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No clear evidence‐based treatment paradigm currently exists for refractory and super‐refractory status epilepticus, which can result in significant mortality and morbidity. While patients are typically treated with antiepileptic drugs and anesthetics, neurosurgical neuromodulation techniques can also be considered. We present a novel case in which responsive neurostimulation was used to effectively treat a patient who had developed super‐refractory status epilepticus, later consistent with epilepsia partialis continua, that was refractory to antiepileptic drugs, immunomodulatory therapies, and transcranial magnetic stimulation. This case demonstrates how regional therapy provided by responsive neurostimulation can be effective in treating super‐refractory status epilepticus through neuromodulation of seizure networks.

Consciousness is not explained by a single mechanism, rather it involves multiple specialized neural systems overlapping in space and time. We hypothesize that synergistic, large-scale subcortical and cortical attention and signal processing networks encode conscious experiences. To identify brain activity in conscious perception without overt report, we classified visual stimuli as perceived or not using eye measurements. Report-independent event-related potentials and functional magnetic resonance imaging (fMRI) signals both occurred at early times after stimuli. Direct recordings revealed a novel thalamic awareness potential linked to conscious visual perception based on report. fMRI showed thalamic and cortical detection, arousal, attentional salience, task-positive, and default mode networks were involved independent of overt report. These findings identify a specific sequence of neural mechanisms in human conscious visual perception.One-Sentence SummaryHuman conscious visual perception engages large-scale subcortical and cortical networks even without overt report.

Speaking precisely is important for effective verbal communication, and articulatory gain is one component of speech motor control that contributes to achieving this goal. Given that the basal ganglia have been proposed to regulate the speed and size of limb movement, that is, movement gain, we explored the basal ganglia contribution to articulatory gain, through local field potentials (LFP) recorded simultaneously from the subthalamic nucleus (STN), precentral gyrus, and postcentral gyrus. During STN deep brain stimulation implantation for Parkinson’s disease, participants read aloud consonant-vowel-consonant syllables. Articulatory gain was indirectly assessed using the F2 Ratio, an acoustic measurement of the second formant frequency of/i/vowels divided by/u/vowels. Mixed effects models demonstrated that the F2 Ratio correlated with alpha and theta activity in the precentral gyrus and STN. No correlations were observed for the postcentral gyrus. Functional connectivity analysis revealed that higher phase locking values for beta activity between the STN and precentral gyrus were correlated with lower F2 Ratios, suggesting that higher beta synchrony impairs articulatory precision. Effects were not related to disease severity. These data suggest that articulatory gain is encoded within the basal ganglia-cortical loop.

The importance of the basal ganglia in modulating cognitive and motor behaviors is well known, yet how the basal ganglia participate in the uniquely human behavior of speech is poorly understood. The subthalamic nucleus (STN) is well positioned to facilitate two basal ganglia functions critical for speech: motor learning and gain modulation. Using a novel paradigm to study cortical-subcortical interactions during speech in patients undergoing awake DBS surgery, we found evidence for a left opercular hyperdirect pathway in humans by stimulating in the STN and examining antidromic evoked activity in the left temporal, parietal and frontal opercular cortex. These high resolution cortical and subcortical mapping data provided evidence for hyperdirect connectivity between Broca’s area (typically corresponding to pars triangularis and pars opercularis of the inferior frontal gyrus) and the STN. In addition, we observed evoked potentials consistent with the presence of monosynaptic projections from areas of opercular speech cortex that are primarily sensory, including auditory cortex, to the STN. These connections may be unique to humans, evolving alongside the ability for speech.SIGNIFICANCEUsing intracranial recordings from the basal ganglia and cortex in subjects undergoing deep brain stimulation, this study provides evidence for monosynaptic cortical inputs from motor planning, motor sensory, and auditory sensory cortices to the subthalamic nucleus. These observations suggest that in humans, the cortical-basal ganglia hyperdirect pathway is uniquely positioned to participate in speech production. Moreover, the existence of a monosynaptic connection between human sensory cortical areas and the subthalamic nucleus indicates a need to update traditional models of information transfer within cortical-basal ganglia-thalamocortical circuitry, which has significant implications for understanding other human cognitive behavior or dysfunction.

To determine if simultaneous bilateral scalp EEG (scEEG) can accurately detect a contralateral seizure onset in patients with unilateral intracranial EEG (IEEG) implantation.We evaluated 39 seizures from 9 patients with bitemporal epilepsy who underwent simultaneous scEEG and IEEG (SSIEEG). To simulate conditions of unilateral IEEG implantation with a missed contralateral seizure onset, we analyzed the IEEG recording contralateral to the seizure onset (CL- IEEG), in conjunction with simultaneous scEEG. The following criteria were evaluated between scEEG and CL- IEEG (1) latency: the time to onset of EEG seizure (2) location: concordance of ictal onset zones and (3) pattern: congruence of EEG morphology and frequency.SSIEEG correctly lateralized 36/39 (92.3%) seizures compared to 13/39 (33.3%) seizures using CL- IEEG alone (OR = 24.0, p 0.01), 33 (84.6%) seizures using scEEG alone (OR = 2.2, p = 0.29) and 26 (66.9%) seizures using time of clinical onset alone (OR = 6.0, p = 0.01). For the three criteria evaluated, (1) 22/39 (56.4%) seizures had an earlier onset on the scEEG, compared to CL- IEEG; (2) lack of congruence of location of seizure onset was noted in 33/39 (84.6%) of the seizures; and (3) 22/39 (56.4%) seizures did not have a congruent ictal pattern.The chronological, topographic and morphologic features of SSIEEG can accurately detect the hemisphere of seizure onset in most cases with unilateral IEEG implantation. SSIEEG is significantly better than, IEEG, scEEG or clinical onset alone in this scenario. We propose that SSIEEG should be considered in all cases of intractable focal epilepsy undergoing unilateral IEEG evaluation.

There is great interest in identifying the neurophysiological underpinnings of speech production. Deep brain stimulation (DBS) surgery is unique in that it allows intracranial recordings from both cortical and subcortical regions in patients who are awake and speaking. The quality of these recordings, however, may be affected to various degrees by mechanical forces resulting from speech itself. Here we describe the presence of speech-induced artifacts in local-field potential (LFP) recordings obtained from mapping electrodes, DBS leads, and cortical electrodes. In addition to expected physiological increases in high gamma (60-200 Hz) activity during speech production, time-frequency analysis in many channels revealed a narrowband gamma component that exhibited a pattern similar to that observed in the speech audio spectrogram. This component was present to different degrees in multiple types of neural recordings. We show that this component tracks the fundamental frequency of the participant’s voice, correlates with the power spectrum of speech and has coherence with the produced speech audio. A vibration sensor attached to the stereotactic frame recorded speech-induced vibrations with the same pattern observed in the LFPs. No corresponding component was identified in any neural channel during the listening epoch of a syllable repetition task. These observations demonstrate how speech-induced vibrations can create artifacts in the primary frequency band of interest. Identifying and accounting for these artifacts is crucial for establishing the validity and reproducibility of speech-related data obtained from intracranial recordings during DBS surgery.

