Search

The prevalence of burnout and depression among abdominal transplant surgeons has been well described. However, the incidence of early-career transplant surgeons leaving the field is unknown. The objective of this study was to quantify the incidence of attrition among early-career abdominal transplant surgeons.A custom database from the Organ Procurement and Transplantation Network with encrypted surgeon-specific identifiers was queried for transplant surgeons who entered the field between 2008 and 2019. Surgeons who experienced attrition, defined as not completing a subsequent transplant after a minimum of 5, were identified. Surgeon-specific case volumes, case mix, and recipient outcomes were modeled to describe their association with attrition.Between 2008 and 2018, 496 abdominal transplant surgeons entered the field and performed 76,465 transplant procedures. A total of 24.4% (n = 121) experienced attrition, with a median time to attrition of 2.75 years. Attrition surgeons completed fewer kidney (7 vs 21, P.01), pancreas (0.52 vs 1.43, P.01), and liver transplants (1 vs 4, P.01) in their first year of practice. Attrition surgeons completed a smaller proportion of their transplant center's volume (9% vs 18%, P.01) and were less likely to participate in pediatric transplants (26.5% vs 52.5%, P.01) and living donor kidney transplants (64.5% vs 84.5%, P.01). On multivariable analysis, performing fewer kidney (odds ratio: 0.98, 95% confidence interval: 0.98-0.99) and liver transplants (odds ratio: 0.98, 95% confidence interval: 0.97-0.98) by year 5 and completing a smaller proportion of their centers' volume (odds ratio: 0.96, 95% confidence interval: 0.94-0.98) were associated with attrition. Furthermore, attrition surgeons had worse allograft and patient survival for liver transplant recipients (both log-rank P.01).This investigation was the first to quantify the high incidence of attrition experienced by early-career abdominal transplant surgeons and its association with surgeon-specific case volumes, case mix, and worse recipient outcomes. These findings suggested the abdominal transplant workforce is struggling to retain their fellowship-trained surgeons.

Traumatic brain injury (TBI) can lead to neurocognitive decline, in part due to phosphorylated tau (p-tau). Whether p-tau accumulation worsens in the setting of polytrauma remains unknown. Propranolol has shown clinical benefit in head injuries; however, the underlying mechanism is also unknown. We hypothesize that hemorrhagic shock would worsen p-tau accumulation but that propranolol would improve functional outcomes on behavioral studies.A murine polytrauma model was developed to examine the accumulation of p-tau and whether it can be mitigated by early administration of propranolol. TBI was induced using a weight-drop model and hemorrhagic shock was achieved via controlled hemorrhage for 1 h. Mice were given intraperitoneal propranolol 4 mg/kg or saline control. The animals underwent behavioral testing at 30 d postinjury and were sacrificed for cerebral histological analysis. These studies were completed in male and female mice.TBI alone led to increased p-tau generation compared to sham on both immunohistochemistry and immunofluorescence (P 0.05). The addition of hemorrhage led to greater accumulation of p-tau in the hippocampus (P 0.007). In male mice, p-tau accumulation decreased with propranolol administration for both polytrauma and TBI alone (P 0.0001). Male mice treated with propranolol also outperformed saline-control mice on the hippocampal-dependent behavioral assessment (P = 0.0013). These results were not replicated in female mice; the addition of hemorrhage did not increase p-tau accumulation and propranolol did not demonstrate a therapeutic effect.Polytrauma including TBI generates high levels of hippocampal p-tau, but propranolol may help prevent this accumulation to improve both neuropathological and functional outcomes in males.

The authors examined how the COVID-19 pandemic affected the behavioral health of people with intellectual and developmental disabilities (IDD).A modified version of the Coronavirus Health Impact Survey-Adapted for Autism and Related Neurodevelopmental Conditions was sent to the authors' clinical networks and IDD-affiliated organizations from March to June 2021.In total, 437 people with IDD or their caregivers responded to the survey. Diagnoses included intellectual disability (51%) and autism spectrum disorder (48%). More than half (52%) of respondents reported worsened mental health. Losing access to services correlated with declining mental health. Interventions suggested to improve behavioral health included more time with friends and family (68%), more time outdoors (61%), and access to community activities (59%).COVID-19 affected the behavioral health of individuals with IDD. Survey results highlight the opportunity to leverage physical activity and pandemic-safe social supports as accessible means to mitigate gaps in services.

Striatal dopamine (DA) neurotransmission is critical for an array of reward-related behaviors and goal-directed motor control. In rodents, 95% of striatal neurons are GABAergic medium spiny neurons (MSNs) that have been traditionally segregated into two subpopulations based on the expression of stimulatory DA D1-like receptors versus inhibitory D2-like receptors. However, emerging evidence suggests that striatal cell composition is anatomically and functionally more heterogenous than previously appreciated. The presence of MSNs that co-express multiple DA receptors offers a means to more accurately understand this heterogeneity. To dissect the precise nature of MSN heterogeneity, here we used multiplex RNAscope to identify expression of three predominantly expressed DA receptors in the striatum: DA D1(D1R), D2(D2R), and D3(D3R) receptors. We report heterogenous subpopulations of MSNs that are distinctly distributed across the dorsal-ventral and rostral-caudal axes of the adult mouse striatum. These subpopulations include MSNs that co-express D1R and D2R (D1/2R), D1R and D3R (D1/3R), and D2R and D3R (D2/3R). Overall, our characterization of distinct MSN subpopulations informs our understanding of region-specific striatal cell heterogeneity.

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.

This study examined the current referral patterns and preferences of Canadian Association of Paediatric Surgeons (CAPS) and Pediatric Urologists of Canada (PUC) members for management of bladder exstrophy and cloacal anomalies (BECA).We invited CAPS and PUC members to participate in an online survey using RedCap. Demographic variables, years in practice, current referral patterns and local expertise at the participants' institution were collected. Participants' preferences towards three distinct referral models were assessed using Likert scales: no centralization of care, centralization in one or two national centres of excellence, or a consortium-based approach.There were 82 survey respondents (2/3 were CAPS members, 35.4% female, 72% in practice for10 years). Although90% of participants agreed/somewhat agreed that surgical volumes impact outcomes, 58% reported not referring out BECA patients for treatment; about 50% recognized the existence of a local dedicated expert. In terms of referral preferences, 84% of participants favoured identification of a few centres with expertise based on geographic location (a consortium-based approach), while only 7% chose a one or two national centres of excellence model. Over half of participants agreed/somewhat agreed with participating in trials of a consortium-based approach in Canada.Most CAPS and PUC members do not refer BECA patients elsewhere for treatment. Nonetheless, most surgeons recognize the importance of volume to improve outcomes and show willingness to participate in trials to concentrate experience; most participants favour a consortium-based approach through identification of a few centres of excellence based on geographic location.

