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1. Autophagy and mitophagy-related extracellular mitochondrial dysfunction of cerebrospinal fluid cells in patients with hemorrhagic moyamoya disease

Author

Dong Hyuk Youn, Nayoung Kim, Aran Lee, Sung Woo Han, Jong-Tae Kim, Eun Pyo Hong, Harry Jung, Myeong Seon Jeong, Sung Min Cho, Jin Pyeong Jeon, and First Korean Stroke Genetics Association Research (The FirstKSGAR) study

Subjects
Medicine, Science
Abstract

Abstract We aimed to investigate whether mitochondrial dysfunction in extracellular cerebrospinal fluid (CSF), which is associated with autophagy and mitophagy, might be involved in neurological outcomes in adult patients with hemorrhagic moyamoya disease (MMD) whose pathogenesis related to poor outcomes is not well-known. CSF samples were collected from 43 adult MMD patients and analyzed according to outcomes at 3 months. Fluorescence-activated cell sorter analysis (FACS) and the JC-1 red/green ratio were used to assess mitochondrial cells and intact mitochondrial membrane potential (MMP). We performed quantitative real-time polymerase chain reaction and Western blotting analyses of autophagy and mitophagy-related markers, including HIF1α, ATG5, pBECN1, BECN1, BAX, BNIP3L, DAPK1, and PINK1. Finally, FACS analysis with specific fluorescence-conjugated antibodies was performed to evaluate the potential cellular origin of CSF mitochondrial cells. Twenty-seven females (62.8%) with a mean age of 47.4 ± 9.7 years were included in the study. Among 43 patients with hemorrhagic MMD, 23 (53.5%) had poor outcomes. The difference in MMP was evident between the two groups (2.4 ± 0.2 in patients with poor outcome vs. 3.5 ± 0.4 in patients with good outcome; p = 0.02). A significantly higher expression (2–ΔCt) of HIF1α, ATG5, DAPK1 followed by BAX and BNIP3L mRNA and protein was also observed in poor-outcome patients compared to those with good outcomes. Higher percentage of vWF-positive mitochondria, suggesting endothelial cell origins, was observed in patients with good outcome compared with those with poor outcome (25.0 ± 1.4% in patients with good outcome vs. 17.5 ± 1.5% in those with poor outcome; p

Published
2023
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2. Sidewall patterning of organic–inorganic multilayer thin film encapsulation by adhesion lithography

Author

Seung Woo Lee, Heyjin Cho, Choel-Min Jang, Myung-Soo Huh, and Sung Min Cho

Subjects
Medicine, Science
Abstract

Abstract A simple sidewall patterning process for organic–inorganic multilayer thin-film encapsulation (TFE) has been proposed and demonstrated. An Al2O3 thin film grown by atomic layer deposition (ALD) was patterned by adhesion lithography using the difference in interfacial adhesion strength. The difference in interfacial adhesion strength was provided by the vapor-deposited fluoro-octyl-trichloro-silane self-assembled monolayer (SAM) patterns formed by a shadow mask. The sidewall patterning of multilayer TFE was shown possible by repeating the adhesion lithography and the vapor deposition of organic polymer and SAM patterns using shadow masks. The proposed process has the advantage of being able to pattern the blanket ALD-grown Al2O3 thin films by adhesion lithography using a SAM pattern that can be more accurately predefined with a shadow mask.

Published
2023
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3. Nanocrystalline Iron Pyrophosphate-Regulated Amorphous Phosphate Overlayer for Enhancing Solar Water Oxidation

Author

Chengkai Xia, Yuankai Li, Minyeong Je, Jaekyum Kim, Sung Min Cho, Chang Hyuck Choi, Heechae Choi, Tae-Hoon Kim, and Jung Kyu Kim

Subjects
Water oxidation, Photoelectrochemical cell, Metal pyrophosphate, Electrochemical surface treatment, Technology
Abstract

Abstract A rational regulation of the solar water splitting reaction pathway by adjusting the surface composition and phase structure of catalysts is a substantial approach to ameliorate the sluggish reaction kinetics and improve the energy conversion efficiency. In this study, we demonstrate a nanocrystalline iron pyrophosphate (Fe4(P2O7)3, FePy)-regulated hybrid overlayer with amorphous iron phosphate (FePO4, FePi) on the surface of metal oxide nanostructure with boosted photoelectrochemical (PEC) water oxidation. By manipulating the facile electrochemical surface treatment followed by the phosphating process, nanocrystalline FePy is localized in the FePi amorphous overlayer to form a heterogeneous hybrid structure. The FePy-regulated hybrid overlayer (FePy@FePi) results in significantly enhanced PEC performance with long-term durability. Compared with the homogeneous FePi amorphous overlayer, FePy@FePi can improve the charge transfer efficiency more significantly, from 60% of FePi to 79% of FePy@FePi. Our density-functional theory calculations reveal that the coexistence of FePi and FePy phases on the surface of metal oxide results in much better oxygen evolution reaction kinetics, where the FePi was found to have a typical down-hill reaction for the conversion from OH* to O2, while FePy has a low free energy for the formation of OH*. Graphical abstract

