Real world management of individuals with severe FXI deficiency and its impact on clinical outcomes: Experience from a haemophilia treatment centre.

INTRODUCTION: The management of Factor XI deficiency is challenged by a variable association between FXI level and bleeding phenotype. Additionally, there is scarce data describing management strategies and their outcomes, specifically bleeding, thrombosis, and other complications. AIMS: To evaluate bleeding, thrombosis, and other complications in individuals with severe FXI deficiency seen in our comprehensive haemophilia treatment centre (HTC). Peri-procedural management strategies and the resulting impact on bleeding and other clinically relevant outcomes were reported. METHODS: Retrospective review of the electronic medical record of adult patients with severe FXI deficiency (< 20% activity) seen at a New York City comprehensive HTC between 2017 and 2022. Procedures, haemostatic management, and outcomes were collected and analysed. RESULTS: We identified 38 individuals (64%) females with severe FXI deficiency. The mean age was 56 ± 21 years (SD). The median FXI activity level was 3% (IQR: 1-8%). The mean BAT score was 3.1 ± 2.4; (52%) individuals did not have a history of bleeding. A total of 256 surgeries and procedures were performed. There was reduced bleeding with preventative or reactive treatment during procedures. Arterial but not venous thrombotic complications were observed. Plasma was mostly used for procedures associated with higher risk of bleeding and antifibrinolytics for procedures at sites of high fibrinolysis. CONCLUSIONS: Current management strategies pose a burden of care for these patients and manifested as nonbleeding adverse events and changes in clinical management. These findings highlight the need for novel investigation in predicting and managing bleeding for individuals with severe FXI deficiency.

Ocular following responses of the marmoset monkey are dependent on postsaccadic delay, spatiotemporal frequency, and saccade direction.

Ocular following is a short-latency, reflexive eye movement that tracks wide-field visual motion. It has been studied extensively in humans and macaques and is an appealing behavior for studying sensory-motor transformations in the brain because of its rapidity and rigidity. We explored ocular following in the marmoset, an emerging model in neuroscience because their lissencephalic brain allows direct access to most cortical areas for imaging and electrophysiological recordings. In three experiments, we tested ocular following responses in three adult marmosets. First, we varied the delay between saccade end and stimulus motion onset, from 10 to 300 ms. As in other species, tracking had shorter onset latencies and higher eye speeds with shorter postsaccadic delays. Second, using sine-wave grating stimuli, we explored the dependence of eye speed on spatiotemporal frequency. The highest eye speed was evoked at ∼16 Hz and ∼0.16 cycles per degree (cpd); however, the highest gain was elicited at ∼1.6 Hz and ∼1.2 cpd. The highest eye speed for each spatial frequency was observed at a different temporal frequency, but this interdependence was not consistent with complete speed tuning of the ocular following response. Finally, we found the highest eye speeds when saccade and stimulus motion directions were identical, although latencies were unaffected by direction difference. Our results showed qualitatively similar ocular following in marmosets, humans, and macaques, despite over an order of magnitude variation in body and eye size across species. This characterization will help future studies examining the neural basis of sensory-motor transformations.NEW & NOTEWORTHY Previous ocular following studies focused on humans and macaques. We examined the properties of ocular following responses in marmosets in three experiments, in which postsaccadic delay, spatial-temporal frequency of stimuli, and congruence of saccade and motion directions were manipulated. We have demonstrated short-latency ocular following in marmosets and discuss the similarities across three species that vary markedly in eye and head size. Our findings will help future studies examining the neural mechanism of sensory-motor transformations.

Real-world effectiveness of steroids in severe COVID-19: a retrospective cohort study.

