Polyamine biosynthesis and eIF5A hypusination are modulated by the DNA tumor virus KSHV and promote KSHV viral infection.

Polyamines are critical metabolites involved in various cellular processes and often dysregulated in cancers. Kaposi's sarcoma-associated Herpesvirus (KSHV), a defined human oncogenic virus, leads to profound alterations of host metabolic landscape to favor development of KSHV-associated malignancies. In our studies, we identified that polyamine biosynthesis and eIF5A hypusination are dynamically regulated by KSHV infection through modulation of key enzymes (ODC1 and DHPS) of these pathways. During KSHV latency, ODC1 and DHPS are upregulated along with increase of hypusinated eIF5A (hyp-eIF5A), while hyp-eIF5A is further induced along with reduction of ODC1 and intracellular polyamines during KSHV lytic reactivation. In return these metabolic pathways are required for both KSHV lytic reactivation and de novo infection. Further analysis unraveled that synthesis of critical KSHV latent and lytic proteins (LANA, RTA) depends on hypusinated-eIF5A. We also demonstrated that KSHV infection can be efficiently and specifically suppressed by inhibitors targeting these pathways. Collectively, our results illustrated that the dynamic and profound interaction of a DNA tumor virus (KSHV) with host polyamine biosynthesis and eIF5A hypusination pathways promote viral propagation, thus defining new therapeutic targets to treat KSHV-associated malignancies.

Management of Paraneoplastic Syndromes in the Era of Immune Checkpoint Inhibitors.

OPINION STATEMENT: Our understanding of paraneoplastic neurologic syndromes (PNS) has blossomed over the past few decades. Clinicians have access to more robust diagnostic criteria and have a heightened index of suspicion for these disorders. Nonetheless, treatment, which typically includes immunosuppression, and response to treatment, varies. Due to persistent difficulty in making a definitive diagnosis, we favor empiric treatment when a possible diagnosis of PNS is suspected, and other alternative causes have substantially been excluded (e.g., infections, toxic-metabolic derangements, metastasis, or leptomeningeal disease). Treatment of the underlying cancer, if identified, is the first therapeutic step and can prevent disease worsening and in rare cases, can reverse neurologic symptoms. In addition to anti-cancer treatment, first line immunotherapies, which include corticosteroids, intravenous immunoglobulins (IVIG), or plasma exchange (PLEX) are typically used. If partial or no benefit is seen, second line immunotherapeutic agents such as rituximab are considered. Additionally, the severity of the initial presentation and possible risk for relapse influences the use of the latter agents. Symptomatic management is also an important component in our practice and will depend on the syndrome being treated. One of the more novel entities we are facing currently is the management of immune checkpoint (ICI)-induced PNS. In those cases, current American Society of Clinical Oncology (ASCO) guidelines are followed.

Reclassifying guesses to increase signal-to-noise ratio in psychological experiments.

This paper introduces a novel procedure that can increase the signal-to-noise ratio in psychological experiments that use accuracy as a selection variable for another dependent variable. This procedure relies on the fact that some correct responses result from guesses and reclassifies them as incorrect responses using a trial-by-trial reclassification evidence such as response time. It selects the optimal reclassification evidence criterion beyond which correct responses should be reclassified as incorrect responses. We show that the more difficult the task and the fewer the response alternatives, the more to be gained from this reclassification procedure. We illustrate the procedure on behavioral and ERP data from two different datasets (Caplette et al. NeuroImage 218, 116994, 2020; Faghel-Soubeyrand et al. Journal of Experimental Psychology: General 148, 1834-1841, 2019) using response time as reclassification evidence. In both cases, the reclassification procedure increased signal-to-noise ratio by more than 13%. Matlab and Python implementations of the reclassification procedure are openly available ( https://github.com/GroupeLaboGosselin/Reclassification ).

Suspected medullary washout leading to severe polyuria following delayed cerebral ischemia: a case report.

