Search

Objective: Multiple single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D) susceptibility have been identified in predominantly European-derived populations. These SNPs have not been extensively investigated for individual and cumulative effects on T2D risk in African Americans.Research Design and Methods: Seventeen index T2D risk variants were genotyped in 2,652 African American case subjects with T2D and 1,393 nondiabetic control subjects. Individual SNPs and cumulative risk allele loads were assessed for association with risk for T2D. Cumulative risk was assessed by counting risk alleles and evaluating the difference in cumulative risk scores between case subjects and control subjects. A second analysis weighted risk scores (ln [OR]) based on previously reported European-derived effect sizes.Results: Frequencies of risk alleles ranged from 8.6 to 99.9%. Eleven SNPs had ORs >1, and 5 from ADAMTS9, WFS1, CDKAL1, JAZF1, and TCF7L2 trended or had nominally significant evidence of T2D association (P < 0.05). Individuals carried between 13 and 29 risk alleles. Association was observed between T2D and increase in risk allele load (unweighted OR 1.04 [95% CI 1.01-1.08], P = 0.010; weighted 1.06 [1.03-1.10], P = 8.10 × 10(-5)). When TCF7L2 SNP rs7903146 was included as a covariate, the risk score was no longer associated with T2D in either model (unweighted 1.02 [0.98-1.05], P = 0.33; weighted 1.02 [0.98-1.06], P = 0.40).Conclusions: The trend of increase in risk for T2D with increasing risk allele load is similar to observations in European-derived populations; however, these analyses indicate that T2D genetic risk is primarily mediated through the effect of TCF7L2 in African Americans. [ABSTRACT FROM AUTHOR]

Context: Protein kinase C-beta (PKC-beta) is a cell-signaling intermediate implicated in development of diabetic complications.Objective: To examine the risk association of PKC-beta 1 gene (PRKCB1) polymorphisms and end-stage renal disease (ESRD) in an 8-year prospective cohort of Chinese patients with type 2 diabetes.Design, Setting, and Participants: We genotyped 18 common tag single-nucleotide polymorphisms (SNPs) that span the PRKCB1 gene (r(2) = 0.80) in 1172 Chinese patients (recruited 1995-1998) without renal disease at baseline. A validation cohort included an additional 1049 patients with early-onset diabetes who were free of renal disease at baseline and were recruited after 1998.Main Outcome Measures: Associations of PRKCB1 polymorphisms under additive, dominant, and recessive genetic models with new onset of ESRD (defined as estimated glomerular filtration rate <15 mL/min/1.73 m(2) or dialysis or renal-related death) were assessed by Cox proportional hazard regression, adjusted for all conventional risk factors including use of medications.Results: After a mean (SD) of 7.9 (1.9) years, 90 patients (7.7%) progressed to ESRD. Four common SNPs were associated with ESRD (P < .05). The closely linked T allele at rs3760106 and G allele rs2575390 (r(2) = 0.98) showed the strongest association with ESRD (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.31-3.87; P = .003, and HR, 2.26; 95% CI, 1.31-3.88; P = .003, respectively). Four common variants predicted ESRD in separate models. The HR for ESRD increased with increasing number of risk alleles (P < .001) in the joint effect analysis. The adjusted risk for ESRD was 6.04 (95% CI, 2.00-18.31) for patients with 4 risk alleles compared with patients with 0 or 1 risk allele. Incidence was 4.4 per 1000 person-years (95% CI, 0.5-8.2) among individuals with 0 or 1 risk allele compared with 20.0 per 1000 person-years (95% CI, 8.8-31.1) in those carrying 4 risk alleles (6.9% of the cohort). These results were validated in a separate prospective cohort of young-onset diabetic patients. Of 1049 patients in the validation cohort, 151 (14.3%) developed chronic kidney disease (CKD) during follow-up, and there were significant associations between both the T allele of rs3760106 and the G allele of rs2575390 and development of CKD (HR, 1.68; 95% CI, 1.10-2.57; P = .02, and HR, 1.62; 95% CI, 1.07-2.47; P = .02, respectively).Conclusion: Genetic variants in the PRKCB1 gene were independently associated with development of ESRD in Chinese patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether diffusion abnormalities can be observed in nonsymptomatic family members with a known causative Cu/Zn superoxide dismutase mutation (asymptomatic familial amyotrophic lateral sclerosis; AFALS(+SOD1)) in a family with autosomal dominant familial amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI). Materials and Methods: A total of eight AFALS(+SOD1) subjects (aged 17-43 years) were age-matched with 13 healthy controls (aged 19-45 years) without SOD1 mutations. DTI was carried out on a 1.5T scanner. The diffusion index maps derived were then normalized spatially for voxel-based analysis. region of interest (ROI)-based analysis was also carried out. Results: Our voxel-based and ROI-based analysis showed that AFALS(+SOD1) subjects have decreased fractional anisotropy (FA) (0.5401 vs. 0.5168, P < 0.05) and increased tensor trace (TT) (2.5854 x 10(-3) mm(2)/second vs. 2.6226 x 10(-3) mm(2)/second, P < 0.04) at the posterior limb of the internal capsule compared to the control subjects. Increased radial diffusivity (E((2,3)/2)) was detected on both sides (right = 0.5710 x 10(-3) mm(2)/second vs. 0.5943 x 10(-3) mm(2)/second, P < 0.05; left = 0.5666 x 10(-3) mm(2)/second vs. 0.5872 x 10(-3) mm(2)/second, P < 0.05). No significant change in axial diffusivity (E(1)) was detected. Conclusion: Abnormal diffusivity was found at the posterior limb of the internal capsule in AFALS(+SOD1) subjects, hitherto unreported. Our results suggest that DTI may detect diffusion abnormalities in AFALS(+SOD1) subjects before symptoms develop. [ABSTRACT FROM AUTHOR]