OBJECTIVE: To develop an adaptive framework for seizure detection in real-time that is practical to use in the Epilepsy Monitoring Unit (EMU) as a warning signal, and whose output helps characterize epileptiform activity. METHODS: Our algorithm was tested on intracranial EEG from epilepsy patients admitted to the EMU for presurgical evaluation. Our framework uses a one-class Support Vector Machine (SVM) that is being trained dynamically according to past activity in all available channels to classify novelty of the current activity. In this study we compared multiple configurations for using a one-class SVM to assess if there is significance over specific neural features or electrode locations. RESULTS: Our results show that the algorithm reaches a sensitivity of 87% for early-onset seizure detection and of 97.7% as a generic seizure detection. CONCLUSIONS: Our algorithm is capable of running in real-time and achieving a high performance for early seizure-onset detection with a low false positive rate and robustness in detection of different type of seizure-onset patterns. SIGNIFICANCE: This algorithm offers a solution to warning systems in the EMU as well as a tool for seizure characterization during post-hoc analysis of intracranial EEG data for surgical resection of the epileptogenic network.

Despite the prevalence of opioid misuse, opioids remain the frontline treatment regimen for severe pain. However, opioid safety is hampered by side-effects such as analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, or reward. These side effects promote development of opioid use disorders and ultimately cause overdose deaths due to opioid-induced respiratory depression. The intertwined nature of signaling via μ-opioid receptors (MOR), the primary target of prescription opioids, with signaling pathways responsible for opioid side-effects presents important challenges. Therefore, a critical objective is to uncouple cellular and molecular mechanisms that selectively modulate analgesia from those that mediate side-effects. One such mechanism could be the transactivation of receptor tyrosine kinases (RTKs) via MOR. Notably, MOR-mediated side-effects can be uncoupled from analgesia signaling via targeting RTK family receptors, highlighting physiological relevance of MOR-RTKs crosstalk. This review focuses on the current state of knowledge surrounding the basic pharmacology of RTKs and bidirectional regulation of MOR signaling, as well as how MOR-RTK signaling may modulate undesirable effects of chronic opioid use, including opioid analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, and reward. Further research is needed to better understand RTK-MOR transactivation signaling pathways, and to determine if RTKs are a plausible therapeutic target for mitigating opioid side effects.

The Sentinel-2 constellation consists of two units MSI-A & MSI-B, which are Earth Observation (EO) optical missions developed and operated by the European Space Agency (ESA) in the framework of the Copernicus programme of the European Commission. The Copernicus Sentinel Optical Mission Performance Cluster (OPT-MPC) is responsible of the calibration, validation, and image quality of the user product. The inter-unit consistency of the radiometry measurements is critical for the mission as more Sentinel-2 platforms are planned in the future. In order to assess the validity and temporal stability of the radiometry measurements we use independent vicarious calibration methods for EO optical sensors, that are implemented in DIMITRI (Database for Imaging Multispectral Instruments and Tools for Radiometric Intercomparison) toolbox. The results of the validation show an excellent image quality and stable radiometric performance, which meets the mission requirements target. However, a small bias of 1.1% between the two sensors was observed in the VIS/NIR domain (see e.g. Alhammoud et al. 2021). Consequently, MSI-B measurements have been aligned with MSI-A by introducing a radiometric harmonisation factor on January 25th 2022 (PB04.00). Moreover, the OPT-MPC proposed to harmonize the sensors using MSI-A as reference for the new Collection 1 reprocessing campaign which is currently under preparation. This presentation provides a status of the Sentinel-2/MSI radiometric validation activities performed by the OPT-MPC. The results illustrate the expected improvement of the radiometric harmonisation between both units MSI-A & B. Furthermore, we present the results of cross-mission intercomparisons over desert PICS for MSI-A, MSI-B, OLI-1 and OLI- 2. The preliminary results show a good agreement between MSI/OLI to better than 2% while the OLI-1/OLI-2 agreement to better than 1% over VNIR bands. B. Alhammoud, C. Quang, V. Boccia and R. Q. Iannone, “Assessment of Copernicus Sentinel-2 Constellation After Five Years In-Orbit: Level-1C User-Products,” 2021 IEEE International Geoscience and Remote Sensing Symposium IGARSS, 2021, pp. 7759-7762, doi: 10.1109/IGARSS47720.2021.9554851

INTRODUCTION: Approximately 20–25% of human breast tumors are found within an adipose, rather than fibrous, stroma. Adipose stroma is associated with an increased risk of lymph node metastasis, but the causal association between adipose stroma and metastatic progression in human breast cancer remains unclear. METHODS: We used micropatterned type I collagen gels to engineer ~3-mm-long microscale human breast tumors within a stroma that contains adipocytes and adipose-derived stem cells (ASCs) (collectively, "adipose cells"). Invasion and escape of human breast cancer cells into an empty 120-μm-diameter lymphatic-like cavity was used to model interstitial invasion and vascular escape in the presence of adipose cell-derived factors for up to 16 days. RESULTS: We found that adipose cells hasten invasion and escape by 1–2 days and 2–3 days, respectively. These effects were mediated by soluble factors secreted by the adipose cells, and these factors acted directly on tumor cells. Surprisingly, tumor invasion and escape were more strongly induced by ASCs than by adipocytes. CONCLUSIONS: This work reveals that both adipocytes and ASCs accelerate the interstitial invasion and escape of human breast cancer cells, and sheds light on the link between adipose stroma and lymphatic metastasis in human breast cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00697-6.