BACKGROUND: Delayed cerebral ischemia is a clinical entity commonly encountered in patients presenting with acute neurological injury and is often complicated by dysnatremias, such as the cerebral salt wasting syndrome. In this case report, we described an exceptional case of polyuria attributed to an initial cerebral salt wasting phenomenon and iatrogenic-induced medullary washout. CASE PRESENTATION: A 53-year-old woman was admitted to our hospital for the management of a Modified Fisher scale grade 4 subarachnoid hemorrhage due to a ruptured posterior communicating aneurysm. She was initially managed with coil embolization and external ventricular drain due to secondary hydrocephalus. Throughout the course of her hospitalization, she developed severe polyuria reaching up to 40L per day. To keep up with the excessive urinary losses and maintain appropriate cerebral perfusion, fluid replacement therapy was adjusted every hour, reaching up to 1.3 L of crystalloid per hour in addition to aminergic support. An initial diagnosis of partial diabetes insipidus, followed by a cerebral salt wasting syndrome was suspected. While the urine output continued to increase, her serum urea concentration progressively decreased to a point of almost being undetectable on day 9. At that time, the presence of an interstitial medulla washout was hypothesized. Various pharmacological and non-pharmacological interventions were progressively introduced to regain normal renal homeostasis, including non-steroidal anti-inflammatory drugs, fludrocortisone, oral urea and high-protein intake. Medications were progressively weaned, and the patient was successfully discharged from the ICU. CONCLUSIONS: Cerebral salt wasting should be considered in the initial differential diagnosis of a patient presenting with polyuria in the context of acute neurological injury. Early recognition of this entity is critical to quickly implement proper management. However, as shown in this case report, the concomitance of delayed cerebral ischemia may complexify that management.

Urinary biomarkers predict progression and adverse outcomes of acute kidney injury in critical illness.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients and is associated with high morbidity and mortality. The Dublin Acute Biomarker Group Evaluation study is a prospective cohort study of critically ill patients (n = 717). We hypothesized that novel urinary biomarkers would predict progression of AKI and associated outcomes. METHODS: The primary (diagnostic) analysis assessed the ability of biomarkers levels at the time of early Stage 1 or 2 AKI to predict progression to higher AKI stage, renal replacement therapy (RRT) or death within 7 days of intensive care unit admission. In the secondary (prognostic) analysis, we investigated the association between biomarker levels and RRT or death within 30 days. RESULTS: In total, 186 patients had an AKI within 7 days of admission. In the primary (diagnostic) analysis, 8 of the 14 biomarkers were independently associated with progression. The best predictors were cystatin C [adjusted odds ratio (aOR) 5.2; 95% confidence interval (CI) 1.3-23.6], interleukin-18 (IL-18; aOR 5.1; 95% CI 1.8-15.7), albumin (aOR 4.9; 95% CI 1.5-18.3) and neutrophil gelatinase-associated lipocalin (NGAL; aOR 4.6; 95% CI 1.4-17.9). Receiver-operating characteristics and net reclassification index analyses similarly demonstrated improved prediction by these biomarkers. In the secondary (prognostic) analysis of Stages 1-3 AKI cases, IL-18, NGAL, albumin and monocyte chemotactic protein-1 were also independently associated with RRT or death within 30 days. CONCLUSIONS: Among 14 novel urinary biomarkers assessed, cystatin C, IL-18, albumin and NGAL were the best predictors of Stages 1-2 AKI progression. These biomarkers, after further validation, may have utility to inform diagnostic and prognostic assessment and guide management of AKI in critically ill patients.

Hepatitis B, C, and delta in the general population in Mayotte: hepatitis B as a major public health concern.