Mutations in the LMNA gene (encoding lamin A/C) underlie familial partial lipodystrophy, a syndrome of monogenic insulin resistance and diabetes. LMNA maps to the well-replicated diabetes-linkage region on chromosome 1q, and there are reported associations between LMNA single nucleotide polymorphisms (SNPs) (particularly rs4641; H566H) and metabolic syndrome components. We examined the relationship between LMNA variation and type 2 diabetes (using six tag SNPs capturing >90% of common variation) in several large datasets. Analysis of 2,490 U.K. diabetic case and 2,556 control subjects revealed no significant associations at either genotype or haplotype level: the minor allele at rs4641 was no more frequent in case subjects (allelic odds ratio [OR] 1.07 [95% CI 0.98-1.17], P = 0.15). In 390 U.K. trios, family-based association analyses revealed nominally significant overtransmission of the major allele at rs12063564 (P = 0.01), which was not corroborated in other samples. Finally, genotypes for 2,817 additional subjects from the International 1q Consortium revealed no consistent case-control or family-based associations with LMNA variants. Across all our data, the OR for the rs4641 minor allele approached but did not attain significance (1.07 [0.99-1.15], P = 0.08). Our data do not therefore support a major effect of LMNA variation on diabetes risk. However, in a meta-analysis including other available data, there is evidence that rs4641 has a modest effect on diabetes susceptibility (1.10 [1.04-1.16], P = 0.001). [ABSTRACT FROM AUTHOR]

Though unified by challenges in the treatment of status epilepticus (SE), rural Canada is simultaneously massive and diverse, spanning the Pacific, Atlantic, and Arctic Oceans. According to the national statistical agency, the most rural jurisdiction in Canada is the Arctic territory of Nunavut. In particular, the Kivalliq region of Nunavut represents a unique epidemiologic SE space because any treatment beyond typical first-line lorazepam and second-line phenytoin by a non-neurologist locum tenens requires airborne evacuation over a thousand kilometers away to a single hospital with a single electroencephalographic (EEG) laboratory. This distinctive mode of healthcare delivery affords unique insights into the challenges of treating SE in rural Canada, such as lack of EEG infrastructure, a markedly high incidence of SE, the struggles of enduring cultural and socioeconomic trauma, and a relative lack of local epilepsy care as recommended by the World Health Organization. For example, despite empiric treatment and waiting over 2 days on average for EEG, 1 in 5 patients still had ongoing or possible electrographic seizures. At the same time, Kivalliq experiences routine dramatic changes in light-dark exposure each year to afford unique insights into circannual SE chronobiology in relation to the chief human zeitgeber of sunlight. This shows that challenges may also represent opportunities, such as for existing and emerging technologies to synergistically address enormous treatment gaps to improve SE care for the people of Kivalliq, while providing novel insights that may also help improve SE clinical care around the world., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Study Objectives: Seizures are rare in rapid eye movement sleep (REM). However; seizures sometimes occur in REM, and a small number of focal epilepsy patients display their maximum rate of interictal epileptiform discharges in REM. We sought to systematically identify and characterize seizures in REM., Methods: We reviewed all admissions to the Epilepsy Monitoring Unit (EMU) at the Winnipeg Health Sciences Centre over 12-months in 2014-2015. American Academy of Sleep Medicine sleep-stage scoring was initially applied in the standard 30-second epochs. Then, to capture sudden changes in sleep-wake state on shorter timescales that are associated with seizure formation and propagation, we re-scored ictal and peri-ictal EEG epochs every 1 second. Patients found to have seizures in REM were subject to chart review spanning three years pre- and post-admission., Results: REM seizures occurred in 3/63 EMU patients. Notably, one patient exhibited continuous epileptiform activity, consistent with focal nonconvulsive electrographic status epilepticus, throughout REM cycles for each night of her admission. Otherwise, discrete REM seizures constituted a small fraction of the other patients' total seizures (range 5.0-8.3%), occurred shortly after REM onset from non-REM 2, and were manifest as minor epileptic arousals., Conclusions: Our results confirm that REM seizures are rare, while highlighting outliers who widen the known spectrum of heterogeneous sleep effects on seizures/epilepsy. We also report the first case of paradoxical status epilepticus in REM., (© 2024 American Academy of Sleep Medicine.)