The mechanism of action of deep brain stimulation (DBS) for Parkinson’s disease remains unclear. Studies have shown that DBS decreases pathological beta hypersynchrony between the basal ganglia and motor cortex. However, little is known about DBS’s effects on long range corticocortical synchronization. Here, we use machine learning combined with spectral graph theory to compare resting-state cortical connectivity between the off and on-stimulation states and compare these differences to healthy controls. We found that turning DBS on increased high beta and gamma band coherence in a cortical circuit spanning the motor, occipitoparietal, middle temporal, and prefrontal cortices. We found no significant difference between DBS-off and controls in this network with multivariate pattern classification showing that the brain connectivity pattern in control subjects is more like those during DBS-off than DBS-on. These results show that therapeutic DBS increases spontaneous high beta-gamma synchrony in a network that couples motor areas to broader cognitive systems.

An enduring neuroscientific debate concerns the extent to which neural representation is restricted to networks of patches specialized for particular domains of perceptual input (Kaniwsher et al., 1997; Livingstone et al., 2019), or distributed outside of these patches to broad areas of cortex as well (Haxby et al., 2001; Op de Beeck, 2008). A critical level for this debate is the localization of the neural representation of the identity of individual images, (Spiridon & Kanwisher, 2002) such as individual-level face or written word recognition. To address this debate, intracranial recordings from 489 electrodes throughout ventral temporal cortex across 17 human subjects were used to assess the spatiotemporal dynamics of individual word and face processing within and outside cortical patches strongly selective for these categories of visual information. Individual faces and words were first represented primarily only in strongly selective patches and then represented in both strongly and weakly selective areas approximately 170 milliseconds later. Strongly and weakly selective areas contributed non-redundant information to the representation of individual images. These results can reconcile previous results endorsing disparate poles of the domain specificity debate by highlighting the temporally segregated contributions of different functionally defined cortical areas to individual level representations. Taken together, this work supports a dynamic model of neural representation characterized by successive domain-specific and distributed processing stages. SIGNIFICANCE STATEMENT The visual processing system performs dynamic computations to differentiate visually similar forms, such as identifying individual words and faces. Previous models have localized these computations to 1) circumscribed, specialized portions of the brain, or 2) more distributed aspects of the brain. The current work combines machine learning analyses with human intracranial recordings to determine the neurodynamics of individual face and word processing in and outside of brain regions selective for these visual categories. The results suggest that individuation involves computations that occur first in primarily highly selective parts of the visual processing system, then later recruits highly and non-highly selective regions. These results mediate between extant models of neural specialization by suggesting a dynamic domain specificity model of visual processing.

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their “intermediate” microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.

BACKGROUND: Despite the impact of Parkinson disease (PD) on speech communication, there is no consensus regarding the effect of lead location on voice-related outcomes in subthalamic nucleus (STN) deep brain stimulation (DBS). OBJECTIVE: To determine the relationship of stimulation location to changes in cepstral analyses of voice following STN DBS. METHODS: Speech pathology evaluations were obtained from 14 PD subjects, before and after STN DBS, including audio-perceptual voice ratings (overall severity, loudness, hoarseness changes), measured indices of dysphonia (cepstral peak prominence and cepstral spectral index of dysphonia), and phonatory aerodynamics. The contact locations used for active stimulation at the time of postoperative voice evaluations were determined and assessed in relation to voice outcomes. RESULTS: Voice outcomes remained relatively unchanged on average. Stimulation locations in the anterior portion of the sensorimotor region of the left STN, however, were associated with improvements in voice severity scores, cepstral spectral index of dysphonia, shortness of breath, and phonatory airflow during connected speech. Posterior locations were associated with worsening of these outcomes. Variation in the medial-lateral or dorsal-ventral position on the left, and in any direction on the right, did not correlate with any voice outcome. CONCLUSION: Active contact placement within the anterior sensorimotor STN was associated with improved perceptual and acoustic-aerodynamic voice-related outcomes. These findings suggest an STN topography for improving airflow for speech, in turn improving how PD patients’ voices sound.

Cortico-basal ganglia interactions continuously shape the way we move. Ideas about how this circuit works are based largely on models those consider only firing rate as the mechanism of information transfer. A distinct feature of neural activity accompanying movement, however, is increased motor cortical and basal ganglia gamma synchrony. To investigate the relationship between neuronal firing in the basal ganglia and cortical gamma activity during movement, we analysed human ECoG and subthalamic nucleus (STN) unit activity during hand gripping. We found that fast reaction times were preceded by enhanced STN spike-to-cortical gamma phase coupling, indicating a role in motor preparation. Importantly, increased gamma phase coupling occurred independent of changes in mean STN firing rates, and the relative timing of STN spikes was offset by half a gamma cycle for ipsilateral vs. contralateral movements, indicating that relative spike timing is as relevant as firing rate for understanding cortico-basal ganglia information transfer.

Background: A number of centers across the world offer short daily hemodialysis (SDHD) treatments. To date, cefazolin pharmacokinetics have not been described in patients undergoing SDHD. Objective: The purpose of this study was to investigate the effect of SDHD on the pharmacokinetics of cefazolin. Methods: This was a prospective, open-label, pharmacokinetic study of cefazolin during SDHD in 10 noninfected patients. Participants received a 1-g intravenous (IV) infusion of cefazolin after SDHD on study day 1 and a second dose after SDHD on study day 2. To determine the concentration of cefazolin, 6 blood samples were drawn at 0, 1, 2, 2.3, 4, and 24 hours after initiation of dialysis on day 2, and 2 dialysate samples were drawn at 1 and 2 hours after initiation of dialysis on day 2. Samples were analyzed using high-performance liquid chromatography, and pharmacokinetic parameters were determined. Results: Median interdialysis clearance was 0.16 L/h (interquartile range [IQR]: 0.11-0.21 L/h), and median intradialysis clearance was 1.95 L/h (IQR: 1.66-2.45 L/h). Median interdialysis half-life was 28.2 hours (IQR: 23.5-59.3 hours) as compared with a median intradialysis half-life of 2.3 hours (IQR: 1.7-2.7 hours). The median percentage removal of cefazolin during dialysis was 41% (IQR: 35%-53%). Conclusion and Relevance: Estimated cefazolin dialysis clearance is similar to previous estimates with conventional thrice-weekly regimens. Current dosing recommendations of 1 g IV post-SDHD achieve total serum drug concentrations greater than 40 mg/L in all patients, which is the total drug concentration required for bactericidal activity against Staphylococcus species.

PAMAM dendrimers have been conjectured for a wide range of biomedical applications due to their tuneable physicochemical properties. However, their application has been hindered by uncertainties in their cytotoxicity, which is influenced by dendrimer generation (i.e. size and surface group density), surface chemistry, and dosage, as well as cell specificity. In this review, biomedical applications of polyamidoamine (PAMAM) dendrimers and some related cytotoxicity studies are first outlined. Alongside these in vitro experiments, lipid membranes such as supported lipid bilayers (SLBs), liposomes, and Langmuir monolayers have been used as cell membrane models to study PAMAM dendrimer-membrane interactions. Related experimental and theoretical studies are summarized, and the physical insights from these studies are discussed to shed light on the fundamental understanding of PAMAM dendrimer-cell membrane interactions. We conclude with a summary of some questions that call for further investigations.