BACKGROUND: Located in southwestern Indian Ocean, Mayotte is a French territory, with a very specific demographic, social and health context. To date, epidemiological data on infections by hepatitis B (HBV), C (HCV), and delta (HDV) viruses in Mayotte have been sparse. We aimed to estimate, in the 15-69-year-old general population living in Mayotte, the prevalence of infections by hepatitis B (HBV), C (HCV), and delta (HDV) viruses and the distribution of HBV status: current infection with positive HBs antigen (Ag); resolved infection with positive HBc antibodies and negative HBsAg; immunisation by vaccination with only positive HBs antibodies; and no infection/no immunisation with negative markers. We also described the characteristics of infected people and assessed the determinants of lifetime HBV infection. METHODS: The Unono Wa Maore survey, implemented in a random sample of the general population in 2018-2019, consisted of an at-home collection of epidemiological data and venous blood samples. Detection of hepatitis B, C, and delta serological and molecular markers was performed. RESULTS: Among 5207 eligible people, 4643 responded to the questionnaire (89.2%), with 2917 being tested for HBV and HCV (62.8%). Estimated HBV status was as follows: current infection 3.0% (95% confidence interval [CI]: 2.3-3.9%) (n = 76); resolved infection 27.8% (95% CI: 25.8-29.9); immunisation by vaccination 27.7% (95% CI: 25.9-29.7); and no infection/no immunisation 41.5% (95% CI: 39.3-43.7). One participant was positive for HDV antibodies (Ab) (0.65%) with a negative HDV-RNA viral load. The risk of lifetime HBV infection was higher in men (adjusted prevalence ratio (aPR): 1.55, 95% CI: 1.29-1.89); in people aged 30-49 years (aPR: 3.83, 95% CI: 1.49-9.81) or 50-69 years (aPR: 4.52, 95% CI: 1.77-11.53) compared to those under 20; in individuals who reported no condom use during their first sexual intercourse (aPR: 1.46, 95% CI: 1.01-2.14); and in those living in Dembeni-Mamoudzou (aPR: 1.40, 95% CI: 1.09-1.80) compared to the West-Centre of Mayotte. Finally, six individuals were positive for HCV antibodies (0.21%), including three positive for HCV RNA. CONCLUSIONS: Mayotte is an area of intermediate endemicity for HBV and low endemicity for HCV and HDV. With a prevalence of HBsAg 10 times higher than in mainland France, a high proportion of people susceptible to HBV infection, and a demographic, health, and social context that may favour its transmission, hepatitis B is a major public health concern in Mayotte.

Intermittent Convective Therapies in Patients with Acute Kidney Injury: A Systematic Review with Meta-Analysis.

INTRODUCTION: In critically ill patients requiring intermittent renal replacement therapy (RRT), the benefits of convective versus diffusive clearance remain uncertain. We conducted a systematic review and meta-analysis to determine the safety, clinical efficacy, and clearance efficiency of hemofiltration (HF) and hemodiafiltration (HDF) compared to hemodialysis (HD) in patients with acute kidney injury (AKI) receiving intermittent RRT. METHOD: We searched Medline, Embase, Cochrane Library, and PROSPERO. We included clinical trials and observational studies that reported the use of intermittent HF or HDF in adult patients with AKI. The following outcomes were included: mortality, renal recovery, clearance efficacy, intradialytic hemodynamic stability, circuit loss, and inflammation modulation. RESULTS: A total of 3,169 studies were retrieved and screened. Four randomized controlled trials and 4 observational studies were included (n: 615 patients). Compared with conventional HD, intermittent convective therapies had no effect on in-hospital mortality (relative risk, 1.23; 95% confidence interval (CI), 0.76-1.99), renal recovery at 30 days (RR, 0.98; 95% CI, 0.82-1.16), time-to-renal recovery (mean difference [MD], 0.77; 95% CI, -6.56 to 8.10), and number of dialysis sessions until renal recovery (MD, -1.34; 95% CI, -3.39 to 0.72). The overall quality of included studies was low, and dialysis parameters were suboptimal for all included studies. CONCLUSION: This meta-analysis suggests that there is no significant difference in short-term mortality and renal recovery in patients with severe AKI when treated with intermittent HF or HDF compared to conventional HD. This systematic review emphasizes the need for further trials evaluating optimal convective parameters in AKI patients treated with intermittent dialysis.