Background and Aims: Peritoneal metastasis (PM) in gastric cancer (GC) is associated with poor prognosis and significant morbidity. We sought to understand the genomic, transcriptomic, and tumor microenvironment (TME) features that contribute to peritoneal organotropism in GC., Methods: We conducted a comprehensive multi-omic analysis of 548 samples from 326 patients, including primary tumors, matched normal tissues; peritoneal metastases, and adjacent-normal peritoneal tissues. We used whole exome sequencing, whole transcriptome sequencing, and digital spatial profiling to investigate molecular alterations, gene expression patterns, and TME characteristics associated with PM., Results: Our analysis identified specific genomic alterations in primary tumors, including mutations in ELF3, CDH1, and PIGR, and TME signatures, such as stromal infiltration and M2 macrophage enrichment, associated with increased risk of PM. We observed distinct transcriptional programs and immune compositions in GCPM compared with liver metastases, highlighting the importance of the TME in transcoelomic metastasis. We found differential expression of therapeutic targets between primary tumors and PM, with lower CLDN18.2 and FGFR2b expression in PM. We unravel the roles of the TME in niche reprogramming within the peritoneum, and provide evidence of pre-metastatic niche conditioning even in early GC without clinical PM. These findings were further validated using a humanized mouse model, which demonstrated niche remodeling in the peritoneum during transcoelomic metastasis., Conclusion: Our study provides a comprehensive molecular characterization of GCPM and unveils key biological principles underlying transcoelomic metastasis. The identified predictive markers, therapeutic targets, and TME alterations offer potential avenues for targeted interventions and improved patient outcomes., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medication (ASM) use during pregnancy., Methods: We searched seven databases, from inception to 23 March 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASM class analysis, within epilepsy group analysis and polytherapy compared to monotherapy., Results: We screened 15 720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95% CI 1.18 to 1.50, I 2 74%), LBW RR 1.54 (95% CI 1.33 to 1.77, I 2 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95% CI -161.03 to -76.71, I 2 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASM class analysis were also associated with an increased risk of SGA and LBW., Conclusions: This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASM risks., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Recently, we showed that high-definition transcranial direct current stimulation (hd-tDCS) can acutely reduce epileptic spike rates during and after stimulation in refractory status epilepticus (RSE), with a greater likelihood of patient discharge from the intensive care unit compared to historical controls. We investigate whether electroencephalographic (EEG) desynchronization during hd-tDCS can help account for observed anti-epileptic effects. Defining desynchronization as greater power in higher frequencies such as above 30 ​Hz ("gamma") and lesser power in frequency bands lower than 30 ​Hz, we analyzed 27 EEG sessions from 10 RSE patients who had received 20-minute session(s) of 2-milliamperes of transcranial direct current custom-targeted at the epileptic focus as previously determined by a clinical EEGer monitoring the EEG in real-time. During hd-tDCS, median relative power change over the EEG electrode chains in which power changes were maximal was +4.84%, -5.25%, -1.88%, -1.94%, and +4.99% for respective delta, theta, alpha, beta, and gamma frequency bands in the bipolar longitudinal montage (p ​= ​0.0001); and +4.13%, -5.44%, -1.81%, -3.23%, and +5.41% in the referential Laplacian montage (p ​= ​0.0012). After hd-tDCS, median relative power changes reversed over the EEG electrode chains in which power changes were maximal: -2.74%, +4.20%, +1.74%, +1.75%, and -4.68% for the respective delta, theta, alpha, beta, and gamma frequency bands in the bipolar longitudinal montage (p ​= ​0.0001); and +1.59%, +5.07%, +1.74%, +2.40%, and -5.12% in the referential Laplacian montage (p ​= ​0.0004). These findings are consistent with EEG desynchronization through theta-alpha-beta-gamma bands during hd-tDCS, helping account for the efficacy of hd-tDCS as an emerging novel anti-epileptic therapy against RSE., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Subclinical seizures are common in hospitalized patients and require electroencephalography (EEG) for detection and intervention. At our institution, continuous EEG (cEEG) is not available, but intermittent EEGs are subject to constant live interpretation. As part of quality improvement (QI), we sought to estimate the residual missed seizure rate at a typical quaternary Canadian health care center without cEEG., Methods: We calculated residual risk percentages using the clinically validated 2HELPS2B score to risk-stratify EEGs before deriving a risk percentage using a MATLAB calculator which modeled the risk decay curve for each recording. We generated a range of estimated residual seizure rates depending on whether a pre-cEEG screening EEG was simulated, EEGs showing seizures were included, or repeat EEGs on the same patient were excluded., Results: Over a 4-month QI period, 499 inpatient EEGs were scored as low (n = 125), medium (n = 123), and high (n = 251) seizure risk according to 2HELPS2B criteria. Median recording duration was 1:00:06 (interquartile range, IQR 30:40-2:21:10). The model with highest residual seizure rate included recordings with confirmed electrographic seizures (median 20.83%, IQR 20.6-26.6%), while the model with lowest residual seizure rate was in seizure-free recordings (median 10.59%, IQR 4%-20.6%). These rates were significantly higher than the benchmark 5% miss-rate threshold set by 2HELPS2B (p<0.0001)., Conclusions: We estimate that intermittent inpatient EEG misses 2-4 times more subclinical seizures than the 2HELPS2B-determined acceptable 5% seizure miss-rate threshold for cEEG. Future research is needed to determine the impact of potentially missed seizures on clinical care.

Circannual status epilepticus (SE) patterns in communities near Earth's poles best test the hypothesis that SE susceptibility varies with light exposure because these communities are routinely subject to large changes in annual light exposure, which may result in changes to daily sleep time. We compared northern hemispheric circannual SE occurrence in Kivalliq, Canada (latitude-62.8° N) to southern hemispheric Auckland, New Zealand (latitude-36.9° S). Instead of peaking at a similar calendar time, SE peaked at a similar solar time during the increasing daylight phase after each region's respective winter solstice. This demonstrates that cumulative effects of increasing light exposure can mediate SE susceptibility., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Purpose: To assess the ability of circulating tumor DNA (ctDNA)-based testing to identify patients with HER2 (encoded by ERBB2)-positive gastric/gastroesophageal adenocarcinoma (GEA) who progressed on or after trastuzumab-containing treatments were treated with combination therapy of anti-HER2 and anti-PD-1 agents., Methods: ctDNA analysis was performed retrospectively using plasma samples collected at study entry from 86 patients participating in the phase 1/2 CP-MGAH22-05 study (NCT02689284)., Results: Objective response rate (ORR) was significantly higher in evaluable ERBB2 amplification-positive vs - negative patients based on ctDNA analysis at study entry (37% vs 6%, respectively; P = .00094). ORR was 23% across all patients who were evaluable for response. ERBB2 amplification was detected at study entry in 57% of patients (all HER2 positive at diagnosis), and detection was higher (88%) when HER2 status was determined by immunohistochemistry fewer than 6 months before study entry. ctDNA was detected in 98% (84/86) of patients tested at study entry. Codetected ERBB2-activating mutations were not associated with response., Conclusions: Current ERBB2 status may be more effective than archival status at predicting clinical benefit from margetuximab plus pembrolizumab therapy. ctDNA testing for ERBB2 status prior to treatment will spare patients from repeat tissue biopsies, which may be reserved for reflex testing when ctDNA is not detected.