INTRODUCTION: Randomised controlled trials have shown that steroids reduce the risk of dying in patients with severe Coronavirus disease 2019 (COVID-19), whilst many real-world studies have failed to replicate this result. We aim to investigate real-world effectiveness of steroids in severe COVID-19. METHODS: Clinical, demographic, and viral genome data extracted from electronic patient record (EPR) was analysed from all SARS-CoV-2 RNA positive patients admitted with severe COVID-19, defined by hypoxia at presentation, between March 13th 2020 and May 27th 2021. Steroid treatment was measured by the number of prescription-days with dexamethasone, hydrocortisone, prednisolone or methylprednisolone. The association between steroid > 3 days treatment and disease outcome was explored using multivariable cox proportional hazards models with adjustment for confounders (including age, gender, ethnicity, co-morbidities and SARS-CoV-2 variant). The outcome was in-hospital mortality. RESULTS: 1100 severe COVID-19 cases were identified having crude hospital mortality of 15.3%. 793/1100 (72.1%) individuals were treated with steroids and 513/1100 (46.6%) received steroid ≤ 3 days. From the multivariate model, steroid > 3 days was associated with decreased hazard of in-hospital mortality (HR: 0.47 (95% CI: 0.31-0.72)). CONCLUSION: The protective effect of steroid treatment for severe COVID-19 reported in randomised clinical trials was replicated in this retrospective study of a large real-world cohort.

Insulinoma-derived pseudo-islets for diabetes research.

The islets of Langerhans of the pancreas are the primary endocrine organ responsible for regulating whole body glucose homeostasis. The use of isolated primary islets for research development and training requires organ resection, careful digestion, and isolation of the islets from nonendocrine tissue. This process is time consuming, expensive, and requires substantial expertise. For these reasons, we sought to develop a more rapidly obtainable and consistent model system with characteristic islet morphology and function that could be employed to train personnel and better inform experiments prior to using isolated rodent and human islets. Immortalized ß cell lines reflect several aspects of primary ß cells, but cell propagation in monolayer cell culture limits their usefulness in several areas of research, which depend on islet morphology and/or functional assessment. In this manuscript, we describe the propagation and characterization of insulinoma pseudo-islets (IPIs) from a rat insulinoma cell line INS832/3. IPIs were generated with an average diameter of 200 µm, consistent with general islet morphology. The rates of oxygen consumption and mitochondrial oxidation-reduction changes in response to glucose and metabolic modulators were similar to isolated rat islets. In addition, the dynamic insulin secretory patterns of IPIs were similar to primary rat islets. Thus, INS832/3-derived IPIs provide a valuable and convenient model for accelerating islet and diabetes research.

Visual responses in the dorsolateral frontal cortex of marmoset monkeys.

The marmoset monkey (Callithrix jacchus) has gained attention in neurophysiology research as a new primate model for visual processing and behavior. In particular, marmosets have a lissencephalic cortex, making multielectrode, optogenetic, and calcium-imaging techniques more accessible than other primate models. However, the degree of homology of brain circuits for visual behavior with those identified in macaques and humans is still being ascertained. For example, whereas the location of the frontal eye fields (FEF) within the dorsolateral frontal cortex has been proposed, it remains unclear whether neurons in the corresponding areas show visual responses-an important characteristic of FEF neurons in other species. Here, we provide the first description of receptive field properties and neural response latencies in the marmoset dorsolateral frontal cortex, based on recordings using Utah arrays in anesthetized animals. We find brisk visual responses in specific regions of the dorsolateral prefrontal cortex, particularly in areas 8aV, 8C, and 6DR. As in macaque FEF, the receptive fields were typically large (10°-30° in diameter) and the median responses latency was brisk (60 ms). These results constrain the possible interpretations about the location of the marmoset FEF and suggest that the marmoset model's significant advantages for the use of physiological techniques may be leveraged in the study of visuomotor cognition.NEW & NOTEWORTHY Behavior and cognition in humans and other primates rely on networks of brain areas guided by the frontal cortex. The marmoset offers exciting new opportunities to study links between brain physiology and behavior, but the functions of frontal cortex areas are still being identified in this species. Here, we provide the first evidence of visual receptive fields in the marmoset dorsolateral frontal cortex, an important step toward future studies of visual cognitive behavior.

Combining population genomics and fitness QTLs to identify the genetics of local adaptation in Arabidopsis thaliana.