Epidemiological profile of COVID-19 in the French overseas department Mayotte, 2020 to 2021.

BackgroundDuring the COVID-19 pandemic, national and local measures were implemented on the island of Mayotte, a French overseas department in the Indian Ocean with critical socioeconomic and health indicators.AimWe aimed to describe the COVID-19 outbreak in Mayotte from March 2020 to March 2021, with two waves from 9 March to 31 December 2020 and from 1 January to 14 March 2021, linked to Beta (20H/501Y.V2) variant.MethodsTo understand and assess the dynamic and the severity of the COVID-19 outbreak in Mayotte, surveillance and investigation/contact tracing systems were set up including virological, epidemiological, hospitalisation and mortality indicators.ResultsIn total, 18,131 cases were laboratory confirmed, with PCR or RAT. During the first wave, incidence rate (IR) peaked in week 19 2020 (133/100,000). New hospitalisations peaked in week 20 (54 patients, including seven to ICU). Testing rate increased tenfold during the second wave. Between mid-December 2020 and mid-January 2021, IR doubled (851/100,000 in week 5 2021) and positivity rate tripled (28% in week 6 2021). SARS-CoV-2 Beta variant (Pangolin B.1.351) was detected in more than 80% of positive samples. Hospital admissions peaked in week 6 2021 with 225 patients, including 30 to ICU.ConclusionThis massive second wave could be linked to the high transmissibility of the Beta variant. The increase in the number of cases has naturally led to a higher number of severe cases and an overburdening of the hospital. This study shows the value of a real-time epidemiological surveillance for better understanding crisis situations.

Nephrotoxicity from Vancomycin Combined with Piperacillin-Tazobactam: A Comprehensive Review.

BACKGROUND: Recent studies have identified the combination of vancomycin with piperacillin-tazobactam (VPT) to be associated with increased nephrotoxicity. Multiple, large cohort studies have found this widely used combination to have a higher risk of nephrotoxicity than other regimens in a variety of populations. SUMMARY: This review summarizes the epidemiology and clinical features of VPT-associated acute kidney injury (AKI). Potential mechanisms involved in the pathogenesis of this phenomenon are also discussed. Key Message: VPT-associated nephrotoxicity is a recently recognized clinical entity. Clinical strategies to minimize the risk of toxicity in this setting include antimicrobial stewardship, monitoring of kidney function, and emerging data supporting the potential role for novel biomarkers in predicting and managing AKI.

A CRISPR/Cas9 screen identifies the histone demethylase MINA53 as a novel HIV-1 latency-promoting gene (LPG).

Although combination antiretroviral therapy is potent to block active replication of HIV-1 in AIDS patients, HIV-1 persists as transcriptionally inactive proviruses in infected cells. These HIV-1 latent reservoirs remain a major obstacle for clearance of HIV-1. Investigation of host factors regulating HIV-1 latency is critical for developing novel antiretroviral reagents to eliminate HIV-1 latent reservoirs. From our recently accomplished CRISPR/Cas9 sgRNA screens, we identified that the histone demethylase, MINA53, is potentially a novel HIV-1 latency-promoting gene (LPG). We next validated MINA53's function in maintenance of HIV-1 latency by depleting MINA53 using the alternative RNAi approach. We further identified that in vitro MINA53 preferentially demethylates the histone substrate, H3K36me3 and that in cells MINA53 depletion by RNAi also increases the local level of H3K36me3 at LTR. The effort to map the downstream effectors unraveled that H3K36me3 has the cross-talk with another epigenetic mark H4K16ac, mediated by KAT8 that recognizes the methylated H3K36 and acetylated H4K16. Removing the MINA53-mediated latency mechanisms could benefit the reversal of post-integrated latent HIV-1 proviruses for purging of reservoir cells. We further demonstrated that a pan jumonji histone demethylase inhibitor, JIB-04, inhibits MINA53-mediated demethylation of H3K36me3, and JIB-04 synergizes with other latency-reversing agents (LRAs) to reactivate latent HIV-1.