Background and Objectives: The validity of brain monitoring using electroencephalography (EEG), particularly to guide care in patients with acute or critical illness, requires that experts can reliably identify seizures and other potentially harmful rhythmic and periodic brain activity, collectively referred to as "ictal-interictal-injury continuum" (IIIC). Previous interrater reliability (IRR) studies are limited by small samples and selection bias. This study was conducted to assess the reliability of experts in identifying IIIC., Methods: This prospective analysis included 30 experts with subspecialty clinical neurophysiology training from 18 institutions. Experts independently scored varying numbers of ten-second EEG segments as "seizure (SZ)," "lateralized periodic discharges (LPDs)," "generalized periodic discharges (GPDs)," "lateralized rhythmic delta activity (LRDA)," "generalized rhythmic delta activity (GRDA)," or "other." EEGs were performed for clinical indications at Massachusetts General Hospital between 2006 and 2020. Primary outcome measures were pairwise IRR (average percent agreement [PA] between pairs of experts) and majority IRR (average PA with group consensus) for each class and beyond chance agreement (κ). Secondary outcomes were calibration of expert scoring to group consensus, and latent trait analysis to investigate contributions of bias and noise to scoring variability., Results: Among 2,711 EEGs, 49% were from women, and the median (IQR) age was 55 (41) years. In total, experts scored 50,697 EEG segments; the median [range] number scored by each expert was 6,287.5 [1,002, 45,267]. Overall pairwise IRR was moderate (PA 52%, κ 42%), and majority IRR was substantial (PA 65%, κ 61%). Noise-bias analysis demonstrated that a single underlying receiver operating curve can account for most variation in experts' false-positive vs true-positive characteristics (median [range] of variance explained ([Formula: see text]): 95 [93, 98]%) and for most variation in experts' precision vs sensitivity characteristics ([Formula: see text]: 75 [59, 89]%). Thus, variation between experts is mostly attributable not to differences in expertise but rather to variation in decision thresholds., Discussion: Our results provide precise estimates of expert reliability from a large and diverse sample and a parsimonious theory to explain the origin of disagreements between experts. The results also establish a standard for how well an automated IIIC classifier must perform to match experts., Classification of Evidence: This study provides Class II evidence that an independent expert review reliably identifies ictal-interictal injury continuum patterns on EEG compared with expert consensus., (© 2022 American Academy of Neurology.)

Background and Objectives: Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance. There exists a critical unmet need for an automated method to classify SZs and other SZ-like events with expert-level reliability. This study was conducted to develop and validate a computer algorithm that matches the reliability and accuracy of experts in identifying SZs and SZ-like events, known as "ictal-interictal-injury continuum" (IIIC) patterns on EEG, including SZs, lateralized and generalized periodic discharges (LPD, GPD), and lateralized and generalized rhythmic delta activity (LRDA, GRDA), and in differentiating these patterns from non-IIIC patterns., Methods: We used 6,095 scalp EEGs from 2,711 patients with and without IIIC events to train a deep neural network, SPaRCNet , to perform IIIC event classification. Independent training and test data sets were generated from 50,697 EEG segments, independently annotated by 20 fellowship-trained neurophysiologists. We assessed whether SPaRCNet performs at or above the sensitivity, specificity, precision, and calibration of fellowship-trained neurophysiologists for identifying IIIC events. Statistical performance was assessed by the calibration index and by the percentage of experts whose operating points were below the model's receiver operating characteristic curves (ROCs) and precision recall curves (PRCs) for the 6 pattern classes., Results: SPaRCNet matches or exceeds most experts in classifying IIIC events based on both calibration and discrimination metrics. For SZ, LPD, GPD, LRDA, GRDA, and "other" classes, SPaRCNet exceeds the following percentages of 20 experts-ROC: 45%, 20%, 50%, 75%, 55%, and 40%; PRC: 50%, 35%, 50%, 90%, 70%, and 45%; and calibration: 95%, 100%, 95%, 100%, 100%, and 80%, respectively., Discussion: SPaRCNet is the first algorithm to match expert performance in detecting SZs and other SZ-like events in a representative sample of EEGs. With further development, SPaRCNet may thus be a valuable tool for an expedited review of EEGs., Classification of Evidence: This study provides Class II evidence that among patients with epilepsy or critical illness undergoing EEG monitoring, SPaRCNet can differentiate (IIIC) patterns from non-IIIC events and expert neurophysiologists., (© 2023 American Academy of Neurology.)

Although not classically considered together, there is emerging evidence that Alzheimer's disease (AD) and epilepsy share a number of features and that each disease predisposes patients to developing the other. Using machine learning, we have previously developed an automated fluorodeoxyglucose positron emission tomography (FDG-PET) reading program (i.e., MAD), and demonstrated good sensitivity (84%) and specificity (95%) for differentiating AD patients versus healthy controls. In this retrospective chart review study, we investigated if epilepsy patients with/without mild cognitive symptoms also show AD-like metabolic patterns determined by the MAD algorithm. Scans from a total of 20 patients with epilepsy were included in this study. Because AD diagnoses are made late in life, only patients aged ≥40 years were considered. For the cognitively impaired patients, four of six were identified as MAD+ (i.e., the FDG-PET image is classified as AD-like by the MAD algorithm), while none of the five cognitively normal patients was identified as MAD+ (χ 2 = 8.148, p = 0.017). These results potentially suggest the usability of FDG-PET in prognosticating later dementia development in non-demented epilepsy patients, especially when combined with machine learning algorithms. A longitudinal follow-up study is warranted to assess the effectiveness of this approach.