Epilepsy is a chronic brain disorder, and for at least one- third of epilepsy patients, medications do not adequately control seizures and surgery is the only potential cure. An automated seizure detector that requires a short period of normal EEG would shorten the seizure monitoring durations, decrease the need for manual assessment of large amount of recorded EEG data, and accordingly assist the neurologists focus on improving quality of care. In this work, we propose a novel approach based on the extended cumulative sum test to detect seizures using intracranial EEG. Different than the existing machine learning approaches, this method requires only a short period of normal EEG for training. In addition to a new proposed feature based on partial directed coherence and random graph theory, in this work, previously developed features used to characterize seizures are used as features in cumulative sum test for seizure detection. A total of 33 intracranial EEG recordings collected from a total of 9 patients corresponding to three different datasets have been used for the analysis purposes: (i) the first dataset includes 11 recorded EEG files (~12.5 min) from 4 patients; (ii) the second dataset includes 20 recorded EEG files (~30 min) from 4 patients; and (iii) two 24-hour long EEG files from a single patient. The proposed detector achieved a mean sensitivity and mean specificity for the first (0.77, 0.86), second (0.88, 0.9) and third datasets (0.92, 0.94) respectively. Statistical detection of seizures has shown success in detecting seizures without the need for highly customizable parameters or previously labelled EEG data. The proposed method could be used in real-time at hospital settings with a minimum requirement of training data.

Many language functions are traditionally assigned to cortical brain areas, leaving the contributions of subcortical structures to language processing largely unspecified. The present study examines a potential role of the subthalamic nucleus (STN) in lexical processing, specifically, reading aloud of words (e.g., 'fate') and pseudowords (e.g., 'fape'). We recorded local field potentials simultaneously from the STN and the cortex (precentral, postcentral, and superior temporal gyri) of 13 people with Parkinson's disease undergoing awake deep brain stimulation and compared STN's lexicality-related neural activity with that of the cortex. Both STN and cortical activity demonstrated significant task-related modulations, but the lexicality effects were different in the two brain structures. In the STN, an increase in gamma band activity (31-70 Hz) was present in pseudoword trials compared to word trials during subjects' spoken response. In the cortex, a greater decrease in beta band activity (12-30 Hz) was observed for pseudowords in the precentral gyrus. Additionally, 11 individual cortical sites showed lexicality effects with varying temporal and topographic characteristics in the alpha and beta frequency bands. These findings suggest that the STN and the sampled cortical regions are involved differently in the processing of lexical distinctions.

Current knowledge of the functional anatomy of the subthalamic nucleus and globus pallidus, discovered through microelectrode recording and postoperative imaging, justifies purely anatomic targeting for deep brain stimulation (DBS). Interventional MRI (iMRI)-DBS is more anatomically accurate than traditional awake procedures and has similar clinical outcomes without increased risk or increased operative times. iMRI lead implantation allows patients to receive DBS therapy who cannot tolerate or do not agree to undergo an awake procedure. This article describes considerations for iMRI-DBS implantation in the subthalamic nucleus and globus pallidus, including patient selection, technique of electrode placement, expected outcomes, and potential complications.

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also demonstrate, for the first time in humans, a mechanism through which the premotor and sensory cortices are functionally connected to the STN.

The sensorimotor cortex is somatotopically organized to represent the vocal tract articulators such as lips, tongue, larynx, and jaw. How speech and articulatory features are encoded at the subcortical level, however, remains largely unknown. We analyzed LFP recordings from the subthalamic nucleus (STN) and simultaneous electrocorticography recordings from the sensorimotor cortex of 11 human subjects (1 female) with Parkinson´s disease during implantation of deep-brain stimulation (DBS) electrodes while they read aloud three-phoneme words. The initial phonemes involved either articulation primarily with the tongue (coronal consonants) or the lips (labial consonants). We observed significant increases in high-gamma (60?150 Hz) power in both the STN and the sensorimotor cortex that began before speech onset and persisted for the duration of speech articulation. As expected from previous reports, in the sensorimotor cortex, the primary articulators involved in the production of the initial consonants were topographically represented by high-gamma activity. We found that STN high-gamma activity also demonstrated specificity for the primary articulator, although no clear topography was observed. In general, subthalamic high-gamma activity varied along the ventral?dorsal trajectory of the electrodes, with greater high-gamma power recorded in the dorsal locations of the STN. Interestingly, the majority of significant articulator-discriminative activity in the STN occurred before that in sensorimotor cortex. These results demonstrate that articulator-specific speech information is contained within high-gamma activity of the STN, but with different spatial and temporal organization compared with similar information encoded in the sensorimotor cortex. Fil: Chrabaszcz, Anna. University of Pittsburgh; Estados Unidos Fil: Neumann, Wolf Julian. Universität zu Berlin; Alemania Fil: Stretcu, Otilia. University of Pittsburgh; Estados Unidos Fil: Lipski, Witold J.. University of Pittsburgh; Estados Unidos Fil: Dastolfo Hromack, Christina A.. University of Pittsburgh; Estados Unidos Fil: Bush, Alan. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina Fil: Wang, Dengyu. Tsinghua University; China. University of Pittsburgh; Estados Unidos Fil: Crammond, Donald J.. University of Pittsburgh; Estados Unidos Fil: Shaiman, Susan. University of Pittsburgh; Estados Unidos Fil: Dickey, Michael W.. University of Pittsburgh; Estados Unidos Fil: Holt, Lori L.. University of Pittsburgh; Estados Unidos Fil: Turner, Robert S.. University of Pittsburgh; Estados Unidos Fil: Fiez, Julie A.. University of Pittsburgh; Estados Unidos Fil: Richardson, R. Mark. University of Pittsburgh; Estados Unidos

Recent electrocorticography data have demonstrated excessive coupling of beta-phase to gamma-amplitude in primary motor cortex and that deep brain stimulation facilitates motor improvement by decreasing baseline phase-amplitude coupling. However, both the dynamic modulation of phase-amplitude coupling during movement and the general cortical neurophysiology of other movement disorders, such as essential tremor, are relatively unexplored. To clarify the relationship of these interactions in cortical oscillatory activity to movement and disease state, we recorded local field potentials from hand sensorimotor cortex using subdural electrocorticography during a visually cued, incentivized handgrip task in subjects with Parkinson’s disease ( n = 11), with essential tremor ( n = 9) and without a movement disorder ( n = 6). We demonstrate that abnormal coupling of the phase of low frequency oscillations to the amplitude of gamma oscillations is not specific to Parkinson’s disease, but also occurs in essential tremor, most prominently for the coupling of alpha to gamma oscillations. Movement kinematics were not significantly different between these groups, allowing us to show for the first time that robust alpha and beta desynchronization is a shared feature of sensorimotor cortical activity in Parkinson’s disease and essential tremor, with the greatest high-beta desynchronization occurring in Parkinson’s disease and the greatest alpha desynchronization occurring in essential tremor. We also show that the spatial extent of cortical phase-amplitude decoupling during movement is much greater in subjects with Parkinson’s disease and essential tremor than in subjects without a movement disorder. These findings suggest that subjects with Parkinson’s disease and essential tremor can produce movements that are kinematically similar to those of subjects without a movement disorder by reducing excess sensorimotor cortical phase-amplitude coupling that is characteristic of these diseases. * Abbreviations : DBS : deep brain stimulation ECoG : electrocorticography

