Early-life prefrontal cortex inhibition and early-life stress lead to long-lasting behavioral, transcriptional, and physiological impairments.

Early-life stress has been linked to multiple neurodevelopmental and neuropsychiatric deficits. Our previous studies have linked maternal presence/absence from the nest in developing rat pups to changes in prefrontal cortex (PFC) activity. Furthermore, we have shown that these changes are modulated by serotonergic signaling. Here we test whether changes in PFC activity during early life affect the developing cortex leading to behavioral alterations in the adult. We show that inhibiting the PFC of mouse pups leads to cognitive deficits in the adult comparable to those seen following maternal separation. Moreover, we show that activating the PFC during maternal separation can prevent these behavioral deficits. To test how maternal separation affects the transcriptional profile of the PFC we performed single-nucleus RNA-sequencing. Maternal separation led to differential gene expression almost exclusively in inhibitory neurons. Among others, we found changes in GABAergic and serotonergic pathways in these interneurons. Interestingly, both maternal separation and early-life PFC inhibition led to changes in physiological responses in prefrontal activity to GABAergic and serotonergic antagonists that were similar to the responses of more immature brains. Prefrontal activation during maternal separation prevented these changes. These data point to a crucial role of PFC activity during early life in behavioral expression in adulthood.

A tuberculosis elimination-focused geospatial approach to optimising access to diagnostic GeneXpert machines in Fiji.

OBJECTIVES: Fiji could be the first country to eliminate tuberculosis. To inform this strategy, we aimed to identify how many GeneXpert® machines are required to enable over 90% of Fijians to be within one-hour easy access. METHODS: We used Geographic Information System (Quantum GIS; QGIS), OpenStreetMap and population data (Kontur) to map possible facilities in relation to QGIS generated 60-min drive-time isochrones, with correction for missing road data. For outer islands, we calculated a distance to nearest hub operation. RESULTS: The solution comprised 24 GeneXpert® machines, allocating 7 GeneXpert® to Viti Levu, 6 GeneXpert® to Vanua Levu and 11 to other islands. This resulted in 827,810 people, 93.6% of Fiji's population, being within 1 h of a machine. Twenty-one thousand four hundred seventy-nine people on outer islands were an average of 43 km by water from the nearest facility. CONCLUSIONS: We conclude that over 90% of Fijians could be within an hour of a GeneXpert® machine with placement of 24 machines.

The human olfactory bulb processes odor valence representation and cues motor avoidance behavior.

Determining the valence of an odor to guide rapid approach-avoidance behavior is thought to be one of the core tasks of the olfactory system, and yet little is known of the initial neural mechanisms supporting this process or of its subsequent behavioral manifestation in humans. In two experiments, we measured the functional processing of odor valence perception in the human olfactory bulb (OB)-the first processing stage of the olfactory system-using a noninvasive method as well as assessed the subsequent motor avoidance response. We demonstrate that odor valence perception is associated with both gamma and beta activity in the human OB. Moreover, we show that negative, but not positive, odors initiate an early beta response in the OB, a response that is linked to a preparatory neural motor response in the motor cortex. Finally, in a separate experiment, we show that negative odors trigger a full-body motor avoidance response, manifested as a rapid leaning away from the odor, within the time period predicted by the OB results. Taken together, these results demonstrate that the human OB processes odor valence in a sequential manner in both the gamma and beta frequency bands and suggest that rapid processing of unpleasant odors in the OB might underlie rapid approach-avoidance decisions.

Rapid SARS-CoV-2 Seroprevalence Survey in Central and Western Divisions of Fiji, 2021.

During November-December 2021, we performed a SARS-CoV-2 seroprevalence survey in Central and Western Divisions of Fiji. A total of 539 participants 8-70 years of age were 95.5% (95% CI 93.4%-97.1%) seropositive, indicating high community levels of immunity. Seroprevalence studies can inform public health responses to emerging SARS-CoV-2 variants.

Anti-inflammatory Action of BT75, a Novel RARα Agonist, in Cultured Microglia and in an Experimental Mouse Model of Alzheimer's Disease.