Rift Valley Fever Outbreak, Mayotte, France, 2018-2019.

From November 2018 through July 2019, an outbreak of Rift Valley fever in humans occurred in Mayotte, France; 142 cases were confirmed. Exposure to animals or their biological fluid was reported by 73% of patients. Health authorities have been implementing control measures, including veterinary surveys, vector control interventions, and prevention measures.

New drugs for acute kidney injury.

PURPOSE OF REVIEW: To describe recent advances in the development of therapeutic agents for acute kidney injury (AKI). RECENT FINDINGS: Traditional care for AKI is mostly supportive. At present, no specific therapy has been developed to prevent or treat AKI. However, based on a better understanding of the pathophysiology of AKI, various potential compounds have been recently identified and tested. A variety of pathways has been targeted, including oxidative and mitochondrial stress, cellular metabolism and repair, inflammation, apoptosis and hemodynamics. Many of these potential agents are currently ongoing early-phase clinical trials, and the purpose of this review is to provide a summary of those with the most potential. SUMMARY: Despite the lack of therapies specifically approved for AKI, many interesting potential agents are entering clinical trials, with the potential to transform the care of patients with AKI.

Curaxin CBL0137 has the potential to reverse HIV-1 latency.

A cure for human immunodeficiency virus type-1 (HIV-1) has been hampered by the limitation of current combination antiretroviral therapy (cART) to address the latent reservoirs in HIV-1 patients. One strategy proposed to eradicate these reservoirs is the "shock and kill" approach, where latency-reversing agents (LRAs) are used to reactivate and promote viral cell death and/or immune killing of reactivated cells. Here, we report that curaxin CBL0137, an antitumor compound, can potentiate tumor necrosis factor-α-mediated reactivation of latently infected HIV-1cell lines. Additionally, the single use of CBL0137 is sufficient to reactivate HIV-1 latent reservoirs in peripheral mononuclear cells (PBMCs) isolated from HIV-1 positive, cART-treated, aviremic patients. Thus, CBL0137 possesses capabilities as a LRA and could be considered for the "shock and kill" approach.

Performance of Day 5 KIDScore™ morphokinetic prediction models of implantation and live birth after single blastocyst transfer.

PURPOSE: While several studies reported the association between morphokinetic parameters and implantation, few predictive models were developed to predict implantation after day 5 embryo transfer, generally without external validation. The objective of this study was to evaluate the respective performance of 2 commercially available morphokinetic-based models (KIDScore™ Day 5 versions 1 and 2) for the prediction of implantation and live birth after day 5 single blastocyst transfer. METHODS: This monocentric retrospective study was conducted on 210 ICSI cycles with single day 5 embryo transfer performed with a time-lapse imaging (TLI) system between 2013 and 2016. The association between both KIDScore™ and the observed implantation and live birth rates was calculated, as well as the agreement between embryologist's choice for transfer and embryo ranking by the models. RESULTS: Implantation and live birth rate were both 35.7%. A significant positive correlation was found between both models and implantation rate (r = 0.96 and r = 0.90, p = 0.01) respectively. Both models had statistically significant but limited predictive power for implantation (AUC 0.60). There was a fair agreement between the embryologists' choice and both models (78% and 61% respectively), with minor differences in case of discrepancies. CONCLUSIONS: KIDScore™ Day 5 predictive models are significantly associated with implantation rates after day 5 single blastocyst transfer. However, their predictive performance remains perfectible. The use of these predictive models holds promises as decision-making tools to help the embryologist select the best embryo, ultimately facilitating the implementation of SET policy. However, embryologists' expertise remains absolutely necessary to make the final decision.