Why does closed-loop invasive brain stimulation improve seizure control in some patients with epilepsy, but not others? The RNS System, the only FDA-approved bi-directional brain-computer interface, has been shown to improve seizure control in patients with refractory epilepsy, although the mechanisms behind this success are undefined. We analyzed recordings from the RNS System and discovered two main categories of electrophysiological signatures of stimulation-induced modulation of the seizure network. Direct effects included ictal inhibition and early frequency modulation but did not correlate with improved clinical outcomes. Only indirect effects, those occurring remote from triggered stimulation, predicted improved clinical outcomes. These indirect effects, which included spontaneous ictal inhibition, frequency modulation, fragmentation, and ictal duration modulation, may reflect progressive local epileptogenic network compartmentalization that hinders the spread of pathological synchrony from recruiting neuronal populations. Our findings suggest that responsiveness to RNS may be explained by chronic stimulation-induced modulation of seizure network activity, rather than direct effects on each detected seizure.

We describe the case of a 30-year-old man with HIV with an elevated creatinine and three litres per day of urine output. Using this patient as a framework, we review a diagnostic approach to acute kidney injury with polyuria. This case emphasizes the importance of a complete diagnostic evaluation of acute kidney injury. Without this approach, it would have been easy to attribute the patient’s acute kidney injury to his HIV and necrotizing peri-anal infection, instead of the true life- threatening cause.

SUMMARY Background Patients on haemodialysis have been identified as high-risk for medication discrepancies and adverse drug events. Medication reconciliation is an important patient safety initiative to prevent adverse drug events. The primary objective of our study was to determine the number and types of medication discrepancies and drug therapy problems (DTPs) identified in patients on haemodialysis. Our second objective was to assess the potential clinical impact and severity of all unintentional medication discrepancies identified. Methods Patients in an academic haemodialysis unit were interviewed to obtain a best possible medication history (BPMH) between May and August 2010. The BPMH was documented and discrepancies were identified, classified and resolved with the interprofessional team. An interprofessional panel conducted a discrepancy clinical impact assessment for potential adverse drug events. Results Two hundred and twenty-eight patients on haemodialysis were interviewed and 512 discrepancies were identified for 151 patients (3.4 discrepancies per patient). Of these, 174 (34%) were undocumented intentional discrepancies and 338 (66%) were unintentional discrepancies. The unintentional discrepancies were classified as 21% omissions, 36% commissions and 43% incorrect dose/frequency. Most drug therapy problems were related to patient taking a medication that was not indicated (25%), medication required but patient not taking (25%), patient not willing to take the medication as prescribed (28%) or incorrect dosing of a drug (20%). Overall, 6% of discrepancies were classified as clinically significant potential adverse drug events. Conclusion Medication discrepancies appear to be common in patients on haemodialysis. Formal interprofessional medication reconciliation practice models are essential to identify discrepancies and prevent patients from experiencing adverse drug events.

Warfarin is frequently used in the hemodialysis (HD) population for atrial fibrillation (AF) and venous thromboembolism (VTE); however, there is insufficient evidence to support this practice. Given that HD patients have 3 - 10 times the risk for both stroke and bleeding than the general population, anticoagulation in these patients is controversial. Time in therapeutic range (TTR) is accepted as a surrogate outcome of clinical effectiveness and safety of warfarin. The primary objective of this study was to evaluate TTR in an HD population. A 6-year retrospective chart review was performed in 46 HD patients on warfarin (target international normaized ratio (INR)=2-3). One year of patient data was collected, which included weekly INRs, demographics and clinical outcomes. TTR was calculated using the Rosendaal and fraction of INRs in range methods. The mean TTR using the Rosendaal and fraction of INRs in range method was 49.2±14.6% and 44.2±13.5%, respectively. Patients were 3 times more likely to be below target than above it, suggesting they were more often at risk of inadequate efficacy rather than toxicity. There were 9 serious bleeding and 9 thrombotic events; these occurred in patients with a TTR

Background: National guidelines recommend using anemia management protocols to guide treatment. The objective of this study was to determine if an anemia management protocol would improve hemoglobin (Hgb) indices in hemodialysis patients and to measure whether the protocol would reduce the use and cost of darbepoetin alfa (DBO) and intravenous (IV) iron in hemodialysis patients. Methods: An anemia management protocol was created and implemented for hemodialysis patients at our institution. A retrospective observational review of the use of DBO and IV iron as well as changes in Hgb, transferrin saturation and ferritin in 174 patients was conducted 6 months before and after implementation of the anemia protocol. Results: The number of Hgb measurements in the target range increased from 44.3 to 46.0% (p = 0.48) after protocol implementation. The mean weekly dose of DBO was reduced from 34.56 ± 31.12 to 31.11 ± 28.64 μg post-protocol implementation (p = 0.011), which translated to a cost savings of USD 41,649 over 6 months. The mean monthly IV iron dose also decreased from 139.56 ± 98.83 to 97.65 ± 79.05 mg (p < 0.005), a cost savings of USD 18,594 over the same time period. Conclusion: The use of an anemia management protocol resulted in the deprescribing of DBO and iron agents while increasing the number of patients in the target Hgb range, which led to significant cost savings in the treatment of anemia.

The lack of multivariate methods for decoding the representational content of interregional neural communication has left it difficult to know what information is represented in distributed brain circuit interactions. Here we present Multi-Connection Pattern Analysis (MCPA), which works by learning mappings between the activity patterns of the populations as a factor of the information being processed. These maps are used to predict the activity from one neural population based on the activity from the other population. Successful MCPA-based decoding indicates the involvement of distributed computational processing and provides a framework for probing the representational structure of the interaction. Simulations demonstrate the efficacy of MCPA in realistic circumstances. Applying MCPA to fMRI data shows that interactions between visual cortex regions are sensitive to information that distinguishes individual natural images, suggesting that image individuation occurs through interactive computation across the visual processing network. MCPA-based representational similarity analyses (RSA) results support models of error coding in interactions among regions of the network. Further RSA analyses relate the non-linear information transformation operations between layers of a computational model (HMAX) of visual processing to the information transformation between regions of the visual processing network. Additionally, applying MCPA to human intracranial electrophysiological data demonstrates that the interaction between occipital face area and fusiform face area contains information about individual faces. Thus, MCPA can be used to assess the information represented in the coupled activity of interacting neural circuits and probe the underlying principles of information transformation between regions.