BT75, a boron-containing retinoid, is a novel retinoic acid receptor (RAR)α agonist synthesized by our group. Previous studies indicated that activation of retinoic acid (RA) signaling may attenuate progression of Alzheimer's disease (AD). Presently, we aimed to examine the anti-inflammatory effect of BT75 and explore the possible mechanism using cultured cells and an AD mouse model. Pretreatment with BT75 (1-25 µM) suppressed the release of nitric oxide (NO) and IL-1ß in the culture medium of mouse microglial SIM-A9 cells activated by LPS. BMS195614, an RARα antagonist, partially blocked the inhibition of NO production by BT75. Moreover, BT75 attenuated phospho-Akt and phospho-NF-κB p65 expression augmented by LPS. In addition, BT75 elevated arginase 1, IL-10, and CD206, and inhibited inducible nitric oxide synthase (iNOS) and IL-6 formation in LPS-treated SIM-A9 cells, suggesting the promotion of M1-M2 microglial phenotypic polarization. C57BL/6 mice were injected intracerebroventricularly (icv) with streptozotocin (STZ) (3 mg/kg) to provide an AD-like mouse model. BT75 (5 mg/kg) or the vehicle was intraperitoneally (ip) injected to icv-STZ mice once a day for 3 weeks. Immunohistochemical analyses indicated that GFAP-positive cells and rod or amoeboid-like Iba1-positive cells, which increased in the hippocampal fimbria of icv-STZ mice, were reduced by BT75 treatment. Western blot results showed that BT75 decreased levels of neuronal nitric oxide synthase (nNOS), GFAP, and phosphorylated Tau, and increased levels of synaptophysin in the hippocampus of icv-STZ mice. BT75 may attenuate neuroinflammation by affecting the Akt/NF-κB pathway and microglial M1-M2 polarization in LPS-stimulated SIM-A9 cells. BT75 also reduced AD-like pathology including glial activation in the icv-STZ mice. Thus, BT75 may be a promising anti-inflammatory and neuroprotective agent worthy of further AD studies.

Outcome of primary mediastinal large B-cell lymphoma using R-CHOP: impact of a PET-adapted approach.

Cure rates for primary mediastinal large B-cell lymphoma (PMBCL) have improved with the integration of rituximab. However, the type of primary therapy and role of radiotherapy (RT) remains ill-defined. Herein, we evaluated the outcome of PMBCL primarily treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and the impact of an end-of-treatment (EOT) 18F-fluorodeoxyglucose positron emission tomography (PET) scan to guide consolidative RT. Patients ≥18 years of age with PMBCL treated with curative intent rituximab-chemotherapy were identified. Prior to 2005, patients were recommended to receive R-CHOP + RT (RT era). Beginning in 2005, EOT PET was used to guide RT and only those with a PET-positive scan received RT (PET era). In total, 159 patients were identified, 94% were treated with R-CHOP and 44% received RT (78% in RT era, 28% in PET era). The 5-year time to progression (TTP) and overall survival (OS) for the entire cohort were 80% and 89%, respectively, similar across treatment eras. Overall, 10% had refractory disease. In total, 113 patients had an EOT PET scan: 63% negative and 37% positive with a 5-year TTP of 90% vs 71% and 5-year OS of 97% vs 88%, respectively. For those with Deauville (D)-scored PET scans (n = 103), the 5-year TTP for PET-negative cases by Deauville criteria (D1-D3, DX) was 91%, with inferior outcomes for D5 vs D4 (5-year TTP 33% vs 87%, P = .0002). Outcomes for PMBCL treated with RCHOP are favorable and use of a PET-adapted approach reduces RT in the majority of patients. A small proportion have refractory disease and may benefit from an alternate treatment.

Biological constraints on configural odour mixture perception.

Animals, including humans, detect odours and use this information to behave efficiently in the environment. Frequently, odours consist of complex mixtures of odorants rather than single odorants, and mixtures are often perceived as configural wholes, i.e. as odour objects (e.g. food, partners). The biological rules governing this 'configural perception' (as opposed to the elemental perception of mixtures through their components) remain weakly understood. Here, we first review examples of configural mixture processing in diverse species involving species-specific biological signals. Then, we present the original hypothesis that at least certain mixtures can be processed configurally across species. Indeed, experiments conducted in human adults, newborn rabbits and, more recently, in rodents and honeybees show that these species process some mixtures in a remarkably similar fashion. Strikingly, a mixture AB (A, ethyl isobutyrate; B, ethyl maltol) induces configural processing in humans, who perceive a mixture odour quality (pineapple) distinct from the component qualities (A, strawberry; B, caramel). The same mixture is weakly configurally processed in rabbit neonates, which perceive a particular odour for the mixture in addition to the component odours. Mice and honeybees also perceive the AB mixture configurally, as they respond differently to the mixture compared with its components. Based on these results and others, including neurophysiological approaches, we propose that certain mixtures are convergently perceived across various species of vertebrates/invertebrates, possibly as a result of a similar anatomical organization of their olfactory systems and the common necessity to simplify the environment's chemical complexity in order to display adaptive behaviours.