Refractory status epilepticus (RSE) is a life-threatening emergency with high mortality and poor functional outcomes in survivors. Treatment is typically limited to intravenous anesthetic infusions and multiple anti-seizure medications. While ongoing seizures can cause permanent neurological damage, medical therapies also pose severe and life-threatening side effects. We tested the feasibility of using high-definition transcranial direct current stimulation (hd-tDCS) in the treatment of RSE. We conducted 20-min hd-tDCS sessions at an outward field orientation, intensity of 2-mA, 4 + 1 channels, and customized for deployment over the electrographic maximum of epileptiform activity ("spikes") determined by real-time clinical EEG monitoring. There were no adverse events from 32 hd-tDCS sessions in 10 RSE patients. Over steady dosing states of infusions and medications in 29 included sessions, median spike rates/patient fell by 50% during hd-tDCS on both automated (p = 0.0069) and human (p = 0.0277) spike counting. Median spike rates for any given stimulation session also fell by 50% during hd-tDCS on automated spike counting (p = 0.0032). Immediately after hd-tDCS, median spike rates/patient remained down by 25% on human spike counting (p = 0.018). Compared to historical controls, hd-tDCS subjects were successfully discharged from the intensive care unit (ICU) 45.8% more often (p = 0.004). When controls were selected using propensity score matching, the discharge rate advantage improved to 55% (p = 0.002). Customized EEG electrode targeting of hd-tDCS is a safe and non-invasive method of hyperacutely reducing epileptiform activity in RSE. Compared to historical controls, there was evidence of a cumulative chronic clinical response with more hd-tDCS subjects discharged from ICU., (© 2022. The American Society for Experimental Neurotherapeutics, Inc.)

Introduction: Interstitial lung disease (ILD) or pneumonitis remains an important adverse event identified with treatment with antibody-drug conjugates (ADCs). Drug-induced ILD (DILD) accounts for 3%-5% of common ILD cases and is a significant problem in clinical practice. Hence, with the anticipation of the widespread use of ADCs, it will be important for guidelines and recommendations to be established to direct and standardize the management of DILD by a multidisciplinary team (MDT)., Areas Covered: A thorough literature search was conducted using PubMed to identify relevant articles related to ADCs published between 1 January 2010 and 31 November 2022. Based on the review of the literature combined with expert opinions, this review article offers an overview of incidences of ILDs associated with the use of newer anticancer therapies, specifically ADCs, and discusses local-regional best practices in optimal monitoring, early diagnosis, and management of DILD involving an MDT., Expert Opinion: Multidisciplinary input and consensus are crucial in the accurate diagnosis of DILD. The core group of essential attendees in the MDT are oncologists, pulmonologists, thoracic radiologists, and pathologists. This allows for the integration of expertise from different specialists to achieve a 'best fit' diagnosis and management.