We undertook this study to characterize the epidemiology of acute kidney injury (AKI) in Canadian critical care units. We aimed to identify predictors of mortality for patients diagnosed with AKI.We conducted a prospective cohort study of consecutive patients admitted to critical care units at five Canadian hospitals over a 30-day period. Each patient was followed until hospital discharge or for a maximum of 30 days. The serum creatinine criteria for the Acute Kidney Injury Network (AKIN-SCr) system were used to identify, classify, and characterize patients who developed AKI. We used multivariable logistic regression to predict 30-day mortality among patients with AKI.We identified 603 patients, 161 (26.7%) of whom developed AKI. Compared to patients without AKI, those with AKI were more likely to die (29.2% vs 8.6%, P0.001). The risk of death increased with increasing AKIN-SCr stage (P0.001). In all, 19 patients (11.8% of those with AKI) commenced dialysis a median of one day (interquartile range, one to two days) after AKI diagnosis. At AKI diagnosis, the blood urea nitrogen (BUN) level (adjusted odds ratio [OR] 1.68, 95% confidence interval [CI] 1.01 to 2.79/10 mmol·L(-1)) and serum bicarbonate (adjusted OR 0.88, 95% CI 0.81 to 0.95/1 mmol·L(-1)) were associated with 30-day mortality and predicted death with an area under the receiver-operating characteristic curve of 0.79 (95% CI 0.71 to 0.86).Acute kidney injury is a common complication of critical illness in Canada. The development of even the mildest stage of AKI is associated with a substantially higher risk of death. At AKI diagnosis, routine clinical data may be helpful for predicting adverse outcomes.

Tuberculosis is an important issue for nephrologists caring for dialysis patients. Because dialysis patients are immunocompromised, they are at higher risk for reactivation of latent tuberculosis, and they frequently have atypical presentation. Furthermore, hemodialysis units may foster rapid spread of active pulmonary tuberculosis. The diagnosis of active pulmonary tuberculosis still depends on detection of organisms by smear and culture. Newer nucleic acid detection techniques are more sensitive and specific. Nephrologists should remember that nonspecific presentation of tuberculosis including fever, weight loss, and adenopathy are more common in dialysis patients than in the general population, and diagnosis may require biopsy of extrapulmonary tissue. Detection of latent tuberculosis in dialysis patients should only be undertaken if treatment is planned. Generally, this should apply only to potential transplant candidates and younger dialysis patients with longer life expectancy. Tuberculin skin test is very insensitive in dialysis patients, and false-positives occur in patients born in countries where Bacillus Calmette-Guerin vaccine has been used. Blood tests using stimulation of gamma interferon have been shown to be more sensitive tests of latent tuberculosis and may be used in conjunction with tuberculin skin tests.

BACKGROUND Uncontrolled hy-per-parathyroidism causes bone marrow fibrosis, leading to erythropoietin (EPO) resistance. Medical treatment with cinacalcet is effective in reducing plasma parathyroid hormone (PTH) levels, but its effect on darbepoetin dosing is unknown. METHODS AND AIMS We conducted a retrospective cohort study of 40 end-stage renal disease (ESRD) patients (age: 55 ± 14; mean ± SD; 21:male) who had at least 12 months of cinacalcet therapy. The distribution of renal replacement therapies were: 14 peritoneal dialysis, 18 conventional hemodialysis and 8 nocturnal hemodialysis. Standard dialysis related biochemical indices and medications used were recorded. The primary objective of the study was to ascertain the difference in darbepoetin responsiveness before and after 12 months of cinacalcet therapy. Our secondary objective was to determine if there was a relationship between the changes in PTH and darbepoetin requirement. RESULTS Overall, PTH levels decreased from 197.5 (151.8; 249.2) to 66.1 (41.2; 136.5) (median (25th;75th percentile)) pmol/l; p < 0.001. Cinacalcet dose increased from 30.0 ± 6 to 63 ± 25 mg/day, p < 0.05. Hemoglobin remained unchanged (116 ± 13 to 116 ± 13 g/l), while darbepoetin requirement decreased from 40 (20; 60) to 24 (19; 59) μg/week, p = 0.02. The remainder of the dialysis-related biochemistry (electrolytes, calcium, phosphate, iron status) and vitamin D use remained unchanged. A reduction in PTH level of greater than 30% was experienced by 82.5% (33/40) of our cohort. Among the responders, the fall in PTH and reduction darbepoetin requirement were related (R = -0.48, p = 0.004). CONCLUSIONS Reduction of PTH by cinacalcet is associated with a decrease in darbepoetin requirement. The interface between bone and bone marrow in uremia represents a critical step in red blood cell production which merits further investigation.

Background: Since Mehta et al. reported the first successful use of regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) in 1990, RCA is increasingly used for CRRT because it provides filter patency with minimal risk of bleeding. However, RCA has been associated with significant metabolic complications including hypocalcemia, hypernatremia, metabolic alkalosis, and citrate toxicity. Objective: To describe our experience with a newly implemented RCA protocol with acid citrate dextrose formula A (ACD-A) and intravenous calcium gluconate, for use with PrismaFlex CRRT in critically ill patients with acute kidney injury. Methods: A retrospective chart review was conducted from May 1, 2006, until May 1, 2007, in a 16-bed medical-surgical university-affiliated intensive care unit. Data collected included dialysis filter life, patient and circuit metabolic parameters, and units of packed red blood cells transfused. Results: Forty-eight patients received dialysis with citrate (n = 178 fitters). Circuit clotting occurred in 24% of all filters. Mean ± SD filter life was 38.4 ± 25.9 hours, and filter survival at 48 hours was 38.2%. Persistent metabolic alkalosis while on CRRT was identified in 6 of 45 (13.3%) patients. Mild hypocalcemia (ionized calcium Conclusions: We found that anticoagulation of PrismaFlex CRRT with ACD-A and intravenous calcium gluconate provided reasonable filter patency, but with minor metabolic complications. Close monitoring of electrolyte and acid–base balance is required to minimize metabolic derangements.