Scaling-up food policies in the Pacific Islands: protocol for policy engagement and mixed methods evaluation of intervention implementation.

BACKGROUND: There is a crisis of non-communicable diseases (NCDs) in the Pacific Islands, and poor diets are a major contributor. The COVID-19 pandemic and resulting economic crisis will likely further exacerbate the burden on food systems. Pacific Island leaders have adopted a range of food policies and regulations to improve diets. This includes taxes and regulations on compositional standards for salt and sugar in foods or school food policies. Despite increasing evidence for the effectiveness of such policies globally, there is a lack of local context-specific evidence about how to implement them effectively in the Pacific. METHODS: Our 5-year collaborative project will test the feasibility and effectiveness of policy interventions to reduce salt and sugar consumption in Fiji and Samoa, and examine factors that support sustained implementation. We will engage government agencies and civil society in Fiji and Samoa, to support the design, implementation and monitoring of evidence-informed interventions. Specific objectives are to: (1) conduct policy landscape analysis to understand potential opportunities and challenges to strengthen policies for prevention of diet-related NCDs in Fiji and Samoa; (2) conduct repeat cross sectional surveys to measure dietary intake, food sources and diet-related biomarkers; (3) use Systems Thinking in Community Knowledge Exchange (STICKE) to strengthen implementation of policies to reduce salt and sugar consumption; (4) evaluate the impact, process and cost effectiveness of implementing these policies. Quantitative and qualitative data on outcomes and process will be analysed to assess impact and support scale-up of future interventions. DISCUSSION: The project will provide new evidence to support policy making, as well as developing a low-cost, high-tech, sustainable, scalable system for monitoring food consumption, the food supply and health-related outcomes.

During infant maltreatment, stress targets hippocampus, but stress with mother present targets amygdala and social behavior.

Infant maltreatment increases vulnerability to physical and mental disorders, yet specific mechanisms embedded within this complex infant experience that induce this vulnerability remain elusive. To define critical features of maltreatment-induced vulnerability, rat pups were reared from postnatal day 8 (PN8) with a maltreating mother, which produced amygdala and hippocampal deficits and decreased social behavior at PN13. Next, we deconstructed the maltreatment experience to reveal sufficient and necessary conditions to induce this phenotype. Social behavior and amygdala deficits (volume, neurogenesis, c-Fos, local field potential) required combined chronic high corticosterone and maternal presence (not maternal behavior). Hippocampal deficits were induced by chronic high corticosterone regardless of social context. Causation was shown by blocking corticosterone during maltreatment and suppressing amygdala activity during social behavior testing. These results highlight (1) that early life maltreatment initiates multiple pathways to pathology, each with distinct causal mechanisms and outcomes, and (2) the importance of social presence on brain development.

Odor identity can be extracted from the reciprocal connectivity between olfactory bulb and piriform cortex in humans.

Neuronal oscillations route external and internal information across brain regions. In the olfactory system, the two central nodes-the olfactory bulb (OB) and the piriform cortex (PC)-communicate with each other via neural oscillations to shape the olfactory percept. Communication between these nodes have been well characterized in non-human animals but less is known about their role in the human olfactory system. Using a recently developed and validated EEG-based method to extract signals from the OB and PC sources, we show in healthy human participants that there is a bottom-up information flow from the OB to the PC in the beta and gamma frequency bands, while top-down information from the PC to the OB is facilitated by delta and theta oscillations. Importantly, we demonstrate that there was enough information to decipher odor identity above chance from the low gamma in the OB-PC oscillatory circuit as early as 100 ms after odor onset. These data further our understanding of the critical role of bidirectional information flow in human sensory systems to produce perception. However, future studies are needed to determine what specific odor information is extracted and communicated in the information exchange.

How do Pacific Island countries add up on contraception, abortion and reproductive coercion? Guidance from the Guttmacher report on investing in sexual and reproductive health.