Background: Postoperative pain following pediatric cleft lip and palate repair provide unique challenges. As no guidelines presently exist, we sought to identify the most effective and safe perioperative pain management strategies for children undergoing primary cleft lip and palate repair., Methods: A systematic search of MEDLINE, Embase, Cochrane library, Scopus, and Web of Science databases was conducted. A total of 230 unique titles were then assessed. Pooled analysis of variables was conducted, and data pertaining to common approaches in decreasing postoperative analgesia were compared., Results: A total of 39 studies involving 583 and 1445 patients undergoing cleft lip and palate repair, respectively, were included. In children undergoing cleft palate repair, palatine block demonstrated the greatest latency to first analgesia (F(8,325) = 210, p<0.0001), but it was not associated with a decrease in total opioid consumption. In cleft lip, bilateral infraorbital nerve blocks resulted in the greatest increase in latency to first analgesia (215.76 min, 95% CI, 83.26 to 448.26, p<0.005) and demonstrated a mean decrease in morphine consumption of 0.2 mg/kg/d (95% CI, -0.20 to -0.20, p<0.00001). No significant intervention-related complications were identified., Conclusions: A variety of effective methods exist to decrease postoperative pain. In this review, palatine nerve block demonstrates the greatest effectiveness in palate repair, while bilateral infraorbital nerve block demonstrates an opioid-sparing effect and increased the latency to first analgesia in cleft lip repair. All studied interventions demonstrated safety in this pediatric cohort. The results of this review should be interpreted in the context of certain limitations, including the number and nature of comparison studies, and significant reporting heterogeneity., Competing Interests: Declaration of Competing Interest No conflicts to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Study Objectives: To compare estimated epileptic source localizations from 5 sleep-wake states (SWS): wakefulness (W), rapid eye movement sleep (REM), and non-REM 1-3., Methods: Electrical source localization (sLORETA) of interictal spikes from different SWS on surface EEG from the epilepsy monitoring unit at spike peak and take-off, with results mapped to individual brain models for 75% of patients. Concordance was defined as source localization voxels shared between 2 and 5 SWS, and discordance as those unique to 1 SWS against 1-4 other SWS., Results: 563 spikes from 16 prospectively recruited focal epilepsy patients across 161 day-nights. SWS exerted significant differences at spike peak but not take-off. Source localization size did not vary between SWS. REM localizations were smaller in multifocal than unifocal patients (28.8% vs. 54.4%, p = .0091). All five SWS contributed about 45% of their localizations to converge onto 17.0 ± 15.5% voxels. Against any one other SWS, REM was least concordant (54.4% vs. 66.9%, p = .0006) and most discordant (39.3% vs. 29.6%, p = .0008). REM also yielded the most unique localizations (20.0% vs. 8.6%, p = .0059)., Conclusions: REM was best suited to identify candidate epileptic sources. sLORETA proposes a model in which an "omni-concordant core" of source localizations shared by all five SWS is surrounded by a "penumbra" of source localizations shared by some but not all SWS. Uniquely, REM spares this core to "move" source voxels from the penumbra to unique cortex not localized by other SWS. This may reflect differential intra-spike propagation in REM, which may account for its reported superior localizing abilities., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Summary: As continuous brain monitoring becomes a routine part of clinical care, continuous EEG has allowed better detection and characterization of nonconvulsive seizures, and patterns along the ictal-interictal continuum in critically ill patients. However, this increased workload has led many to turn to quantitative EEG whose central tool is the "spectrogram." Although in relatively wide use, many clinicians lack a detailed understanding of how spectrograms relate to the underlying "raw" EEG signal. This article provides an approachable set of first principles to help clinicians understand how spectrograms encode information about the raw EEG and how to interpret spectrograms to efficiently infer underlying EEG patterns., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Objectives: Emerging evidence suggests that circadian rhythms affect seizure propensity in addition to, and possibly independent of, sleep-wake states. Subject to extreme seasonal changes in light and dark, the northerly Arctic can serve as a "natural experiment" to assess the real-life impact of environmental influences on seizure severity. Therefore, we evaluated the timing of seizure evacuations over 11.25 years in a well-defined region of the Canadian Arctic., Methods: Retrospective review of EEG database and patient records at the single "bottleneck" hospital to which all patients from the Kivalliq Region in Nunavut, Canada are evacuated for seizure emergencies. We calculated the mean resultant length (MRL) of circular data for circannual analysis, and conducted Rayleigh's test to assess for a statistical departure from circular uniformity., Results: Screening 40,392 EEGs, we found 117 medical evacuations from 99 distinct individuals from September 2009 to November 2020. Most evacuations occurred month-wise in May (19%); week-wise within a 7-day period in February (5%), June (5%), or November (5%); and day-wise within a 24-hour period in June (3%) or November (3%). Maximal MRL clustering occurred in April no matter if analyzed by day (0.16333, p = 0.04), week (0.16296, p = 0.04), or month (0.1736, p = 0.03)., Conclusions: A relative circannual increase in seizure evacuations between the winter and summer solstices may be related to increasing sleep loss when day length grows. Fewer evacuations between the summer and winter solstices may be related to decreased daylight and "catching up" on sleep when night length grows. Additional factors likely also play a role in circannual variation of seizure evacuations in the Arctic, which warrants further research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The World Health Organization, International League Against Epilepsy (ILAE), and International Bureau for Epilepsy have called epilepsy a public health imperative, with appropriate emphasis on low-to-middle-income countries (LMIC). Although Canada is a high-income country (HIC), income is not distributed uniformly. Furthermore, epilepsy data from the national statistical agency explicitly overlook the Arctic by excluding these territories. A common neurologic emergency, status epilepticus (SE) is a life-threatening manifestation of epilepsy that demands prompt treatment to avoid death and long-term sequelae. Therefore, we examined the rate of SE in a well-defined Canadian Arctic region., Methods: This study takes epidemiologic advantage of the Kivalliq Region's geographical isolation, which is accessible only by air. All SE patients requiring emergency care are consistently flown 1200-1900 kilometers to a single designated hospital in a distinct southern part of Canada for further management and electroencephalography (EEG). We conducted a retrospective database and chart review at this "bottleneck" hospital to identify patients with seizure(s) severe enough to justify emergency airborne medical evacuation over a 11.25-year period from 2009 to 2020., Results: We screened 40 392 EEGs to yield 117 distinct medical evacuations for "operational SE" from 99 patients to derive estimated SE incidences of 99.9 evacuations per 100 000/year and 84.5 patients per 100 000/year. The average time from seizure onset to EEG was 3.2 days. Only 16.2% of SE patients had known epilepsy. For "confirmed SE" cases meeting ILAE criteria, or cases with persistently epileptiform EEG despite days of empiric treatment, estimated incidence was 77.7 evacuations per 100 000/year and 64.9 patients per 100 000/year., Significance: High SE and epilepsy rates in the Canadian Arctic are consistent with LMIC rather than HIC. Our findings demonstrate the paradox of LMIC-equivalent epilepsy populations camouflaged within HIC. Our findings also highlight the long-standing plight of these under-served and overlooked populations hidden in plain sight., (© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: In refractory status epilepticus (RSE), the optimal degree of suppression (EEG burst suppression or merely suppressing seizures) remains unknown. Many centers lacking continuous EEG must default to serial intermittent recordings where uncertainty from lack of data may prompt more aggressive suppression. In this study, we sought to determine whether the quantitative burst suppression ratio (QBSR) from serial intermittent EEG recording is associated with RSE patient outcome., Methods: We screened the EEG database to identify non-anoxic adult RSE patients for EEG and chart review. QBSR was calculated per 10-second EEG epoch as the percentage of time during which EEG amplitude was <3 µV. Patients who survived 1-3 months after discharge from ICU and hospital comprised the favorable group. Further to initial unadjusted univariate analysis of all pooled QBSR, we conducted multivariate analyses to account for individual patient confounders ("per-capita analysis"), uneven number of EEG recordings ("per-session analysis"), and uneven number of epochs ("per-epoch analysis"). We analyzed gender, anesthetic number, and adjusted status epilepticus severity score (aSTESS) as confounders., Results: In 135,765 QBSR values over 160 EEG recordings (median 2.17 h every ≥24 h) from 17 patients on Propofol, Midazolam, and/or Ketamine, QBSR was deeper in the favorable group ( p  < 0.001) on initial unadjusted analysis. However, on adjusted multivariate analysis, there was consistently no association between QBSR and outcome. Higher aSTESS consistently associated with unfavorable outcome on per-capita (p = 0.033), per-session (p = 0.048) and per-epoch (p < 0.001) analyses. Greater maximal number of non-barbiturate anesthetic associated with favorable outcome on per-epoch analysis (p < 0.001)., Conclusions: There was no association between depth of EEG suppression using non-barbiturate anesthetic and RSE patient outcome based on QBSR from serial intermittent EEG. A per-epoch association between non-barbiturate anesthetic and favorable outcome suggests an effect from non-suppressive time-varying EEG content., Significance: Targeting and following deeper burst suppression through non-barbiturate anesthetics on serial intermittent EEG monitoring of RSE is of limited utility., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.)