Previous studies have suggested axillary lymph node dissection (ALND) can be omitted in early breast cancer patients undergoing mastectomy with positive lymph nodes (LNs). We assessed the national utilization of ALND and overall survival (OS) for larger, locally advanced tumors in patients undergoing mastectomy with positive LNs. The National Cancer Database from 2006 to 2016 was queried for mastectomy patients with clinical T3/T4, N0 tumors, and 1–2 positive LNs. Trends and outcomes for ALND were compared to sentinel lymph node biopsy (SLNB) alone. Thousand nine hundred and seventeen women were included. The proportion of ALND decreased from 70% pre-Z0011 to 52% post-Z0011. On Kaplan–Meier analysis, ALND had better OS compared to SLNB alone (p

Within Social and Personality Psychology, we have not done a good job of integrating the knowledge base of habit formation into our theoretical models, even though it is clear that habits fall within the larger domain of traits. This project reviewed the literature on the hostile attribution bias as well as habits, and found a connection between these two topics that has scarcely been explored. Both context cues and self control were found to be important for the development of bad habits as well as the presence of the hostile attribution bias. Based on the connections made, habit formation may be influential in the formation of the hostile attribution bias. Finally, a research proposal is presented to demonstrate a direction for future research to explore these two topics together.

The basal forebrain (BF) is involved in arousal, attention, and reward processing but the role of individual BF neuronal subtypes is still being uncovered. Glutamatergic neurons are the least well-understood of the three main BF neurotransmitter phenotypes. Here we analyzed the distribution, size, calcium-binding protein content and projections of the major group of BF glutamatergic neurons expressing the vesicular glutamate transporter subtype 2 (vGluT2) and tested the functional effect of activating them. Mice expressing Cre recombinase under the control of the vGluT2 promoter were crossed with a reporter strain expressing the red fluorescent protein, tdTomato, to generate vGluT2-cre-tdTomato mice. Immunohistochemical staining for choline acetyltransferase and a cross with mice expressing green fluorescent protein selectively in GABAergic neurons confirmed that cholinergic, GABAergic and vGluT2+ neurons represent distinct BF subpopulations. Subsets of BF vGluT2+ neurons expressed the calcium-binding proteins calbindin or calretinin, suggesting that multiple subtypes of BF vGluT2+ neurons exist. Anterograde tracing using adeno-associated viral vectors expressing channelrhodopsin2-enhanced yellow fluorescent fusion proteins revealed major projections of BF vGluT2+ neurons to neighboring BF cholinergic and parvalbumin neurons, as well as to extra-BF areas involved in the control of arousal or aversive/rewarding behavior such as the lateral habenula and ventral tegmental area. Optogenetic activation of BF vGluT2+ neurons elicited a striking avoidance of the area where stimulation was given, whereas stimulation of BF parvalbumin or cholinergic neurons did not. Together with previous optogenetic findings suggesting an arousal-promoting role, our findings suggest that BF vGluT2 neurons play a dual role in promoting wakefulness and avoidance behavior.

[Box: see text]

Background and ObjectivesCase reports and case series have described fluorodeoxyglucose (FDG)-PET findings in critically ill patients with rhythmic or periodic EEG patterns, with one reporting that metabolic activity increases with increasing lateralized periodic discharge (LPD) frequency. However, larger studies examining the relationship between FDG-PET hypermetabolism and rhythmic or periodic EEG patterns are lacking. The goal of this study was to investigate the association of FDG-PET hypermetabolism with electroencephalographic features in patients with neurologic disorders.MethodsThis was a single-center, retrospective study of adult patients admitted with acute neurologic symptoms who underwent FDG-PET imaging and EEG monitoring within 24 hours. Subjects were divided into 2 groups based on their FDG-PET metabolism pattern: hypermetabolic activity vs hypometabolic or normal metabolic activity. Chi-square tests and logistic regression were used to determine the relationship of FDG-PET metabolism and EEG findings.ResultsSixty patients met the inclusion criteria and underwent 63 FDG-PET studies and EEGs. Twenty-seven studies (43%) showed hypermetabolism while 36 studies (57%) showed either hypometabolism or no abnormalities on FDG-PET. Subjects with hypermetabolic FDG-PET were more likely to have electrographic seizures (44% vs 8%,p= 0.001) and LPDs with/without seizures (44% vs 14%,p= 0.007), but not other rhythmic or periodic EEG patterns (lateralized rhythmic delta activity, generalized periodic discharges, or generalized rhythmic delta activity). Subjects with hypermetabolism and LPDs were more likely to have concurrent electrographic seizures (58% vs 0%,p= 0.03), fast activity associated with the discharges (67% vs 0,p= 0.01), or spike morphology (67% vs 0,p= 0.03), compared with subjects with hypometabolic FDG-PET and LPDs.DiscussionAdults admitted with acute neurologic symptoms who had hypermetabolic FDG-PET were more likely to show electrographic seizures and LPDs, but not other rhythmic or periodic EEG patterns, compared with those with hypometabolic FDG-PET. Subjects with hypermetabolic FDG-PET and LPDs were more likely to have LPDs with concurrent electrographic seizures, LPDs with a spike morphology, and LPDs +F, compared with subjects with hypometabolic FDG-PET.

Whether formal regional lymph node (LN) evaluation is necessary for patients with appendiceal adenocarcinoma (AA) who have peritoneal metastases is unclear. The aim of this study was to evaluate the prognostic value of LN metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).A retrospective analysis of the US HIPEC collaborative, a multi-institutional consortium comprising 12 high-volume centers, was performed to identify patients with AA who underwent CRS-HIPEC with adequate LN sampling (≥ 12 LNs).Two hundred-fifty patients with AA who underwent CRS-HIPEC were included. Outcomes were compared between LN - and LN + disease. Baseline patient characteristics between groups were similar, with most patients undergoing complete cytoreduction (0/1: 86.0% vs. 76.8%, p = 0.08), respectively. More adverse tumor factors were found in patients with LN + disease, including poor differentiation, signet ring cells, and lymphovascular invasion. Multivariate analysis of overall survival (OS) found LN + disease was independently associated with worse OS (HR: 2.82 95%CI: 1.25-6.34, p = 0.01), even after correction for receipt of systemic therapy. On Kaplan-Meier analysis, median OS was lower in patients with LN + disease (25.9 months vs. 91.4 months, p 0.01). LN + disease remained associated with poor OS following propensity score matching (HR: 4.98 95%CI: 1.72-14.40, p 0.01) and in patients with PCI ≥ 20 (HR: 3.68 95%CI: 1.54-8.80, p 0.01).In this large multi-institutional study of patients with AA undergoing CRS-HIPEC, LN status remained associated with worse OS even in the setting of advanced peritoneal carcinomatosis. Formal LN evaluation should be performed for most patients with AA undergoing CRS-HIPEC.