The Guttmacher-Lancet Commission report on Sexual and Reproductive Health and Rights called for the acceleration of progress to achieve SRHR that is essential for sustainable development. To integrate the essential services defined in this report into universal health coverage in the 11 sovereign nations in the Pacific, quality data is required to ensure needs are met efficiently and equitably. However, there are no comprehensive reports for Pacific Island countries that provide insight into all areas of SRHR. We collated the latest literature to identify the most up-to-date relevant data from United Nations and Guttmacher Institute reports to discern gaps in SRHR information and services relating to contraception, abortion and reproductive coercion. Investment is urgently required to strengthen health information systems for SRHR in the Pacific.

Interaction Between Odor Identification Deficit and APOE4 Predicts 6-Year Cognitive Decline in Elderly Individuals.

Olfactory identification impairment might indicate future cognitive decline in elderly individuals. An unresolved question is to what extent this effect is dependent on the ApoE-ε4, a genotype associated with risk of Alzheimer's Disease (AD). Given the current concern about reproducibility in empirical research, we assessed this issue in a large sample (n = 1637) of older adults (60 - 96 years) from the population-based longitudinal Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). A hierarchical regression analysis was carried out to determine if a low score on an odor identification test, and the presence of ApoE-ε4, would predict the magnitude of a prospective 6-year change in the Mini-Mental State Examination (MMSE) after controlling for demographic, health-related, and cognitive variables. We found that overall, lower odor identification performance was predictive of cognitive decline, and, as hypothesized, we found that the effect was most pronounced among ApoE-ε4 carriers. Our results from this high-powered sample suggest that in elderly carriers of the ApoE-ε4 allele, odor identification impairment provides an indication of future cognitive decline, which has relevance for the prognosis of AD.

Neonatal Ethanol Disturbs the Normal Maturation of Parvalbumin Interneurons Surrounded by Subsets of Perineuronal Nets in the Cerebral Cortex: Partial Reversal by Lithium.

Reduction in parvalbumin-positive (PV+) interneurons is observed in adult mice exposed to ethanol at postnatal day 7 (P7), a late gestation fetal alcohol spectrum disorder model. To evaluate whether PV+ cells are lost, or PV expression is reduced, we quantified PV+ and associated perineuronal net (PNN)+ cell densities in barrel cortex. While PNN+ cell density was not reduced by P7 ethanol, PV cell density decreased by 25% at P90 with no decrease at P14. PNN+ cells in controls were virtually all PV+, whereas more than 20% lacked PV in ethanol-treated adult animals. P7 ethanol caused immediate apoptosis in 10% of GFP+ cells in G42 mice, which express GFP in a subset of PV+ cells, and GFP+ cell density decreased by 60% at P90 without reduction at P14. The ethanol effect on PV+ cell density was attenuated by lithium treatment at P7 or at P14-28. Thus, reduced PV+ cell density may be caused by disrupted cell maturation, in addition to acute apoptosis. This effect may be regionally specific: in the dentate gyrus, P7 ethanol reduced PV+ cell density by 70% at P14 and both PV+ and PNN+ cell densities by 50% at P90, and delayed lithium did not alleviate ethanol's effect.

The Value of Homework: Exposure to Odors in the Home Cage Enhances Odor-Discrimination Learning in Mice.

Perceptual learning is an enhancement in discriminability of similar stimuli following experience with those stimuli. Here, we examined the efficacy of adding additional active training following a standard training session, compared with additional stimulus exposure in the absence of associated task performance. Mice were trained daily in an odor-discrimination task, and then, several hours later each day, received 1 of 3 different manipulations: 1) a second active-training session, 2) non-task-related odor exposure in the home cage, or 3) no second session. For home-cage exposure, odorants were presented in small tubes that mice could sniff and investigate for a similar period of time as in the active discrimination task each day. The results demonstrate that daily home-cage exposure was equivalent to active odor training in supporting improved odor discrimination. Daily home-cage exposure to odorants that did not match those used in the active task did not improve learning, yielding outcomes similar to those obtained with no second session. Piriform cortical local field potential recordings revealed that both sampling in the active learning task and investigation in the home cage evoked similar beta band oscillatory activity. Together the results suggest that odor-discrimination learning can be significantly enhanced by addition of odor exposure outside of the active training task, potentially because of the robust activity evoked in the olfactory system by both exposure paradigms. They further suggest that odorant exposure alone could enhance or maintain odor-discrimination abilities in conditions associated with olfactory impairment, such as aging or dementia.

Developing a neurobehavioral animal model of poverty: Drawing cross-species connections between environments of scarcity-adversity, parenting quality, and infant outcome.