Evidence for adaptation to different climates in the model species Arabidopsis thaliana is seen in reciprocal transplant experiments, but the genetic basis of this adaptation remains poorly understood. Field-based quantitative trait locus (QTL) studies provide direct but low-resolution evidence for the genetic basis of local adaptation. Using high-resolution population genomic approaches, we examine local adaptation along previously identified genetic trade-off (GT) and conditionally neutral (CN) QTLs for fitness between locally adapted Italian and Swedish A. thaliana populations [Ågren J, et al. (2013) Proc Natl Acad Sci USA 110:21077-21082]. We find that genomic regions enriched in high FST SNPs colocalize with GT QTL peaks. Many of these high FST regions also colocalize with regions enriched for SNPs significantly correlated to climate in Eurasia and evidence of recent selective sweeps in Sweden. Examining unfolded site frequency spectra across genes containing high FST SNPs suggests GTs may be due to more recent adaptation in Sweden than Italy. Finally, we collapse a list of thousands of genes spanning GT QTLs to 42 genes that likely underlie the observed GTs and explore potential biological processes driving these trade-offs, from protein phosphorylation, to seed dormancy and longevity. Our analyses link population genomic analyses and field-based QTL studies of local adaptation, and emphasize that GTs play an important role in the process of local adaptation.

Correlated Variability in the Neurons With the Strongest Tuning Improves Direction Coding.

Sensory perception depends on neuronal populations creating an accurate representation of the external world. The amount of information that a population can represent depends on the tuning of individual neurons and the trial-by-trial variability shared among neurons. Although on average, pairwise spike-count correlations between neurons are positive, the distribution is wide, and the relationship between correlations and encoding is not straightforward. Here, we examine how single-neuron and population-level factors impact the efficacy of the neural code. We recorded responses to moving visual stimuli from motion-sensitive neurons in the middle temporal area of anesthetized marmosets (Callithrix jacchus) and trained decoders to assess how correlated and uncorrelated populations encoded stimulus motion direction. We found that the most responsive, direction-selective, and least variable neurons are the most relied-upon neurons in an uncorrelated population. In correlated populations, the same neurons do the most to shape the shared variability across the population in a way that facilitates decoding, and decoding is improved by the presence of temporally stable correlations. This suggests that the least variable neurons with the strongest stimulus representations enhance the population code by providing a strong signal and shaping correlations in variability orthogonally to the locus defined by the mean response.

Weighting neurons by selectivity produces near-optimal population codes.

Perception is produced by "reading out" the representation of a sensory stimulus contained in the activity of a population of neurons. To examine experimentally how populations code information, a common approach is to decode a linearly weighted sum of the neurons' spike counts. This approach is popular because of the biological plausibility of weighted, nonlinear integration. For neurons recorded in vivo, weights are highly variable when derived through optimization methods, but it is unclear how the variability affects decoding performance in practice. To address this, we recorded from neurons in the middle temporal area (MT) of anesthetized marmosets (Callithrix jacchus) viewing stimuli comprising a sheet of dots that moved coherently in 1 of 12 different directions. We found that high peak response and direction selectivity both predicted that a neuron would be weighted more highly in an optimized decoding model. Although learned weights differed markedly from weights chosen according to a priori rules based on a neuron's tuning profile, decoding performance was only marginally better for the learned weights. In the models with a priori rules, selectivity is the best predictor of weighting, and defining weights according to a neuron's preferred direction and selectivity improves decoding performance to very near the maximum level possible, as defined by the learned weights. NEW & NOTEWORTHY We examined which aspects of a neuron's tuning account for its contribution to sensory coding. Strongly direction-selective neurons are weighted most highly by optimal decoders trained to discriminate motion direction. Models with predefined decoding weights demonstrate that this weighting scheme causally improved direction representation by a neuronal population. Optimizing decoders (using a generalized linear model or Fisher's linear discriminant) led to only marginally better performance than decoders based purely on a neuron's preferred direction and selectivity.

Streptococcus pneumoniae as a Cause of Mycotic and Infected Aneurysms in Patients without Respiratory Features: Challenging Diagnoses Aided by 16S PCR.

BACKGROUND: Streptococcus pneumoniae is considered a rare cause of mycotic aneurysms. The microbiological diagnosis of mycotic aneurysms can be difficult, and many patients have negative blood culture results. METHODS: We describe a series of four consecutive cases of mycotic aneurysms caused by S. pneumoniae with no respiratory features or extravascular septic foci. In two patients with negative blood culture results, 16S PCR was used for the diagnosis of S. pneumoniae infection. RESULTS: Four men with mycotic aneurysms affecting the aorta, axillary, and popliteal arteries caused by S. pneumoniae presented to our center between 2015 and 2016. All were treated with at least one month of intravenous antibiotics, followed by at least 4 weeks of oral antibiotics. Two were additionally managed using endovascular surgical techniques, and one underwent an open surgical repair. The fourth patient presented with bilateral popliteal aneurysms, one of which ruptured and was managed using surgical ligation and bypass, whereas the other side subsequently ruptured and was repaired endovascularly. Three of the four patients are currently off antibiotics and considered cured, while one died of an unrelated cause. CONCLUSIONS: S. pneumoniae should be considered a potential causative agent of mycotic aneurysms. Diagnosis can be confirmed using 16S PCR, especially in patients where peripheral blood cultures are uninformative.