Synthetic opioids like fentanyl are contributing to the rise in rates of opioid use disorder and drug overdose deaths. Sleep dysfunction and circadian rhythm disruption may worsen during opioid withdrawal and persist during abstinence. Severe and persistent sleep and circadian alterations are putative factors in opioid craving and relapse. However, very little is known about the impact of fentanyl on sleep architecture and sleep-wake cycles, particularly opioid withdrawal. Further, circadian rhythms regulate sleep-wake cycles, and the circadian transcription factor, neuronal PAS domain 2 (NPAS2) is involved in the modulation of sleep architecture and drug reward. Here, we investigate the role of NPAS2 in fentanyl-induced sleep alterations.To determine the effect of fentanyl administration and withdrawal on sleep architecture, and the role of NPAS2 as a factor in fentanyl-induced sleep changes.Electroencephalography (EEG) and electromyography (EMG) was used to measure non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) at baseline and following acute and chronic fentanyl administration in wild-type and NPAS2-deficient male mice.Acute and chronic administration of fentanyl led to increased wake and arousal in both wild-type and NPAS2-deficient mice, an effect that was more pronounced in NPAS2-deficient mice. Chronic fentanyl administration led to decreased NREMS, which persisted during withdrawal, progressively decreasing from day 1 to 4 of withdrawal. The impact of fentanyl on NREMS and arousal was more pronounced in NPAS2-deficient mice.Chronic fentanyl disrupts NREMS, leading to a progressive loss of NREMS during subsequent days of withdrawal. Loss of NPAS2 exacerbates the impact of fentanyl on sleep and wake, revealing a potential role for the circadian transcription factor in opioid-induced sleep changes.

RationaleSynthetic opioids like fentanyl are contributing to the rise in rates of opioid use disorder and drug overdose deaths. Sleep dysfunction and circadian rhythm disruption may worsen during opioid withdrawal and persist during abstinence. Severe and persistent sleep and circadian alterations are putative factors in opioid craving and relapse. However, very little is known about the impact of fentanyl on sleep architecture and sleep-wake cycles, particularly opioid withdrawal. Further, circadian rhythms regulate sleep-wake cycles, and the circadian transcription factor, neuronal PAS domain 2 (NPAS2) is involved in the modulation of sleep architecture and drug reward. Here, we investigate the role of NPAS2 in fentanyl-induced sleep alterations.ObjectivesTo determine the effect of fentanyl administration and withdrawal on sleep architecture, and the role of NPAS2 as a factor in fentanyl-induced sleep changes.MethodsElectroencephalography (EEG) and electromyography (EMG) was used to measure non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) at baseline and following acute and chronic fentanyl administration in wild-type and NPAS2-deficient male mice.ResultsAcute and chronic administration of fentanyl led to increased wake and arousal in both wild-type and NPAS2-deficient mice, an effect that was more pronounced in NPAS2-deficient mice. Chronic fentanyl administration led to decreased NREMS, which persisted during withdrawal, progressively decreasing from day 1 to 4 of withdrawal. The impact of fentanyl on NREMS and arousal was more pronounced in NPAS2-deficient mice.ConclusionsChronic fentanyl disrupts NREMS, leading to a progressive loss of NREMS during subsequent days of withdrawal. Loss of NPAS2 exacerbates the impact of fentanyl on sleep and wake, revealing a potential role for the circadian transcription factor in opioid-induced sleep changes.

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 ([Image: see text]): 95 [93, 98]%) and for most variation in experts' precision vs sensitivity characteristics ([Image: 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.

Ketogenic diet therapy for epilepsy has been used in adults for over 100 years. Adults with medically refractory epilepsy as well as children on diet therapies transitioning to adult care need specialty providers to support diet use. About 20% to 60% of adults report at least a 50% improvement in seizure frequency on diet therapy, and many patients report improvement in cognition and other areas as well. Diet therapy is also used in status epilepticus, with resolution of refractory status epilepticus reported in over 70% of patients. Long-term cardiovascular effects and the effects of diet therapy in pregnancy are areas of ongoing study.

Background Level 1 evidence for multimodal treatment of resectable gastric adenocarcinoma from the Intergroup 0116 (2001) and MAGIC (2006) trials demonstrated survival benefit of adjuvant chemoradiation (CRT) and perioperative chemotherapy, respectively. We evaluated the adoption of evidence-based treatment in the post-MAGIC era and its impact on survival. Methods A total of 7058 patients with resectable gastric adenocarcinoma undergoing definitive surgical resection between 2004 and 2015 were analyzed using the National Cancer Database. Results Over the study period, the proportion of patients receiving adjuvant CRT decreased from 19.1% to 9.1%, while perioperative chemotherapy increased from 1.9% to 28.6%. Utilization of perioperative chemotherapy surpassed adjuvant CRT in 2011. Evidence-based treatment (either perioperative chemotherapy or adjuvant CRT) had better overall survival (OS) than other treatments for clinical stage II–III patients (p < 0.05). On multivariate analysis of the whole study period, evidence-based treatments were associated with better OS (HR 0.67 [0.60–0.74], p < 0.05). Only 360/1262 (28.5%) patients in the perioperative chemotherapy group completed postoperative therapy, which was associated with improved OS (p < 0.05). For clinical stage III patients (n = 2402), only 806 (33.6%) received evidence-based treatment, while 487 (22.2%) underwent surgery alone. On multivariate analysis of these patients between 2010 and 2015, both perioperative chemotherapy (HR 0.49 [0.35–0.68]) and adjuvant CRT (HR 0.31 [0.21–0.44]) were associated with better OS than surgery alone (p < 0.05). Conclusions Since the INT-0116 and MAGIC trials, utilization of evidence-based treatments for resectable gastric adenocarcinoma has increased, with perioperative chemotherapy surpassing adjuvant CRT as the preferred practice. However, overall utilization of these regimens remains quite low nationally despite association with improved OS.