Acute kidney injury (AKI) is an increasingly common problem among hospitalized patients. Patients who survive an AKI-associated hospitalization are at higher risk of de novo and worsening chronic kidney disease, end-stage kidney disease, cardiovascular disease, and death. For hospitalized patients with dialysis-requiring AKI, outpatient follow-up with a nephrologist within 90 days of hospital discharge has been associated with enhanced survival. However, most patients who survive an AKI episode do not receive any follow-up nephrology care. This narrative review describes the experience of two new clinical programs to care for AKI patients after hospital discharge: the Acute Kidney Injury Follow-up Clinic for adults (St. Michael's Hospital and University Health Network, Toronto, Canada) and the AKI Survivor Clinic for children (Cincinnati Children's Hospital, USA).MEDLINE, PubMed, ISI Web of Science.These two ambulatory clinics have been in existence for close to two (adult) and four (pediatric) years, and were developed separately and independently in different populations and health systems. The components of both clinics are described, including the target population, referral process, medical interventions, patient education activities, and follow-up schedule. Common elements include targeting patients with KDIGO stage 2 or 3 AKI, regular audits of the inpatient nephrology census to track eligible patients, medication reconciliation, and education on the long-term consequences of AKI.Despite the theoretical benefits of post-AKI follow-up and the clinic components described, there is no high quality evidence to prove that the interventions implemented in these clinics will reduce morbidity or mortality. Therefore, we also present a plan to evaluate the adult AKI Follow-up Clinic in order to determine if it can improve clinical outcomes compared to patients with AKI who do not receive follow-up care.Follow-up of AKI survivors is low, and this review describes two different clinics that care for patients who survive an AKI episode. We believe that sharing the experiences of the AKI Follow-up Clinic and AKI Survivor Clinic provide physicians with a feasible framework to implement their own clinics, which may help AKI patients receive outpatient care commensurate with their high risk status.L’insuffisance rénale aiguë (IRA) est un problème de plus en plus fréquent chez les patients hospitalisés. Ceux d’entre eux qui survivent à un épisode d’IRA courent un risque élevé de développer une insuffisance rénale chronique et des maladies cardiovasculaires ou d’aggraver leur état vers l’insuffisance rénale terminale et donc, la mort. Chez les patients hospitalisés pour insuffisance rénale aiguë nécessitant une hémodialyse, un taux de survie accru a été associé à un suivi par un néphrologue dans les 90 jours suivant la sortie de l’hôpital. Cependant, la majorité de ces patients ne bénéficient d’aucun suivi en néphrologie post-hospitalisation. La présente revue narrative s’attarde à décrire l’expérience de deux nouveaux programmes cliniques qui prennent en charge les patients après leur sortie de l’hôpital à la suite d’un épisode d’IRA. Il s’agit des programmes de l’« Acute Kidney Injury Follow-up Clinic » des hôpitaux St. Micheal et UHN de Toronto, et de la clinique pédiatrique « AKI Survivor Clinic for children » de l’hôpital pour enfants de Cincinnati, aux États-Unis.MEDLINE, PubMed, ISI le web des sciences.Ces cliniques ambulatoires, qui existent depuis près de deux ans (clinique pour adultes) et de quatre ans (clinique pédiatrique) se sont développées séparément et de façon indépendante pour des populations différentes, dans des systèmes de santé différents. Les constituants de ces deux cliniques se distinguent par l’identification de la population ciblée, le processus de présentation, les interventions médicales, les activités de sensibilisation auprès des patients et leur calendrier de suivi. Les parties communes incluent le recrutement de patients atteints d’IRA de stades 2 et 3 quant aux chances de l’amélioration globale de leurs résultats (KDIGO). Ce recrutement se fait par le passage en revue à intervalles réguliers des listes de patients hospitalisés aux unités néphrologiques afin d’identifier ceux qui sont admissibles au suivi. Ces parties communes incluent aussi un bilan comparatif des médicaments et la transmission d’informations sur les conséquences à long terme de l’insuffisance rénale aiguë.Malgré les bienfaits escomptés d’un suivi post-IRA et, les éléments cliniques décrits plus haut, il n’existe aucune preuve concrète que les procédures mises en œuvre dans ces programmes réduiront la morbidité ou la mortalité associées à la maladie. Par conséquent, nous présentons également un plan d’évaluation de la clinique pour adultes en suivi post-IRA afin de déterminer si son programme peut améliorer les résultats cliniques de ses patients en comparaison avec les patients ne recevant pas ce suivi.De façon générale, peu de patients ayant survécu à un épisode d’IRA reçoivent un suivi adéquat post-hospitalisation. Cette revue présente deux cliniques offrant ce suivi. Nous pensons que le partage de leurs expériences respectives peut poser un cadre réalisable aux médecins traitants qui souhaiteraient mettre sur pied leurs propres cliniques, afin d’offrir à leurs patients un suivi en externe répondant adéquatement à leur état de santé précaire.

Background: Acute kidney injury (AKI) complicates 15-20% of hospitalizations, and AKI survivors are at increased risk of chronic kidney disease and death. However, less than 20% of patients see a nephrologist within 3 months of discharge, even though a nephrologist visit within 90 days of discharge is associated with enhanced survival. To address this, we established an AKI Follow-Up Clinic and characterized the patterns of care delivered. Methods: We conducted a prospective time series study. All hospitalized patients who developed Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or 3 AKI were eligible. The pre-intervention period consisted of electronic reminders to the nephrology consults and cardiovascular surgery services to refer to the AKI Follow-Up Clinic. In the post-intervention period, eligible patients were automatically scheduled into the AKI Follow-Up Clinic at discharge. The primary outcome was the percentage of KDIGO stages 2-3 AKI survivors assessed by a nephrologist within 30 days of discharge. Results: In the pre-intervention period, 8 of 46 patients (17%) were seen by a nephrologist within 30 days after discharge, and no additional patients were seen for 90 days. In the post-intervention period, 17 of 69 patients (25%) were seen by a nephrologist within 30 days after discharge (p = 0.36), with an additional 30 patients seen in 90 days (47 of 69, 68%, p < 0.001). The mean serum creatinine was 99 (SD 35) µmol/l prior to hospitalization and 133 (58) µmol/l at 3 months. Fifty-five of 79 patients (70%) received at least 1 medical intervention at their first AKI Follow-Up Clinic visit. Conclusions: An AKI Follow-Up Clinic with an automatic referral process increased the proportion of patients seen at 90 days, but not 30 days post discharge. Being seen in the AKI Follow-Up Clinic was associated with interventions in most patients. Future research is needed to evaluate the effect of the AKI Follow-Up Clinic on patient-centered outcomes, but physicians should be aware that AKI survivors may benefit from close outpatient follow-up and a multipronged approach to care similarly for other high-risk populations.

In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.

End-stage renal disease (ESRD) is associated with a markedly increased cardiac calcification burden, as reflected by computed tomography scans of the heart. Nocturnal haemodialysis (NHD) is a novel form of renal replacement therapy which has multiple physiologic effects that may affect vascular calcification, including improvements in phosphate and uraemia control. The objective of the present study is the determination of the natural history of coronary calcification progression in patients converted to NHD, and the examination of the relationships between calcification risk factors and calcification progression in these patients.Thirty-eight ESRD patients were converted to NHD, and included in our observational cohort study. Coronary artery calcification scores (CACS) were documented at baseline and post-conversion (mean interscan duration 16+/-1 months). Other variables of interest included age, dialysis vintage, Framingham risk profile, phosphate binder and vitamin D usage, and plasma levels of calcium, phosphate and parathyroid hormone.Our cohort was stratified according to baseline calcification burden (minimal calcification: CACSor = 10 vs significant calcification: CACS10). Twenty-four patients had baseline CACSor = 10. These patients demonstrated no change in coronary calcification after 1 year of NHD (from 0.7+/-0.5 to 6+/-3, P = 0.1). Fourteen patients had higher initial CACS at baseline (1874+/-696), and demonstrated a non-significant 9% increase over 1 year to 2038+/-740 (P = 0.1). Plasma phosphate and calcium x phosphate product were significantly reduced, as were calcium-based phosphate binder and antihypertensive usage.Our study is the first to document CACS progression in a cohort of NHD patients. Further analysis of the effect of NHD on the physiology of cardiovascular calcification is required.