In vitro characterization of neonatal, juvenile, and adult porcine islet oxygen demand, ß-cell function, and transcriptomes.

BACKGROUND: There is currently a shortage of human donor pancreata which limits the broad application of islet transplantation as a treatment for type 1 diabetes. Porcine islets have demonstrated potential as an alternative source, but a study evaluating islets from different donor ages under unified protocols has yet to be conducted. METHODS: Neonatal porcine islets (NPI; 1-3 days), juvenile porcine islets (JPI; 18-21 days), and adult porcine islets (API; 2+ years) were compared in vitro, including assessments of oxygen consumption rate, membrane integrity determined by FDA/PI staining, ß-cell proliferation, dynamic glucose-stimulated insulin secretion, and RNA sequencing. RESULTS: Oxygen consumption rate normalized to DNA was not significantly different between ages. Membrane integrity was age dependent, and API had the highest percentage of intact cells. API also had the highest glucose-stimulated insulin secretion response during a dynamic insulin secretion assay and had 50-fold higher total insulin content compared to NPI and JPI. NPI and JPI had similar glucose responsiveness, ß-cell percentage, and ß-cell proliferation rate. Transcriptome analysis was consistent with physiological assessments. API transcriptomes were enriched for cellular metabolic and insulin secretory pathways, while NPI exhibited higher expression of genes associated with proliferation. CONCLUSIONS: The oxygen demand, membrane integrity, ß-cell function and proliferation, and transcriptomes of islets from API, JPI, and NPI provide a comprehensive physiological comparison for future studies. These assessments will inform the optimal application of each age of porcine islet to expand the availability of islet transplantation.

Rapid Adaptation Induces Persistent Biases in Population Codes for Visual Motion.

Each visual experience changes the neural response to subsequent stimuli. If the brain is unable to incorporate these encoding changes, the decoding, or perception, of subsequent stimuli is biased. Although the phenomenon of adaptation pervades the nervous system, its effects have been studied mainly in isolation, based on neuronal encoding changes induced by an isolated, prolonged stimulus. To understand how adaptation-induced biases arise and persist under continuous, naturalistic stimulation, we simultaneously recorded the responses of up to 61 neurons in the marmoset (Callithrix jacchus) middle temporal area to a sequence of directions that changed every 500 ms. We found that direction-specific adaptation following only 0.5 s of stimulation strongly affected encoding for up to 2 s by reducing both the gain and the spike count correlations between pairs of neurons with preferred directions close to the adapting direction. In addition, smaller changes in bandwidth and preferred direction were observed in some animals. Decoding individual trials of adaptation-affected activity in simultaneously recorded neurons predicted repulsive biases that are consistent with the direction aftereffect. Surprisingly, removing spike count correlations by trial shuffling did not impact decoding performance or bias. When adaptation had the largest effect on encoding, the decoder made the most errors. This suggests that neural and perceptual repulsion is not a mechanism to enhance perceptual performance but is instead a necessary consequence of optimizing neural encoding for the identification of a wide range of stimulus properties in diverse temporal contexts. SIGNIFICANCE STATEMENT: Although perception depends upon decoding the pattern of activity across a neuronal population, the encoding properties of individual neurons are unreliable: a single neuron's response to repetitions of the same stimulus is variable, and depends on both its spatial and temporal context. In this manuscript, we describe the complete cascade of adaptation-induced effects in sensory encoding and show how they predict population decoding errors consistent with perceptual biases. We measure the time course of adaptation-induced changes to the response properties of neurons in isolation, and to the correlation structure across pairs of simultaneously recorded neurons. These results provide novel insight into how and for how long adaptation affects the neural code, particularly during continuous, naturalistic vision.