Packed red blood cell (pRBC) units administered during resuscitation from hemorrhagic shock are of varied storage ages. We have previously shown that RBC-derived microparticles' impact on thrombogenesis. However, the impact of storage age on pRBC coagulability is unknown. Therefore, we sought to investigate the effect of storage age on innate coagulability and aggregability of stored pRBCs.pRBCs prepared from male C57BL/6J mice were stored in Additive Solution-3 according to our standardized murine blood banking protocols for 14 days. Rotational thromboelastometry (ROTEM) was used to assess the innate coagulation status of fresh and 14-day old pRBCs. Viscoelastic coagulation parameters of clotting time (CT), clot formation time (CFT), alpha angle, and maximum clot firmness (MCF) were analyzed to determine coagulability. Plasma was added to the fresh pRBCs and 15-day old pRBCs to determine if the storage-associated coagulopathy was reversible with plasma. Statistical analyses were conducted with a Student's t-test.Fifteen-day old pRBCs demonstrated a significant reduction in MCF (10.3 vs. 24.4 mm, P-value0.001) and alpha angle (6.0 vs. 27.2 degrees, P-value0.001) as well as significant prolongation of CFT and CT (1126.5 vs. 571.4 s, P-value0.001) compared to fresh pRBCs. FFP addition to 15-day old and fresh pRBCs, demonstrated a significant reduction in MCF and persistent prolongation of CFT. This suggests that pRBCs lost coagulability as they aged and this deficit was not completely corrected by plasma administration.Storage duration may be an important factor in coagulation potential of pRBCs. Transfusion with older pRBCs may contribute to coagulopathy in massively transfused patients.

The ACOSOG Z0011 trial has essentially eliminated axillary lymph node dissection (ALND) in breast conserving therapy (BCT) patients with clinical T1/T2 and 1-2 positive sentinel lymph nodes (SLNs). Currently, ALND is recommended for positive SLNs unless ACOSOG Z0011 criteria are applicable. We aimed to assess the national trends and axillary management before and after the publication of ACOSOG Z0011 for larger tumors.An IRB-approved study evaluated the National Cancer Database from 2006 to 2016. Women with clinical T3/T4, N0 who otherwise fit ACOSOG Z0011 criteria were included. Neoadjuvant systemic therapy or known nodal disease was excluded. Clinicopathologic data were compared between two timeframes based on ACOSOZ Z0011 publication and by axillary management. Patients were categorized into SLNB alone (1-5 lymph nodes examined) and ALND (≥10 lymph nodes examined) groups.A total of 230 women fit inclusion criteria, of whom 36% underwent ALND. ALND use decreased from 54% in 2006 to 14% in 2016 (P 0.01). Comparing ALND to SLNB alone within the pre-Z0011 era, comprehensive community cancer programs had higher proportions of ALND, whereas academic centers had higher rates of SLND alone (P = 0.03). Comparing similar axillary management between eras, SLNB-alone patients in the post-Z0011 era had higher pT and pN stages, were less likely to be Her2 positive, and were more likely to receive systemic treatment.There is a national trend to forgo ALND in women who have tumors larger than those included in the Z0011 criteria without any clear clinicopathologic indications.

Noncompressible torso hemorrhage remains a leading cause of death. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) placement may occur before transport; however, its efficacy has not been demonstrated at altitude. We hypothesized that changes in altitude would not result in blood pressure changes proximal to a deployed REBOA.A simulation model for 7Fr guidewireless REBOA was used at altitudes up to 22,000 feet. Female pigs then underwent hemorrhagic shock to a mean arterial pressure (MAP) of 40 mm Hg. After hemorrhage, a REBOA catheter was deployed in the REBOA group and positioned but not inflated in the no-REBOA group. Animals underwent simulated aeromedical evacuation at 8000 ft or were left at ground level. After altitude exposure, the balloon was deflated, and the animals were observed.Taking the REBOA catheter to 22,000 ft in the simulation model resulted in a lower systolic blood pressure but a preserved MAP. In the porcine model, REBOA increased both systolic blood pressure and MAP compared with no-REBOA (P 0.05) and was unaffected by altitude. No differences in postflight blood pressure, acidosis, or systemic inflammatory response were observed between ground and altitude REBOA groups.REBOA maintained MAP up to 22,000 feet in an inanimate model. In the porcine model, REBOA deployment improved MAP, and the balloon remained effective at altitude.

Effective treatment options for patients with life-threatening neurological disorders are limited. To address this unmet need, high-impact translational research is essential for the advancement and development of novel therapeutic approaches in neurocritical care. “The Neurotherapeutics Symposium 2019—Neurological Emergencies” conference, held in Rochester, New York, in June 2019, was designed to accelerate translation of neurocritical care research via transdisciplinary team science and diversity enhancement. Diversity excellence in the neuroscience workforce brings innovative and creative perspectives, and team science broadens the scientific approach by incorporating views from multiple stakeholders. Both are essential components needed to address complex scientific questions. Under represented minorities and women were involved in the organization of the conference and accounted for 30–40% of speakers, moderators, and attendees. Participants represented a diverse group of stakeholders committed to translational research. Topics discussed at the conference included acute ischemic and hemorrhagic strokes, neurogenic respiratory dysregulation, seizures and status epilepticus, brain telemetry, neuroprognostication, disorders of consciousness, and multimodal monitoring. In these proceedings, we summarize the topics covered at the conference and suggest the groundwork for future high-yield research in neurologic emergencies.

Early detection surveillance is used for various purposes, including the early detection of non‐communicable diseases (e.g. cancer screening), of unusual increases of disease frequency (e.g. influenza or pertussis outbreaks), and the first occurrence of a disease in a previously free population. This latter purpose is particularly important due to the high consequences and cost of delayed detection of a disease moving to a new population. Quantifying the sensitivity of early detection surveillance allows important aspects of the performance of different systems, approaches and authorities to be evaluated, compared and improved. While quantitative evaluation of the sensitivity of other branches of surveillance has been available for many years, development has lagged in the area of early detection, arguably one of the most important purposes of surveillance. This paper, using mostly animal health examples, develops a simple approach to quantifying the sensitivity of early detection surveillance, in terms of population coverage, temporal coverage and detection sensitivity. This approach is extended to quantify the benefits of risk‐based approaches to early detection surveillance. Population‐based clinical surveillance (based on either farmers and their veterinarians, or patients and their local health services) provides the best combination of sensitivity, practicality and cost‐effectiveness. These systems can be significantly enhanced by removing disincentives to reporting, for instance by implementing effective strategies to improve farmer awareness and engagement with health services and addressing the challenges of well‐intentioned disease notification policies that inadvertently impose barriers to reporting.