Background Hyperphosphatemia is an independent risk factor for mortality in hemodialysis (HD) patients. The relative importance of HD frequency and duration for phosphate removal is not clear. Short daily hemodialysis (SDHD) is a form of HD which offers increased treatment frequency. SDHD studies have not been shown to normalize serum phosphate. Methods Twenty-one patients were converted from conventional thrice weekly HD (CHD, 4 h/session) to SDHD (2 - 3.75 h/session, 5 - 6 sessions per week). The primary endpoint was the change in predialysis serum phosphate levels after conversion from CHD to SDHD. Changes in serum calcium levels, phosphate binder and vitamin D analogue usage, and serum parathyroid hormone (PTH) levels were measured as secondary endpoints. Results Mean duration of SDHD was 17.7 +/- 1.9 months. Mean treatment time was 2.63 +/- 0.10 h, and mean frequency was 5.3 +/- 0.1 sessions per week. Predialysis serum phosphate decreased from 1.99 +/- 0.12 mM at three months pre conversion to 1.27 +/- 0.10 mM at six months post conversion to SDHD (p = 0.002). Serum phosphate remained stable between six and 12 months post conversion (1.27 +/- 0.10 mM to 1.38 +/- 0.14 mM, p = 0.8). When patients were grouped according to SDHD sessional frequency (five sessions/week versus six sessions/week) and compared, no significant differences were found in predialysis serum phosphate levels at six or 12 months post conversion. There were no changes in serum calcium. Overall phosphate binder usage did not change pre and post conversion to SDHD. Serum PTH tended to decrease after one year of SDHD (44.2 +/- 13.4 pM to 21.4 +/- 5.9 pM, p = 0.07). Conclusion Conversion to SDHD significantly decreased serum phosphate. There may be a minimum hemodialysis duration below which increases in frequency are not able to compensate to achieve normal phosphate levels. Future studies are necessary to better characterize the relationship between HD duration and frequency with respect to phosphate removal.

AIM Anemia is adversely associated with poor uremia control and is an established cardiovascular risk factor in patients with end-stage renal disease (ESRD). Nocturnal home hemodialysis (NHD) is a novel form of renal replacement therapy that offers superior clearance of uremic solutes and improvements in several cardiovascular outcome parameters. We conducted a retrospective cohort study to test the hypotheses that augmenting the dose and frequency of dialysis by NHD would improve hemoglobin (Hb) concentrations and decrease requirement of erythropoietin (EPO) in ESRD patients. METHODS In 63 patients (mean age: 46 +/- 2 years) receiving NHD (mean duration: 2.1 +/- 0.2 years), Hb, EPO dose, iron saturation, ferritin were determined before and at six monthly repeated intervals after conversion to NHD. For comparison, 32 ESRD patients (mean age: 57 +/- 3 years) who remained on self-care conventional hemodialysis (CHD) were also studied. RESULTS There were no differences in baseline Hb concentrations, iron saturation, ferritin, or EPO dose between the two cohorts. After transfer from CHD to NHD, there were significant improvements in Hb concentrations (from 115 +/- 2 to 122 +/- 3 (6 months) and 124 +/- 2 (12 months) g/l, p = 0.03) despite a fall in EPO requirement (from 10,400 +/- 1400 to 8500 +/- 1300 (6 months) and 7600 +/- 1100 (12 months) U/week, p = 0.03). In contrast, CHD cohort had no change in EPO requirement (from 8300 +/- 1100 to 8100 +/- 1300 (6 months) and 8600 +/- 1000 (12 months) U/week, p > 0.05) or Hb concentrations (from 110 +/- 2 to 115 +/- 3 (6 months) and 115 +/- 2 (12 months), p > 0.05). There was a higher percentage of ESRD patients who did not require EPO in the NHD cohort (24% vs. 9.4%, p = 0.01). Lower Hb concentrations were noted in the CHD cohort despite higher iron saturation (0.25 +/- 0.01 (NHD) vs. 0.33 +/- 0.02 (CHD), p = 0.02) at the end of follow-up. CONCLUSIONS Enhancing uremic clearance by NHD resulted in a rise in Hb and a fall in EPO requirement.

Summary Background Topical bovine thrombin (TBT) is used as a topical haemostatic agent in haemodialysis (HD) units and for surgical procedures. It has caused allergic reactions during surgical procedures, but no previous cases have been reported with dialysis usage. Objective A case is reported of anaphylaxis due to TBT in an HD patient. This led to a determination of whether HD patients exposed to TBT develop specific IgE and IgG antibodies to TBT and an assessment of the frequency of allergic symptoms in HD patients as compared with peritoneal dialysis (PD) patients. Methods A cross-sectional study of 100 HD and 52 PD patients was performed using a questionnaire to determine allergic symptoms. An ELISA assay was developed to determine TBT-specific IgE and IgG serum antibodies among HD patients. HD patients without TBT exposure and age- and gender-matched blood donors served as controls. Results Allergic symptoms temporally related to dialysis reported by a questionnaire were significantly more frequent for HD patients than for PD patients: rhinoconjuctivitis 11% vs. 2%, asthma symptoms 20% vs. 6%, urticaria 23% vs. 8% (P values

Background. Thrombosis is the primary cause of access failure in polytetrafluoroethylene grafts and arteriovenous fistulas. It can lead to significant patient and access morbidity and mortality, and is difficult to prevent medically. Intervention is largely limited to maximizing access patency by detecting culprit lesions early and intervening with angioplasty or surgical revision. The most efficacious monitoring strategy is undetermined. Methods. This 3 year prospective study took advantage of a change in monitoring strategy used in a large dialysis centre to compare the efficacy of two methods used to monitor grafts and fistulas in order to prevent access thrombosis. Accesses were monitored using Duplex ultrasonography in year 1, while the saline ultrasound dilution technique (Transonic) became the primary monitoring strategy in year 3 (year 2 was a transition year). Risk factors for thrombosis were determined using multivariate survival analysis, and the performance of Duplex ultrasonography and Transonic monitoring was assessed. Results. A total of 303 656 access days at risk were assessed, with 344, 385 and 425 accesses in years 1, 2 and 3, respectively. The total thrombosis rate was 1.01/1000 access days in year 1 compared with 0.66/1000 access days in year 3. This was accomplished despite a reduction in procedure rates of 55% for angiograms, 13% for angioplasties and 31% for thrombolysis. Conclusion. Low flow rates detected using Transonic monitoring were associated with increased thrombosis, while stenosis detected using Duplex ultrasonography was not a strong predictor of incipient thrombosis; however, these different access characteristics were compared using monitoring techniques that may be ideal in different clinical situations.

In the past 15 years, there has been a trend to decrease dialysate calcium concentrations to prevent hypercalcemia. However, low dialysate calcium can provoke hyperparathyroidism. The time course of the effect of increasing dialysate calcium is not well characterized, and the effect on calcium-phosphate product is unclear. Therefore, we studied the effect of increasing dialysate calcium from 1.5 to 1.75 mM in 21 stable patients on hemodialysis who had serum phosphate of less than 2 mM and serum calcium of less than 2.4 mM. Over 10 months, parathyroid hormone levels fell from 39.6 to 16.6 pM (p < 0.0001), whereas serum calcium increased from 2.27 to 2.41 mM. There were no significant changes in serum phosphate or the calcium-phosphate product. Three patients became hypercalcemic when their parathyroid hormone levels were suppressed to less than 10 pM. We conclude that in carefully selected patients, increasing dialysate calcium can safely treat hyperparathyroidism with minimal risk of complications. This treatment has the advantage over the use of vitamin D therapy of being less expensive, independent of patient compliance, and less likely to cause increases in serum phosphate or calcium-phosphate product.