Aim: The significance and prioritization of early phase oncology trial continuation during a global pandemic is unknown. This study reported the outcomes, multiple challenges, and broad recommendations associated with the impact of the novel coronavirus disease 2019 (COVID-19) on oncology early phase 1 trials-and on drug development in Asia-based on the experiences and perspectives of Asian oncology phase 1 centers., Methods: Between March and April 2020 during the initial period of outbreak, the impact of COVID-19 across oncology phase 1 sites in five Asian countries-China (Hong Kong), Japan, South Korea, Taiwan, and Singapore-was retrospectively analyzed., Results: There was no trial termination or treatment discontinuation in all five countries. Although the most common impact was new patient enrollment being placed on hold, which was based on pharmaceutical sponsors' decision-making, the situation varied per site. Most sites had no restrictions in place that would limit their ability to fully comply with the requirements of conducting the early phase studies. The number of protocol deviations during the pandemic was largely dependent on domestic transportation status during the outbreak rather than the ability of the clinical trial centers., Conclusion: Determining the risk to benefits ratio of patients with cancer who are enrolled in early phase 1 clinical trials under the unusual circumstances of a global pandemic is important. Specific guidance or guidelines on the conduct of early phase 1 clinical trials during public health emergencies that are based on the recent lessons learned is urgently required., (© 2021 The Authors. Asia-Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Objective: Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma., Methods: A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection., Results: Both NLR (median ∆+2.8 [IQR -0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3-523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02-1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01-1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39-10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21-0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01-1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01-1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55-10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21-0.80, p = 0.009) were independent prognostic factors for PFS., Conclusion: Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC., Advances in Knowledge: We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.

Despite growing use of critical care electroencephalography (ccEEG) to detect seizures and status epilepticus in the intensive care unit (ICU), integrating ccEEG findings with traditionally described benign EEG variants (BEVs) is a relatively new concept. BEV-like waveforms are now increasingly encountered in the ICU, and have also been explicitly included in proposed definitions of brief potentially ictal rhythmic discharges (BIRDs) in the ICU, bringing to the fore the question of if and which EEG patterns in critically ill patients can be safely deemed "benign". Though well-characterized as benign in healthy outpatients at low pre-test risk for neurologic disease, the significance of BEVs in the ICU remains largely unknown. Simultaneously, there has been mounting evidence to suggest that certain BEVs can arise from heterogeneous intracranial sources, including some pathologic generators. We conducted an extensive literature review on all known BEVs to assess what is known of BEVs in the ICU. Here we discuss critically ill BEVs and how to interpret them., Competing Interests: Declaration of Competing Interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Study Objectives: Rapid eye movement sleep (REM) usually suppresses interictal epileptiform discharges (IED) and seizures. However, breakthrough IEDs in REM sometimes continue. We aimed to determine if the amount of IED and seizures in REM, or REM duration, is associated with clinical trajectories., Methods: Continuous electroencephalogram (EEG) recordings from the epilepsy monitoring unit (EMU) were clipped to at least 3 h of concatenated salient findings per day including all identified REM. Concatenated EEG files were analyzed for nightly REM duration and the "REM spike burden" (RSB), defined as the proportion of REM occupied by IED or seizures. Patient charts were reviewed for clinical data, including patient-reported peak seizure frequency. Logistic and linear regressions were performed, as appropriate, to explore associations between two explanatory measures (duration of REM and RSB) and six indicators of seizure activity (clinical trajectory outcomes)., Results: The median duration of REM sleep was 43.3 (IQR 20.9-73.2) min per patient per night. 59/63 (93.7%) patients achieved REM during EMU admission. 39/59 (66.1%) patients had breakthrough IEDs or seizures in REM with the median RSB at 0.7% (IQR 0%-8.4%). Every 1% increase in RSB was associated with 1.69 (95% CI = 0.47-2.92) more seizures per month during the peak seizure period of one's epilepsy (p = 0.007)., Conclusions: Increased epileptiform activity during REM is associated with increased peak seizure frequency, suggesting an overall poorer epilepsy trajectory. Our findings suggest that RSB in the EMU is a useful biomarker to help guide about what to expect over the course of one's epilepsy., (© Sleep Research Society 2019. Published by Oxford University Press [on behalf of the Sleep Research Society]. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.

Traditional glass molding involves infrared heating; however, the thermal cycle time is long. A molding technique based on three-dimensional carbide-bonded graphene (CBG) has been developed to mold boron silicon glass. This CBG coating on a wafer silicon die can serve as a thin-film resistance heater to heat up the sample surface very rapidly with a relatively low applied voltage. To improve the precision temperature control in hot embossing so as to enhance the process quality, a heating system with lower energy consumption, shorter cycle time, and much more precision control is proposed. We have used COMSOL to simulate the whole heating process, and the heating behavior of a CBG-coated silicon wafer was experimentally investigated. The results showed that the repeatability of the heating system is stable, and it is suitable for precision glass hot embossing. Finally, an example of a precisely fabricated microlens array (Schott P-SK57) is embossed by using this novel heating system.

Monolayer graphene exhibits extraordinary properties owing to the unique, regular arrangement of atoms in it. However, graphene is usually modified for specific applications, which introduces disorder. This article presents details of graphene structure, including sp 2 hybridization, critical parameters of the unit cell, formation of σ and π bonds, electronic band structure, edge orientations, and the number and stacking order of graphene layers. We also discuss topics related to the creation and configuration of disorders in graphene, such as corrugations, topological defects, vacancies, adatoms and sp 3 -defects. The effects of these disorders on the electrical, thermal, chemical and mechanical properties of graphene are analyzed subsequently. Finally, we review previous work on the modulation of structural defects in graphene for specific applications.