Background Although laparoscopic sleeve gastrectomy is known, in general, to improve renal function in patients with obesity and chronic kidney disease (CKD), its effect on estimated glomerular filtration rate (eGFR) stratified by the stage of CKD is less clear. Objectives We aimed to evaluate the impact of sleeve gastrectomy on renal function in a stratified cohort of patients with CKD. Setting University Hospital. Methods We performed a retrospective review of 1932 patients who met National Institutes of Health’s guidelines for metabolic surgery and underwent laparoscopic sleeve gastrectomy performed by 1 of 3 surgeons. One hundred sixty-four patients with CKD stages 1 through 4 were identified. Results Mean follow-up period was 1.57 ± 1.0 years. Mean age was 56.4 ± 9.9 years with a preoperative body mass index of 47 ± 9 kg/m2, which decreased to 38.9 ± 8.7 kg/m2 at most recent follow-up (P Conclusion Renal function, as measured by eGFR, in patients with stages 1 and 4 CKD did not improve after laparoscopic sleeve gastrectomy; in contrast, eGFR in patients with CKD stages 2 and 3 significantly improved. Early surgical referral and intervention may be important in achieving the greatest improvement in eGFR and possibly delaying or reversing progression to end-stage renal disease.

Introduction: Intrathoracic pressure regulation (ITPR) can be utilized to enhance venous return and cardiac preload by inducing negative end expiratory pressure in mechanically ventilated patients. Previous preclinical studies have shown increased mean arterial pressure (MAP) and decreased intracranial pressure (ICP) with use of an ITPR device. The aim of this study was to evaluate the hemodynamic and respiratory effects of ITPR in a porcine polytrauma model of hemorrhagic shock and acute lung injury (ALI). Methods: Swine were anesthetized and underwent a combination of sham, hemorrhage, and/or lung injury. The experimental groups included: no injury with and without ITPR (ITPR, Sham), hemorrhage with and without ITPR (ITPR/Hem, Hem), and hemorrhage and ALI with and without ITPR (ITPR/Hem/ALI, Hem/ALI). The ITPR device was initiated at a setting of −3 cmH2O and incrementally decreased by 3 cmH2O after 30 minutes on each setting, with 15 minutes allowed for recovery between settings, to a nadir of −12 cmH2O. Histopathological analysis of the lungs was scored by blinded, independent reviewers. Of note, all animals were chemically paralyzed for the experiments to suppress gasping at ITPR pressures below −6 cmH2O. Results: Adequate shock was induced in the hemorrhage model, with the MAP being decreased in the Hem and ITPR/Hem group compared with Sham and ITPR/Sham, respectively, at all time points (Hem 54.2 ± 6.5 mmHg vs. 88.0 ± 13.9 mmHg, p

Simultaneous liver-kidney transplantation (SLKT) is indicated for patients with end-stage liver disease (ESLD) and concurrent renal insufficiency. En bloc SLKT is an alternative to traditional separate implantations, but studies comparing the two techniques are limited. The en bloc technique maintains renal outflow via donor infrahepatic vena cava and inflow via anastomosis of donor renal artery to donor splenic artery. Comparison of recipients of en bloc (n = 17) vs traditional (n = 17) SLKT between 2013 and 2017 was performed. Recipient demographics and comorbidities were similar. More recipients of traditional SLKT were dialysis dependent (82.4% vs 41.2%, P = .01) with lower baseline pretransplant eGFR (14 vs 18, P = .01). En bloc SLKT was associated with shorter kidney cold ischemia time (341 vs 533 minutes, P < .01) and operative time (374 vs 511 minutes, P < .01). Two en bloc patients underwent reoperation for kidney allograft inflow issues due to kinking and renal steal. Early kidney allograft dysfunction (23.5% in both groups), 1-year kidney graft survival (88.2% vs 82.4%, P = 1.0), and posttransplantation eGFR were similar between groups. In our experience, the en bloc SLKT technique is safe and feasible, with comparable outcomes to the traditional method.

Introduction Traumatic brain injury (TBI) has become increasingly prevalent among the injuries sustained in the military. Many wounded warriors require emergency medical evacuation via helicopter and subsequently fixed wing transport. During aeromedical evacuation, both pilots and patients experience whole body vibration due to engine, rotor, and propeller rotation. The impact of posttraumatic vibration and hypoxia exposure characteristic of the aeromedical evacuation environment on TBI is currently unknown. Methods A swine TBI model of controlled cortical impact was utilized. The pigs first underwent TBI or sham injury and were subsequently exposed to vibration or no vibration and hypoxia or normoxia for 2 hours. They were monitored for an additional 4 hours following vibration/hypoxia and blood was drawn at hourly intervals for cytokine and serum biomarker analysis. Continuous physiologic and neurologic monitoring were utilized. Prior to the conclusion of the experiment, the animals underwent brain magnetic resonance imaging. At the end of the study, the brain was extracted for histologic analysis. Results Physiologic parameters except for peripheral capillary oxygen saturation (SpO2) were similar between all groups. The hypoxia groups demonstrated the expected decrease in SpO2 and pO2 during the hypoxic period, and this was sustained throughout the study period. The pH, pCO2 and electrolytes were similar among all groups. Neuron specific enolase was increased over time in the TBI group, however it was similar to the sham TBI group at all time points. There were no differences in IL-1β, IL-6, IL-8, TNFα, GFAP, HIF1α, syndecan-1, or S100β serum levels between groups. The mean ICP during cortical impact in the TBI group was 279.8 ± 56.2 mmHg. However, the postinjury ICP was not different between groups at any subsequent time point. Brain tissue oxygenation and perfusion were similar between all groups. Conclusion In this novel study evaluating the effect of vibration on short-term outcomes following TBI, we demonstrate that the moderate vibration and hypoxia simulating aeromedical evacuation do not impact short term outcomes following TBI.