Collagen regeneration template in the management of full-thickness wounds: a prospective multicentre study.

OBJECTIVE: To evaluate the tolerance and healing rate of a collagen regeneration template in covering full-thickness wounds, including rate of adverse events. METHOD: In this prospective, multicentre study, patients with a full-thickness wound underwent two-stage surgery consisting of implantation of a collagen regeneration template followed by a split-thickness skin graft (STSG). Patients were followed-up for 12 months. Adverse events arising from either the implantation or STSG were evaluated. RESULTS: Of the 33 patients included in the study, 29 completed the full follow-up period. During the study, 13 adverse events occurred at the treated wound site, as reported by 11 patients during follow-up. These included local infection (n=5), a diffuse infection (n=1) and non-infectious seroma under the silicon layer (n=1). The mean percentage of take of the collagen template at 21±7 days after implantation was 81.2% of the treated surface. The mean percentage of take of STSG at 28 days after grafting was 84.4% of grafted surface. STSG was successful in 28 patients, but was completely rejected at 12 months for one patient. Mean functional score at 12 months, as evaluated by the treating surgeons, was 76.8/100 and mean aesthetic score was 62.7/100. CONCLUSION: This study found use of a collagen regeneration template to be a safe procedure for the coverage of full thickness-wounds.

Specificity of process analytical tools in the monitoring of multicomponent pharmaceutical powders.

The application of Process Analytical Technologies in pharmaceutical manufacturing has been the subject of many studies. Active pharmaceutical ingredient monitoring in real time throughout the manufacturing process is commonly the target of many such implementations. The tools in place must be sensitive to, and selective of, the parameter(s) to be monitored, i.e. in the case of component quantification, they must respond to the component in question and be robust against all others. In this study, four different ingredients (riboflavin, ferrous fumarate, ginseng, and ascorbic acid) in a multi-component blend were monitored by three different tools (near infrared spectroscopy, laser-induced fluorescence and red-green-blue camera) using a full factorial design. The goal was to develop efficient and robust concentration-reading/prediction models able to assess and monitor component interference. Despite relatively high complexity of the blend studied, the three tools demonstrated reasonable specificity for the tracked ingredients (and showed advantages when combined), taking into account larger acceptance criteria typical of dietary products. In certain cases, some interference might lead to biased predictions, highlighting the importance of good calibration. The tools tested and the methodology proposed has divulged their potential in monitoring these components, despite the complexity of the 31-component blend.

Monitoring the concentration of flowing pharmaceutical powders in a tableting feed frame.

The use of process analytical technology (PAT) tools is increasing steadily in the pharmaceutical industry. Such tools are now located throughout the process. When producing tablets, the tableting step itself may be the ideal moment to assess final product composition. Being the last unit operation in tablet production where the elements are still free flowing, it is relatively straightforward to ascertain the composition of the blend in real time. However, a single probe cannot be expected to monitor the composition of every component of a multicomponent blend. In this study, three PAT tools (light-induced fluorescence spectroscopy, near-infrared spectroscopy and color (RGB) imaging) simultaneously checked the composition of powder blends flowing through the feeding unit (feed frame) of a tablet press. The results demonstrate the potential of these tools in monitoring changes in the concentration of a multicomponent mixture in real time, providing users with means to both scrutinize the process and better understand phenomena occurring inside the feed frame.

The effect of different lumbar belt designs on the lumbopelvic rhythm in healthy subjects.