Children reared in impoverished environments are at risk for enduring psychological and physical health problems. Mechanisms by which poverty affects development, however, remain unclear. To explore one potential mechanism of poverty's impact on social-emotional and cognitive development, an experimental examination of a rodent model of scarcity-adversity was conducted and compared to results from a longitudinal study of human infants and families followed from birth (N = 1,292) who faced high levels of poverty-related scarcity-adversity. Cross-species results supported the hypothesis that altered caregiving is one pathway by which poverty adversely impacts development. Rodent mothers assigned to the scarcity-adversity condition exhibited decreased sensitive parenting and increased negative parenting relative to mothers assigned to the control condition. Furthermore, scarcity-adversity reared pups exhibited decreased developmental competence as indicated by disrupted nipple attachment, distress vocalization when in physical contact with an anesthetized mother, and reduced preference for maternal odor with corresponding changes in brain activation. Human results indicated that scarcity-adversity was inversely correlated with sensitive parenting and positively correlated with negative parenting, and that parenting fully mediated the association of poverty-related risk with infant indicators of developmental competence. Findings are discussed from the perspective of the usefulness of bidirectional-translational research to inform interventions for at-risk families.

Neural Representation of Odor-Guided Behavior in the Rat Olfactory Thalamus.

UNLABELLED: The mediodorsal thalamus (MDT) is a higher-order corticocortical thalamic nucleus involved in cognition and memory. However, anatomically, the MDT is also the primary site of olfactory representation in the thalamus, receiving strong inputs from olfactory cortex and having reciprocal connections with orbitofrontal cortex (OFC). Nonetheless, its role in olfaction remains unclear. Here, we recorded single units in the MDT, as well as local field potentials in the MDT, piriform cortex (PCX), and OFC in rats performing a two-alternative odor discrimination task. We show that subsets of MDT units display odorant selectivity during sampling, as well as encoding of spatio-motor aspects of the task. Furthermore, the olfactory trans-thalamic network rapidly switches functional connectivity between MDT and cortical areas depending on current task demands, with, for example, MDT-PCX coupling enhanced during odor sampling and MDT-OFC coupling enhanced during the decision/goal approach compared with baseline and presampling. These results demonstrate MDT representation of diverse sensorimotor components of an olfactory task. SIGNIFICANCE STATEMENT: The mediodorsal thalamus (MDT) is the major olfactory thalamic nucleus and links the olfactory archicortex with the prefrontal neocortex. The MDT is well known to be involved in higher-order cognitive and memory functions, but its role in olfaction is poorly understood. Here, using single-unit and local field potential analyses, we explored MDT function during an odor-guided decision task in rats. We describe MDT odor and multisensory coding and demonstrate behavior-dependent functional connectivity within the MDT/sensory cortex/prefrontal cortex network. Our results suggest a rich representation of olfactory and other information within MDT required to perform this odor-guided task. Our work opens a new model system for understanding MDT function and exploring the important role of MDT in cortical-cortical communication.

Development of Odor Hedonics: Experience-Dependent Ontogeny of Circuits Supporting Maternal and Predator Odor Responses in Rats.

UNLABELLED: A major component of perception is hedonic valence: perceiving stimuli as pleasant or unpleasant. Here, we used early olfactory experiences that shape odor preferences and aversions to explore developmental plasticity in circuits mediating odor hedonics. We used 2-deoxyglucose autoradiographic mapping of neural activity to identify circuits differentially activated by biologically relevant preferred and avoided odors across rat development. We then further probed this system by increasing or decreasing hedonic value. Using both region of interest and functional connectivity analyses, we identified regions within primary olfactory, amygdala/hippocampal, and prefrontal cortical networks that were activated differentially by maternal and male odors. Although some activated regions remained stable across development (postnatal days 7-23), there was a developmental emergence of others that resulted in an age-dependent elaboration of hedonic-response-specific circuitry despite stable behavioral responses (approach/avoidance) to the odors across age. Hedonic responses to these biologically important odors were modified through diet suppression of the maternal odor and co-rearing with a male. This allowed assessment of hedonic circuits in isolation of the specific odor quality and/or intensity. Early experience significantly modified odor-evoked circuitry in an age-dependent manner. For example, co-rearing with a male, which induced pup attraction to male odor, reduced activity in amygdala regions normally activated by the unfamiliar avoided male odor, making this region more consistent with maternal odor. Understanding the development of odor hedonics, particularly within the context of altered early life experience, provides insight into the development of sensory processes, food preferences, and the formation of social affiliations, among other behaviors. SIGNIFICANCE STATEMENT: Odor hedonic valence controls approach-avoidance behaviors, but also modulates ongoing behaviors ranging from food preferences and social affiliation with the caregiver to avoidance of predator odors. Experiences can shape hedonic valence. This study explored brain circuitry involved in odor hedonic encoding throughout development using maternal and predator odors and assessed the effects of early life experience on odor hedonic encoding by increasing/decreasing the hedonic value of these odors. Understanding the role of changing brain circuitry during development and its impact on behavioral function is critical for understanding sensory processing across development. These data converge with exciting literature on the brain's hedonic network and highlight the significant role of early life experience in shaping the neural networks of highly biologically relevant stimuli.