Morbid obesity serves as a barrier to kidney transplantation (KT) due to potential suboptimal posttransplant outcomes. Laparoscopic sleeve gastrectomy (LSG) has previously been shown to improve transplant eligibility through weight loss.We aimed to examine the role LSG plays in improving patient outcomes postrenal transplantation, including possible impact on new-onset diabetes after transplant (NODAT).University Hospital.A single-center analysis was performed identifying all patients who underwent KT after LSG from 2011 to 2017 (n = 41). Exclusion criteria included type I diabetes and previous pancreas transplantation. NODAT was defined as a new insulin requirement after KT. Delayed graft function was defined as need for dialysis within the first week after KT. Mean posttransplant follow-up period was 22 months.Forty-one patients underwent KT after LSG after median time of 16 months. Median age of postLSG patients undergoing KT was 56.0 years at time of KT. Average body mass index decreased by 9 from the time of LSG to KT, and no patients regained weight at 1-year follow-up. After LSG, the number of patients with hypertension (85.4% versus 48.5%) and the number of antihypertensive medications used decreased significantly (1.6 versus .6) at time of KT (P.001 each). At 1-year follow-up, the improvement in hypertension persisted (51.2% versus 48.5%, P = nonsignificant). The average insulin regimen decreased from 33.0 ± 51.6 to 11.7 ± 21.5 units at KT (P.001). This improvement also persisted at 1-year follow-up (11.9 versus 11.7 units, P = nonsignificant). Zero patients suffered NODAT over the follow-up period (versus institutional rate of NODAT at 15.8%). One patient developed delayed graft function (2.4%, versus institutional rate of 13.3%). After 1 year postKT, there was 1 graft loss (2.4%) and no mortality.This is the largest reported series of KT after planned LSG in morbidly obese patients. Our results confirm excellent posttransplant outcomes among patients who otherwise would have been denied KT eligibility.

Contains fulltext : 290882.pdf (Publisher’s version ) (Open Access) 01 februari 2023

Tetraazamacrocycles, cyclic molecules with four nitrogen atoms, have long been known to produce highly stable transition metal complexes. Cross-bridging such molecules with two-carbon chains has been shown to enhance the stability of these complexes even further. This provides enough stability to use the resulting compounds in applications as diverse and demanding as aqueous, green oxidation catalysis all the way to drug molecules injected into humans. Although the stability of these compounds is believed to result from the increased rigidity and topological complexity imparted by the cross-bridge, there is insufficient experimental data to exclude other causes. In this study, standard organic and inorganic synthetic methods were used to produce unbridged dibenzyl tetraazamacrocycle complexes of Co, Ni, Cu, and Zn that are analogues of known cross-bridged tetraazamacrocycles and their transition metal complexes to allow direct comparison of molecules that are identical except for the cross-bridge. The syntheses of the known tetraazamacrocycles and the new transition metal complexes were successful with high yields and purity. Initial chemical characterization of the complexes was conducted by UV-Visible spectroscopy, while cyclic voltammetry showed more marked differences in electronic properties from bridged versions. Direct comparison studies of the unbridged and bridged compounds’ kinetic stabilities, as demonstrated by decomposition using high acid concentration and elevated temperature, showed that the cyclen-based complex stability did not benefit from cross-bridging. This is likely due to poor complementarity with the Cu2+ ion while cyclam-based complexes benefited greatly. We conclude that ligand–metal complementarity must be maintained in order for the topological and rigidity constraints imparted by the cross-bridge to contribute significantly to complex robustness.

The Department of Surgery at the University of Cincinnati developed the Surgeons, Scholars, and Leaders Symposium to address the underappreciated aspects of surgical education that are critical in the development of the academic surgeon. Surgical education has undergone many gaps since the beginning of a traditional surgical residency, first pioneered by Dr. Halsted in 1904; still, many gaps in surgical education remain. Topics such as research, financial planning, leadership, career development, and many others are not adequately addressed in formalized training. The Surgeons, Scholars, and Leaders Symposium was first held in January 2015 in Jackson Hole, WY, and has subsequently become an annual event. Recurrent themes addressed at the Symposium include global health, resident autonomy, research program development, leadership, mentorship, career development, and managing transitions. The annual Surgeons, Scholars, and Leaders Symposium has been instrumental in addressing these underappreciated aspects of surgeon development and will continue to be an important venue for the next generation of surgical leaders.

Background Selection of patients for hyperthermic intraperitoneal chemotherapy (HIPEC) continues to evolve. We hypothesized that adjuvant HIPEC for patients at high-risk of peritoneal progression is safe and associated with favorable outcomes. Methods The institutional database of a high-volume center was queried for patients with high-risk disease undergoing HIPEC with a peritoneal carcinomatosis index (PCI) of 0. High-risk patients were defined as those with ruptured primary tumors or locally advanced (T4) disease. Results 37 patients underwent adjuvant HIPEC, with a median follow-up of 5.2 years. 54% had low-grade (LG) tumors while 46% had high-grade (HG) tumors. No patients underwent neoadjuvant chemotherapy, while eleven patients (32.4%) received adjuvant chemotherapy. There were no perioperative mortalities, and the overall complication rate was 43%. For the entire cohort, five year recurrence-free survival (RFS) and overall survival (OS) were 77% and 100%, respectively. Five year RFS and OS were 75% and 100% for LG patients and 81% and 100% for HG patients, respectively. Conclusions Adjuvant HIPEC for patients at high-risk of peritoneal progression, with PCI 0, is safe and associated with favorable long-term survival. Additional prospective investigation is needed to identify patient populations who may benefit most from HIPEC.

