the brain across learning.

There is a long-standing debate about whether categories are represented by individual category members (exemplars) or by the central tendency abstracted from individual members (prototypes). Neuroimaging studies have shown neural evidence for either exemplar representations or prototype representations, but not both. Presently, we asked whether it is possible for multiple types of category representations to exist within a single task. We designed a categorization task to promote both exemplar and prototype representations and tracked their formation across learning. We found only prototype correlates during the final test. However, interim tests interspersed throughout learning showed prototype and exemplar representations across distinct brain regions that aligned with previous studies: prototypes in ventromedial prefrontal cortex and anterior hippocampus and exemplars in inferior frontal gyrus and lateral parietal cortex. These findings indicate that, under the right circumstances, individuals may form representations at multiple levels of specificity, potentially facilitating a broad range of future decisions.