Default mode network deactivation during odor-visual association.

Default mode network (DMN) deactivation has been shown to be functionally relevant for goal-directed cognition. In this study, the DMN's role during olfactory processing was investigated using two complementary functional magnetic resonance imaging (fMRI) paradigms with identical timing, visual-cue stimulation, and response monitoring protocols. Twenty-nine healthy, non-smoking, right-handed adults (mean age = 26 ± 4 years, 16 females) completed an odor-visual association fMRI paradigm that had two alternating odor + visual and visual-only trial conditions. During odor + visual trials, a visual cue was presented simultaneously with an odor, while during visual-only trial conditions the same visual cue was presented alone. Eighteen of the twenty-nine participants (mean age = 27.0 ± 6.0 years, 11 females) also took part in a control no-odor fMRI paradigm that consisted of a visual-only trial condition which was identical to the visual-only trials in the odor-visual association paradigm. Independent Component Analysis (ICA), extended unified structural equation modeling (euSEM), and psychophysiological interaction (PPI) were used to investigate the interplay between the DMN and olfactory network. In the odor-visual association paradigm, DMN deactivation was evoked by both the odor + visual and visual-only trial conditions. In contrast, the visual-only trials in the no-odor paradigm did not evoke consistent DMN deactivation. In the odor-visual association paradigm, the euSEM and PPI analyses identified a directed connectivity between the DMN and olfactory network which was significantly different between odor + visual and visual-only trial conditions. The results support a strong interaction between the DMN and olfactory network and highlights the DMN's role in task-evoked brain activity and behavioral responses during olfactory processing. Hum Brain Mapp 38:1125-1139, 2017. © 2016 Wiley Periodicals, Inc.

The Olfactory Mosaic: Bringing an Olfactory Network Together for Odor Perception.

Olfactory perception and its underlying neural mechanisms are not fixed, but rather vary over time, dependent on various parameters such as state, task, or learning experience. In olfaction, one of the primary sensory areas beyond the olfactory bulb is the piriform cortex. Due to an increasing number of functions attributed to the piriform cortex, it has been argued to be an associative cortex rather than a simple primary sensory cortex. In fact, the piriform cortex plays a key role in creating olfactory percepts, helping to form configural odor objects from the molecular features extracted in the nose. Moreover, its dynamic interactions with other olfactory and nonolfactory areas are also critical in shaping the olfactory percept and resulting behavioral responses. In this brief review, we will describe the key role of the piriform cortex in the larger olfactory perceptual network, some of the many actors of this network, and the importance of the dynamic interactions among the piriform-trans-thalamic and limbic pathways.

Unexplained Obstruction of an Integrated Cardiotomy Filter During Cardiopulmonary Bypass.

Cardiopulmonary bypass (CPB) is considered relatively safe in most cases, yet is not complication free. We present a case of an integrated cardiotomy filter obstruction during CPB, requiring circuit reconfiguration. Approximately an hour after uneventful initiation of CPB the integrated cardiotomy filter became obstructed over several minutes, requiring circuit reconfiguration using an external cardiotomy filter to maintain functionality. Following reconfiguration, CPB was maintained with a fully functional circuit allowing safe patient support throughout the remainder of CPB. Postoperatively, there was no sign of thrombus or mechanical obstruction of the filter, which was sent to the manufacturer for analysis. The cause of the obstruction was unclear even after chemical analysis, visual inspection, and a review of all techniques and products to which the patient was exposed. The patient had a generally routine hospital stay, with no signs or symptoms related to the incident. To our knowledge, this is the first report describing an obstructed integrated cardiotomy filter. An appropriate readiness plan for such an incident includes proper venting of the filter chamber, a method for detecting an obstruction, and a plan for circuit reconfiguration. This case illustrates the need for a formal reporting structure for incidents or "near miss" incidents during CPB.