A 42-year-old man with end-stage renal disease (ESRD) was referred for conversion to nocturnal hemodialysis (NHD) therapy from conventional hemodialysis (CHD) therapy because of refractory intermittent claudication secondary to peripheral arterial disease (PAD). The patient was initiated on CHD therapy in 1976 and subsequently had undergone two unsuccessful renal transplantations. While on CHD therapy, his clinical course was complicated by worsening vascular and soft-tissue calcification. Extensive dystrophic soft-tissue calcification was noted bilaterally in his hands, lower extremities, and sacral region, requiring surgical excision. Lower-extremity arterial Doppler scans documented vascular calcification and a pronounced decrease in peripheral arterial flow bilaterally. After conversion to NHD therapy (7.5 h/session five times weekly), the patient became symptom free and had significant clinical improvements in (1) hemodynamics, measured by clinic blood pressure and two-dimensional echocardiography, (2) biochemical profile, and (3) a sustained improvement in arterial Doppler flow measured by duplex Doppler ultrasound. We conclude that NHD was able to improve lower-extremity PAD in our patient. Further observational and interventional studies are required to investigate the therapeutic potential of NHD for the treatment of PAD in patients with ESRD.

Kidney transplantation from living donors is generally a safe, effective form of renal replacement therapy. When evaluating potential living donors and their intended recipients, a careful assessment process is followed in order to ensure that ethical standards are upheld. During this assessment, important medical information with serious consequences, which was not being sought as part of the donor/recipient evaluation, may be discovered. The information may or may not be relevant to the decision to donate. However, such a discovery raises the difficult questions of whether or not there is an obligation to disclose the information, to whom does the information belong, and what process should be used to resolve the issue? We present a case that forced us to confront these questions and raised issues of truth telling, autonomy, paternalism, confidentiality, and the nature of the relationship between patients and health care professionals.

Epilepsy is a debilitating condition affecting 1% of the population worldwide. Medications fail to control seizures in at least 30% of patients, and deep brain stimulation (DBS) is a promising alternative treatment. A modified clinical DBS hardware platform was recently described (PC+S) allowing long-term recording of electrical brain activity such that effects of DBS on neural networks can be examined. This study reports the first use of this device to characterize idiopathic epilepsy and assess the effects of stimulation in a nonhuman primate (NHP). Clinical DBS electrodes were implanted in the hippocampus of an epileptic NHP bilaterally, and baseline local field potential (LFP) recordings were collected for seizure characterization with the PC+S. Real-time automatic detection of ictal events was demonstrated and validated by concurrent visual observation of seizure behavior. Seizures consisted of large-amplitude 8- to 25-Hz oscillations originating from the right hemisphere and quickly generalizing, with an average occurrence of 0.71 ± 0.15 seizures/day. Various stimulation parameters resulted in suppression of LFP activity or in seizure induction during stimulation under ketamine anesthesia. Chronic stimulation in the awake animal was studied to evaluate how seizure activity was affected by stimulation configurations that suppressed broadband LFPs in acute experiments. This is the first electrophysiological characterization of epilepsy using a next-generation clinical DBS system that offers the ability to record and analyze neural signals from a chronically implanted stimulating electrode. These results will direct further development of this technology and ultimately provide insight into therapeutic mechanisms of DBS for epilepsy.

Background Sustained low efficiency dialysis (SLED) is increasingly used as a renal replacement modality in critically ill patients with acute kidney injury (AKI) and hemodynamic instability. SLED may reduce the hemodynamic perturbations of intermittent hemodialysis, while obviating the resource demands of CRRT. Although SLED is being increasingly used, few studies have evaluated its impact on clinical outcomes. Methods We conducted a cohort study comparing SLED (target 8 h/session, blood flow 200 mL/min, predominantly without anticoagulation) to CRRT in four ICUs at an academic medical centre. The primary outcome was mortality 30 days after RRT initiation, adjusted for demographics, comorbidity, baseline kidney function, and Sequential Organ Failure Assessment score. Secondary outcomes were persistent RRT dependence at 30 days and early clinical deterioration, defined as a rise in SOFA score or death 48 h after starting RRT. Results We identified 158 patients who initiated treatment with CRRT and 74 with SLED. Mortality at 30 days was 54 % and 61 % among SLED- and CRRT-treated patients, respectively [adjusted odds ratio (OR) 1.07, 95 % CI 0.56–2.03, as compared with CRRT]. Among SLED recipients, the risk of RRT dependence at 30 days (adjusted OR 1.36, 95 % CI 0.51–3.57) and early clinical deterioration (adjusted OR 0.73, 95 % CI 0.40–1.34) were not different as compared to patients who initiated CRRT. Conclusions Notwithstanding the limitations of this small non-randomized study, we found similar clinical outcomes for patients treated with SLED and CRRT. While we await the completion of a trial that will definitively assess the non-inferiority of SLED as compared to CRRT, SLED appears to be an acceptable alternative form of renal support in hemodynamically unstable patients with AKI. Electronic supplementary material The online version of this article (doi:10.1186/s12882-015-0123-4) contains supplementary material, which is available to authorized users.

Introduction: Vancomycin remains the mainstay in the treatment of meticillin‐resistant Staphylococcus aureus (MRSA) bacteraemia; however, concerns exist about its continued efficacy in the presence of rising MICs. Daptomycin serves as an alternative but has also witnessed increases in reduced susceptibility. Several published case reports have demonstrated the potential utility of ceftaroline as a viable therapeutic option for invasive MRSA infections, including endocarditis. Case presentation: A 23‐year‐old pregnant female presented with complaints of foot pain and fevers up to 104 °F. Her past medical history included polysubstance abuse, hepatitis C, intravenous drug use and a right arm abscess 2 years ago due to MRSA. Daptomycin was started empirically due to an allergy (angioedema) to vancomycin. Blood cultures returned positive for MRSA and remained persistently positive for 10 days at which point ceftaroline was added. Subsequent positive blood cultures on day 12 revealed daptomycin‐non‐susceptible MRSA at an MIC of 4 µg ml–1. Consequently, daptomycin was discontinued and gentamicin was added. Blood cultures were negative by day 14 and the patient completed a total of 2 weeks of gentamicin and 4 weeks of ceftaroline after the first negative blood culture. The baby was born premature at 34 weeks and 2 days due to complications of pregnancy; however, no adverse effects of antimicrobial therapy were noted. Conclusion: We describe the emergence of daptomycin‐non‐susceptibility during treatment and the successful eradication of persistent daptomycin‐non‐susceptible MRSA bacteraemia and endocarditis with a combination of ceftaroline and gentamicin in a pregnant female.