BACKGROUND: Research suggests that in some patients with low back pain, lumbar belts (LB) may derive secondary prophylactic benefits. It remains to be determined, however, which patients are most likely to benefit from prophylactic LB use, and which LB design is optimal for this purpose. The objective of this study was to determine the effect of different lumbar belts designs on range of motion and lumbopelvic rhythm. METHODS: Healthy subjects (10 males; 10 females) performed five standing lumbar flexion/extension cycles, with knees straight, during a control (no belt) and four lumbar belt experimental conditions (extensible, with and without dorsal and ventral panels; non-extensible). Motion of the pelvis and lumbar spine was measured with 3D angular inertial sensors. RESULTS: The results suggest that adding dorsal and ventral panels to an extensible LB produces the largest lumbar spine restrictions among the four tested lumbar belt designs, which in turn also altered the lumbopelvic rhythm. On a more exploratory basis, some sex differences were seen and the sex × experimental condition interaction just failed to reach significance. CONCLUSIONS: LB may provide some biomechanical benefit for patients with low back disorders, based on the protection that may be provided against soft tissue creep-based injury mechanisms. More comprehensive assessment of different LB designs, with additional psychological and neuromuscular measurement outcomes, however, must first be conducted in order to produce sound recommendations for LB use. Future research should also to take sex into account, with sufficient statistical power to clearly refute or confirm the observed trends.

2023 French recommendations for diagnosing and managing prepatellar and olecranon septic bursitis.

Septic bursitis (SB) is a common condition accounting for one third of all cases of inflammatory bursitis. It is often related to professional activities. Management is heterogeneous and either ambulatory or hospital-based, with no recommendations available. This article presents recommendations for managing patients with septic bursitis gathered by 18 rheumatologists from the French Society for Rheumatology work group on bone and joint infections, 1 infectious diseases specialist, 2 orthopedic surgeons, 1 general practitioner and 1 emergency physician. This group used a literature review and expert opinions to establish 3 general principles and 11 recommendations for managing olecranon and prepatellar SB. The French Health authority (Haute Autorité de santé [HAS]) methodology was used for these recommendations. Designed for rheumatologists, general practitioners, emergency physicians and orthopedic surgeons, they focus on the use of biological tests and imaging in both outpatient and inpatient management. Antibiotic treatment options (drugs and duration) are proposed for both treatment modalities. Finally, surgical indications, non-drug treatments and prevention are covered by specific recommendations.

The utility of magnetoencephalography in the presurgical evaluation of refractory insular epilepsy.

PURPOSE: To study the utility of magnetoencephalography (MEG) in patients with refractory insular epilepsy. Covered by highly functional temporal, frontal, and parietal opercula, insular-onset seizures can manifest a variety of ictal symptoms falsely leading to a diagnosis of temporal, frontal, or parietal lobe seizures. Lack of recognition of insular seizures may be responsible for some epilepsy surgery failures. METHODS: We retrospectively reviewed and analyzed MEG data in 14 patients with refractory insular seizures defined through intracranial electroencephalography (EEG) or by the presence of an epileptogenic lesion in the insula with compatible seizure semiology. MEG was performed as part of the noninvasive presurgical evaluation, using a 275-channel whole head MEG system. MEG data were analyzed using a single equivalent current dipole model. MEG localization was compared to interictal positron emission tomography (PET) and ictal single photon emission computed tomography (SPECT) results and to the resection margin. KEY FINDINGS: Three patterns of MEG spike sources were observed. Seven patients showed an anterior operculoinsular clusters and two patients had a posterior operculoinsular cluster. No spikes were detected in one patient, and the remaining four patients showed a diffuse perisylvian distribution. Spike sources showed uniform orientation perpendicular to the sylvian fissure. Nine patients proceeded to insular epilepsy surgery with favorable surgical outcome. Among patients with anterior operculoinsular cluster who proceeded to have surgery, MEG provided superior information to ictal SPECT in four of six patients and to interictal PET in five of six patients. SIGNIFICANCE: MEG is useful in identifying patients who are likely to benefit from epilepsy surgery targeting the insula, particularly if a tight dipole cluster is identified even if other noninvasive modalities fail to produce localizing results.