BACKGROUND: Several serum biomarkers have been studied to diagnose incidence and severity of traumatic brain injury (TBI), but a reliable biomarker in TBI has yet to be identified. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) has been proposed as a biomarker in clinical and preclinical studies, largely in the setting of isolated TBI or concussion. The aim of this study was to evaluate the performance of UCH-L1 as a serum biomarker in the setting of polytrauma and TBI. METHODS: Multiple variations of murine TBI and polytrauma models were used to evaluate serum biomarkers. The different models included TBI with and without hemorrhagic shock and resuscitation, isolated extremity vascular ligation, extremity ischemia/reperfusion, and blunt tail injury. Blood was drawn at intervals after injury, and serum levels of neuron-specific enolase, UCH-L1, creatine kinase, and syndecan-1 were evaluated by enzyme-linked immunosorbent assay. RESULTS: UCH-L1 levels were not significantly different between TBI, tail injury, and sham TBI. By contrast, neuron-specific enolase levels were increased in TBI mice compared with tail injury and sham TBI mice. UCH-L1 levels increased regardless of TBI status at 30 min and 4 h after hemorrhagic shock and resuscitation. In mice that underwent femoral artery cannulation followed by hemorrhagic shock/resuscitation, UCH-L1 levels were significantly elevated compared with shock sham mice at 4 h (3158 ± 2168 pg/mL, 4 h shock versus 0 ± 0 pg/mL, 4 h shock sham; P < 0.01) and at 24 h (3253 ± 2954 pg/mL, 24 h shock versus 324 ± 482 pg/mL, 24 h shock sham; P = 0.03). No differences were observed in UCH-L1 levels between the sham shock and the arterial ligation, vein ligation, or extremity ischemia/reperfusion groups at any time point. Similar to UCH-L1, creatine kinase was elevated only after shock compared with sham mice at 4, 24, and 72 h after injury. CONCLUSIONS: Our study demonstrates that UCH-L1 is not a specific marker for TBI but is elevated in models that induce central and peripheral nerve ischemia. Given the increase in UCH-L1 levels observed after hemorrhagic shock, we propose that UCH-L1 may be a useful adjunct in quantifying severity of shock or global ischemia rather than as a specific marker of TBI.

The combined injury of traumatic brain injury and hemorrhagic shock has been shown to worsen coagulopathy and systemic inflammation, thereby increasing posttraumatic morbidity and mortality. Aeromedical evacuation to definitive care may exacerbate postinjury morbidity because of the inherent hypobaric hypoxic environment. We hypothesized that blood product resuscitation may mitigate the adverse physiologic effects of postinjury flight.An established porcine model of controlled cortical injury was used to induce traumatic brain injury. Intracerebral monitors were placed to record intracranial pressure, brain tissue oxygenation, and cerebral perfusion. Each of the 42 pigs was hemorrhaged to a goal mean arterial pressure of 40 ± 5 mm Hg for 1 hour. Pigs were grouped according to resuscitation strategy used-Lactated Ringer's (LR) or shed whole blood (WB)-then placed in an altitude chamber for 2 hours at ground, 8,000 ft, or 22,000 ft, and then observed for 4 hours. Hourly blood samples were analyzed for proinflammatory cytokines and lactate. Internal jugular vein blood flow was monitored continuously for microbubble formation with altitude changes.Cerebral perfusion, tissue oxygenation, and intracranial pressure were unchanged among the six study groups. Venous microbubbles were not observed even with differing altitude or resuscitation strategy. Serum lactate levels from hour 2 of flight to the end of observation were significantly elevated in 22,000 + LR compared with 8,000 + LR and 22,000 + WB. Serum IL-6 levels were significantly elevated in 22,000 + LR compared with 22,000 + WB, 8,000 + LR and ground+LR at hour 1 of observation. Serum tumor necrosis factor-α was significantly elevated at hour 2 of flight in 8,000 + LR versus ground+LR, and in 22,000 + LR vs. 22,000 + WB at hour 1 of observation. Serum IL-1β was significantly elevated hour 1 of flight between 8,000 + LR and ground+LR.Crystalloid resuscitation during aeromedical transport may cause a prolonged lactic acidosis and proinflammatory response that can predispose multiple-injury patients to secondary cellular injury. This physiologic insult may be prevented by using blood product resuscitation strategies.

ObjectiveTo evaluate current clinical practices and evidence-based literature to establish preliminary recommendations for the management of adults using ketogenic diet therapies (KDTs).MethodsA 12-topic survey was distributed to international experts on KDTs in adults consisting of neurologists and dietitians at medical institutions providing KDTs to adults with epilepsy and other neurologic disorders. Panel survey responses were tabulated by the authors to determine the common and disparate practices between institutions and to compare these practices in adults with KDT recommendations in children and the medical literature. Recommendations are based on a combination of clinical evidence and expert opinion regarding management of KDTs.ResultsSurveys were obtained from 20 medical institutions with >2,000 adult patients treated with KDTs for epilepsy or other neurologic disorders. Common side effects reported are similar to those observed in children, and recommendations for management are comparable with important distinctions, which are emphasized. Institutions differ with regard to recommended biochemical assessment, screening, monitoring, and concern for long-term side effects, and further investigation is warranted to determine the optimal clinical management. Differences also exist between screening and monitoring practices among adult and pediatric providers.ConclusionsKDTs may be safe and effective in treating adults with drug-resistant epilepsy, and there is emerging evidence supporting the use in other adult neurologic disorders and general medical conditions as well. Therefore, expert recommendations to guide optimal care are critical as well as further evidence-based investigation.

The Radiometric Calibration Network (RadCalNet) has been established by the Committee on Earth Observation Satellites (CEOS) Working Group on Calibration and Validation (WGCV) Infrared and Visible Optical Sensors Subgroup (IVOS) in 2013 and is open to public since July 2018. The RadCalNet consists of four international test sites providing automated in situ measurements and estimates of propagated top-of-atmosphere (TOA) reflectance (Bouvet et al. 2019). This work based on the work of Alhammoud et al. (2019) for the Sentinel-2/MSI validation; and on the work of Jing et al. (2019) to correct the directional effect. In this study we extend Alhammoud et al. (2019) analysis over RadCalNet up to 2021, instead of 2018. In addition, we will present the results of a cross-mission intercomparison over RadCalNet sites for MSI-A, MSI-B and OLI-8 using DIMITRI-Toolbox. The results confirm the viewing angle effect in the Sentinel-2 data at the RVUS and LCFR sites. The correction of the directional effect improves the results over the ratios of the individual orbits by up to 5% -10%, while the average ratios has been improved by barely about 1%. However the intercomparison results illustrate the relevance of RadCalNet dataset for the vicarious validation activity. Alhammoud et al. Sentinel-2 Level-1 Radiometry Assessment Using Vicarious Methods from DIMITRI Toolbox and Field Measurements From RadCalNet Database. IEEE JSTAR, 2019, Vol: 12(9) Bouvet et al. RadCalNet: A Radiometric Calibration Network for Earth Observing Imagers Operating in the Visible to Shortwave Infrared Spectral Range. Remote Sens. 2019, 11, 2401. https://doi.org/10.3390/rs11202401 Jing et al. Evaluation of RadCalNet Output Data Using Landsat 7, Landsat 8, Sentinel 2A, and Sentinel 2B Sensors. Remote Sens. 2019, 11, 541.