Gli-similar 3 (Glis3) belongs to a Glis subfamily of Krüppel-like zinc-finger transcription factors characterized to regulate a set of downstream targets essential for cellular functions, including pancreatic development, β-cell maturation and maintenance, and insulin production. Examination of the DNA-binding domain of Glis3 reveals that this domain contains a repeated cysteine 2/histidine 2 (Cys2/His2) zinc-finger motif in the central region where the recognized DNA sequence binds. The loss of the production of pancreatic hormones, such as insulin 1 and 2, is linked to the down-regulation of β cells-related genes and promotes the apoptotic death of β cells found in mutant Glis3. Although accumulating studies converge on the Glis3 functioning in β cells, recently, there have been developments in the field of Glis3 using knockdown/mutant mice to better understand the role of Glis3 in diseases. The Glis3 mutant mice have been characterized for their propensity to develop congenital hypothyroidism, polycystic kidney disease, and some types of cancer. In this review, we attempt to comprehensively summarize the knowledge of Glis3, including its structure and general function in cells. We also collected and organized the academic achievements related to the possible mechanisms of Glis3-related diseases.

Fragile X syndrome (FXS) is a generally hereditary form of human mental retardation that is caused by triplet repeat expansion (CGG) mutation in fragile X mental retardation 1 (fmr1) gene promoter and that results in the absence of the fragile X mental retardation protein (FMRP) expression. The common symptoms of FXS patients include learning disabilities, anxiety, autistic behaviors, as well as other behavioral abnormalities. Our previous results demonstrated the behavioral abnormalities in fmr1 knockout (KO) zebrafish such as fear memory impairment and autism-like behavior. Here, we studied the functional role of fmr1 gene on the development of social behavior by behavioral experiments, including shoaling behavior, shoaling preference, light/dark test, and novel tank task. Our results demonstrated that precocious development of shoaling behavior is found in fmr1 KO zebrafish without affecting the shoaling preference on conspecific zebrafish. The shoaling behavior appeared after 14 days postfertilization (dpf), and the level of shoaling elevated in fmr1 KO zebrafish. Furthermore, the fmr1 KO zebrafish at 28 dpf expressed higher anxiety level in novel tank task. These results suggest that the change of shoaling behavior in fmr1 KO zebrafish may result from hyperactivity and an increase of anxiety.

This study was aimed to evaluate the synaptic plasticity in projections from the dorsal lateral region (Dl) to the bilateral dorsal medial region (Dm) of the zebrafish telencephalon. The results showed that unilateral electrical stimulation of the Dl evokes a negative field potential (FP) in both the contralateral and ipsilateral side of the Dm. We tested synaptic plasticity, including high-frequency stimulation-induced LTP (HFS-LTP) and low-frequency stimulation-induced LTD (LFS-LTD). We demonstrated that HFS-induced bilateral LTP is NMDAR-dependent by the application of an NMDAR antagonist, DL-AP5 (30 μM, suprafused for 10 min), which blocked the HFS-induced LTP in both the contralateral and ipsilateral Dm. In addition, LTP was restored after DL-AP5 was washed out by continuous aCSF suprafusion. These results suggested that the potentiation is NMDAR-dependent. Either LFS (1 Hz for 20 min) or applying the mGluR agonist, DHPG (40 μM, suprafused for 10 min) successfully induced bilateral LTD for at least 1 h. Furthermore, both the contralateral fEPSP and LTP vanished after ablation of the anterior commissure. In conclusion, the results of the present study suggested that the projection between the Dl and contralateral Dm in the telencephalon of zebrafish is via the anterior commissure and possesses synaptic plasticity.

Purpose: This study sought to determine the state of quantitative EEG (QEEG) use in Canada, as QEEG may provide a partial solution to the issue of escalating EEG demand against insufficient health care resources., Methods: A 10-item survey questionnaire was administered to participants at the annual meeting of the Canadian Association of Electroneurophysiology Technologists, which was held in parallel with the annual meeting of the Canadian Neurological Sciences Federation., Results: At least 70% of the Canadian population has QEEG access through academic medical institutions with applicability to adults and children. QEEG was clinically used 50% in real-time and 50% retrospectively in the critical care and epilepsy monitoring units for long-term monitoring and automated seizure detection. QEEG trend use, montage use, and duration were variable., Conclusion: To cope with insufficient health care resources, QEEG is in surprisingly frequent clinical use across Canada. There is no consensus on optimal QEEG trends and montages. The relative ubiquity of QEEG affords an excellent opportunity for research as increasing EEG demand outpaces dwindling health care resources into the foreseeable future., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Aim: To characterize patients with gastric peritoneal carcinomatosis (PC) and their typical clinical and treatment course with palliative systemic chemotherapy as the current standard of care., Methods: We performed a retrospective electronic chart review of all patients with gastric adenocarcinoma with PC diagnosed at initial metastatic presentation between January 2010 and December 2014 in a single tertiary referral centre., Results: We studied a total of 271 patients with a median age of 63.8 years and median follow-up duration of 5.1 mo. The majority ( n = 217, 80.1%) had the peritoneum as the only site of metastasis at initial presentation. Palliative systemic chemotherapy was eventually planned for 175 (64.6%) of our patients at initial presentation, of which 171 were initiated on it. Choice of first-line regime was in accordance with the National Comprehensive Cancer Network Guidelines for Gastric Cancer Treatment. These patients underwent a median of one line of chemotherapy, completing a median of six cycles in total. Chemotherapy disruption due to unplanned hospitalizations occurred in 114 (66.7%), while cessation of chemotherapy occurred in 157 (91.8%), with 42 cessations primarily attributable to PC-related complications. Patients who had initiation of systemic chemotherapy had a significantly better median overall survival than those who did not (10.9 mo vs 1.6 mo, P < 0.001). Of patients who had initiation of systemic chemotherapy, those who experienced any disruptions to chemotherapy due to unplanned hospitalizations had a significantly worse median overall survival compared to those who did not (8.7 mo vs 14.6 mo, P < 0.001)., Conclusion: Gastric PC carries a grim prognosis with a clinical course fraught with disease-related complications which may attenuate any survival benefit which palliative systemic chemotherapy may have to offer. As such, investigational use of regional therapies is warranted and required validation in patients with isolated PC to maximize their survival outcomes in the long run., Competing Interests: Conflict-of-interest statement: There are no conflict-of-interests to declare for any of the authors.