Sensitivity of neurons in the middle temporal area of marmoset monkeys to random dot motion.

Neurons in the middle temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of "neurometric" thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide-anesthetized marmoset monkeys, a species that has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was the most effective predictor of neurometric threshold, whereas the direction tuning bandwidth had no correlation with the threshold. We also showed that it is possible to obtain reliable estimates of neurometric thresholds using stimuli that were not highly optimized for each neuron, as is often necessary when recording from large populations of neurons with different receptive field concurrently, as was the case in this study. These results demonstrate that marmoset MT shows an essential physiological similarity to macaque MT and suggest that its neurons are capable of representing motion signals that allow for comparable motion-in-noise judgments.NEW & NOTEWORTHY We report the activity of neurons in marmoset MT in response to random-dot motion stimuli of varying coherence. The information carried by individual MT neurons was comparable to that of the macaque, and the maximum firing rates were a strong predictor of sensitivity. Our study provides key information regarding the neural basis of motion perception in the marmoset, a small primate species that is becoming increasingly popular as an experimental model.

Masking reduces orientation selectivity in rat visual cortex.

In visual masking the perception of a target stimulus is impaired by a preceding (forward) or succeeding (backward) mask stimulus. The illusion is of interest because it allows uncoupling of the physical stimulus, its neuronal representation, and its perception. To understand the neuronal correlates of masking, we examined how masks affected the neuronal responses to oriented target stimuli in the primary visual cortex (V1) of anesthetized rats (n = 37). Target stimuli were circular gratings with 12 orientations; mask stimuli were plaids created as a binarized sum of all possible target orientations. Spatially, masks were presented either overlapping or surrounding the target. Temporally, targets and masks were presented for 33 ms, but the stimulus onset asynchrony (SOA) of their relative appearance was varied. For the first time, we examine how spatially overlapping and center-surround masking affect orientation discriminability (rather than visibility) in V1. Regardless of the spatial or temporal arrangement of stimuli, the greatest reductions in firing rate and orientation selectivity occurred for the shortest SOAs. Interestingly, analyses conducted separately for transient and sustained target response components showed that changes in orientation selectivity do not always coincide with changes in firing rate. Given the near-instantaneous reductions observed in orientation selectivity even when target and mask do not spatially overlap, we suggest that monotonic visual masking is explained by a combination of neural integration and lateral inhibition.

Orientation selectivity in rat primary visual cortex emerges earlier with low-contrast and high-luminance stimuli.

In natural vision, rapid and sustained variations in luminance and contrast change the reliability of information available about a visual scene, and markedly affect both neuronal and behavioural responses. The hallmark property of neurons in primary visual cortex (V1), orientation selectivity, is unaffected by changes in stimulus contrast, but it remains unclear how sustained differences in mean luminance and contrast affect the time-course of orientation selectivity, and the amount of information that neurons carry about orientation. We used reverse correlation with characterize the temporal dynamics of orientation selectivity in rat V1 neurons under four luminance-contrast conditions. We show that orientation selectivity and mutual information between neuronal responses and stimulus orientation are invariant to contrast or mean luminance. Critically, the time-course of the emergence of orientation selectivity was affected by both factors; response latencies were longer for low- than high-luminance gratings, and surprisingly, response latencies were also longer for high- than low-contrast gratings. Modelling suggests that luminance-modulated changes in feedforward gain, in combination with hyperpolarization caused by high contrasts can account for our physiological data. The hyperpolarization at high contrasts may increase signal-to-noise ratios, whereas a more depolarized membrane may lead to greater sensitivity to weak stimuli.

Are Synonymous Sites in Primates and Rodents Functionally Constrained?

It has been claimed that synonymous sites in mammals are under selective constraint. Furthermore, in many studies the selective constraint at such sites in primates was claimed to be more stringent than that in rodents. Given the larger effective population sizes in rodents than in primates, the theoretical expectation is that selection in rodents would be more effective than that in primates. To resolve this contradiction between expectations and observations, we used processed pseudogenes as a model for strict neutral evolution, and estimated selective constraint on synonymous sites using the rate of substitution at pseudosynonymous and pseudononsynonymous sites in pseudogenes as the neutral expectation. After controlling for the effects of GC content, our results were similar to those from previous studies, i.e., synonymous sites in primates exhibited evidence for higher selective constraint that those in rodents. Specifically, our results indicated that in primates up to 24% of synonymous sites could be under purifying selection, while in rodents synonymous sites evolved neutrally. To further control for shifts in GC content, we estimated selective constraint at fourfold degenerate sites using a maximum parsimony approach. This allowed us to estimate selective constraint using mutational patterns that cause a shift in GC content (GT ↔ TG, CT ↔ TC, GA ↔ AG, and CA ↔ AC) and ones that do not (AT ↔ TA and CG ↔ GC). Using this approach, we found that synonymous sites evolve neutrally in both primates and rodents. Apparent deviations from neutrality were caused by a higher rate of C → A and C → T mutations in pseudogenes. Such differences are most likely caused by the shift in GC content experienced by pseudogenes. We conclude that previous estimates according to which 20-40% of synonymous sites in primates were under selective constraint were most likely artifacts of the biased pattern of mutation.

Determinants of treatment-related paradoxical reactions during anti-tuberculosis therapy: a case control study.

BACKGROUND: Inflammatory response following initial improvement with anti-tuberculosis (TB) treatment has been termed a paradoxical reaction (PR). HIV co-infection is a recognised risk, yet little is known about other predictors of PR, although some biochemical markers have appeared predictive. We report our findings in an ethnically diverse population of HIV-infected and uninfected adults. METHODS: Prospective and retrospective clinical and laboratory data were collected on TB patients seen between January 1999-December 2008 at four UK centres selected to represent a wide ethnic and socio-economic mix of TB patients. Data on ethnicity and HIV status were obtained for all individuals. The associations between other potential risk factors and PR were assessed in a nested case-control study. All PR cases were matched two-to-one to controls by calendar time and centre. RESULTS: Of 1817 TB patients, 82 (4.5 %, 95 % CI 3.6-5.5 %) were identified as having a PR event. The frequency of PR was 14.4 % (18/125; 95 % CI 8.2-20.6 %) and 3.8 % (64/1692; 2.9-4.7) for HIV-positive and HIV-negative individuals respectively. There were no differences observed in PR frequency according to ethnicity, although the site was more likely to be pulmonary in those of black and white ethnicity, and lymph node disease in those of Asian ethnicity. In multivariate analysis of the case-control cohort, HIV-positive patients had five times the odds of developing PR (aOR = 5.05; 95 % CI 1.28-19.85, p = 0.028), whilst other immunosuppression e.g. diabetes, significantly reduced the odds of PR (aOR = 0.01; 0.00-0.27, p = 0.002). Patients with positive TB culture had higher odds of developing PR (aOR = 6.87; 1.31-36.04, p = 0.045) compared to those with a negative culture or those in whom no material was sent for culture. Peripheral lymph node disease increased the odds of a PR over 60-fold 4(9.60-431.25, p < 0.001). CONCLUSION: HIV was strongly associated with PR. The increased potential for PR in people with culture positive TB suggests that host mycobacterial burden might be relevant. The increased risk with TB lymphadenitis may in part arise from the visibility of clinical signs at this site. Non-HIV immunosuppression may have a protective effect. This study highlights the difficulties in predicting PR using routinely available demographic details, clinical symptoms or biochemical markers.

Mycotic Aneurysm following a Dog Bite: The Value of the Clinical History and Molecular Diagnostics.

A 63-year-old Caucasian taxi driver presented with a 3-week history of malaise, night sweats, 7 kg weight loss, generalized arthralgia, and persistent mid-lower abdominal pain. Blood inflammatory markers were raised, and a computed tomography scan demonstrated an irregular degeneration of the infrarenal aorta, with a differential diagnosis including aortic infection. An urgent type IV thoracoabdominal aneurysm repair was performed with a rifampicin-soaked aortic tube graft during an open procedure. No organisms were grown from multiple peripheral blood cultures or culture of the affected aorta. However, subsequent 16S ribosomal polymerase chain reaction analysis of the resected aorta identified Capnocytophaga canimorsus as the causative organism-a commensal that lives in the mouth of dogs and cats. The patient subsequently gave a history of multiple bites from his pet dog over recent months-the likely source of infection. He was treated with 8 weeks of intravenous antibiotics before switching to oral antibiotics for an additional 6 weeks.