Published
2022
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5. A Combined Single Trace Attack on Global Shuffling Long Integer Multiplication and its Novel Countermeasure

Author

Sangyub Lee, Sung Min Cho, Heeseok Kim, and Seokhie Hong

Subjects
Cryptography, digital signatures, elliptic curves, public key, side-channel attacks, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract

Advanced collision-based single trace attacks which can be applied on simple power analysis resistant scalar multiplications become virtual threat on elliptic curve cryptosystems recently as their practical experimental results are increasingly reported in the literature. Since such attacks are based on detecting collisions of data dependent leakage caused by underlying long integer multiplications, so-called global shuffling countermeasure which breaks such collision correlation by independently randomizing the execution order of unit operations such as single precision multiplication and carry propagation, is considered as promising countermeasure if theoretical randomness of shuffling order is guaranteed. In this paper, we firstly analyze the practical security of the global shuffling long integer multiplications by exhibiting a combined single trace attack on software implementations on an ARM Cortex-M4 microcontroller. Our combined attack consists of a simple power analysis for revealing random permutation vectors which enables later collision-based single trace attack. First we demonstrate how to reveal random permutation vectors for carry propagation process of whole global shuffling long integer multiplications within a single power trace by simple power analysis accompanied with straightforward substitution of power consumption samples. Then we perform collision-based single trace attacks after rearranging the order of subtraces for unit carry propagations based on revealed permutation vectors. Since the vulnerability to simple power analysis is originated from the if-statement for selection of proper entries of the permutation vectors, we propose a novel countermeasure which eliminates such selection with simple addition and modulus operation and also demonstrate practical result achieving regularity in power trace patterns.

Published
2020
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6. Area light source‐triggered latent angiogenic molecular mechanisms intensify therapeutic efficacy of adult stem cells

Author

Yu‐Jin Kim, Sung‐Won Kim, Gwang‐Bum Im, Yeong Hwan Kim, Gun‐Jae Jeong, Hye Ran Jeon, Dong‐Ik Kim, Haeshin Lee, Sung Young Park, Sung Min Cho, and Suk Ho Bhang

Subjects
human adipose‐derived stem cells, ischemic diseases, latent reaction period, red organic light‐emitting diode, therapeutic angiogenesis, Chemical engineering, TP155-156, Biotechnology, TP248.13-248.65, Therapeutics. Pharmacology, RM1-950
Abstract

Abstract Light‐based therapy such as photobiomodulation (PBM) reportedly produces beneficial physiological effects in cells and tissues. However, most reports have focused on the immediate and instant effects of light. Considering the physiological effects of natural light exposure in living organisms, the latent reaction period after irradiation should be deliberated. In contrast to previous reports, we examined the latent reaction period after light exposure with optimized irradiating parameters and validated novel therapeutic molecular mechanisms for the first time. we demonstrated an organic light‐emitting diode (OLED)‐based PBM (OPBM) strategy that enhances the angiogenic efficacy of human adipose‐derived stem cells (hADSCs) via direct irradiation with red OLEDs of optimized wavelength, voltage, current, luminance, and duration, and investigated the underlying molecular mechanisms. Our results revealed that the angiogenic paracrine effect, viability, and adhesion of hADSCs were significantly intensified by our OPBM strategy. Following OPBM treatment, significant changes were observed in HIF‐1α expression, intracellular reactive oxygen species levels, activation of the receptor tyrosine kinase, and glycolytic pathways in hADSCs. In addition, transplantation of OLED‐irradiated hADSCs resulted in significantly enhanced limb salvage ratio in a mouse model of hindlimb ischemia. Our OPBM might serve as a new paradigm for stem cell culture systems to develop cell‐based therapies in the future.

Published
2022
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7. Two cases of ketosis-prone diabetes mellitus in Korean adolescents

Author

Won Bin Hwang, Ji Hyun Kim, and Sung Min Cho

Subjects
ketosis-prone diabetes, child, korean, Pediatrics, RJ1-570
Abstract

In recent years, reports of diabetes mellitus (DM) cases that do not fit the traditional classification system have increased in prevalence. While insulin deficiency appears as type 1 DM (T1DM), the new type also has the clinical features of type 2 DM (T2DM); as such, this new type of DM is called ketosis-prone diabetes (KPD) and is correlated with findings of severe hyperglycemia and ketoacidosis. To provide a clear, clinical classification of DM, new classification systems are being studied. Among these, the Aβ system demonstrates the highest sensitivity and specificity in predicting clinical features and prognosis. We report 2 cases of KPD in Korean pediatric patients. The first patient was referred while in a state of diabetic ketoacidosis (DKA) and was considered to have T1DM. However, their blood glucose was well-controlled even with small doses of insulin, and the treatment was able to be changed to metformin therapy. The second patient seemed to be a typical case of T2DM because of his obesity and strong family history. However, blood glucose was not well-controlled with a regular diet, and ketosis occurred. After performing a glucagon stimulation test, both patients showed different clinical features that were finally diagnosed as type A-β+ KPD. The rapid and accurate diagnosis of KPD can reduce the duration of inappropriate insulin use and improve patients' quality of life. Further, the treatment of KPD children should be individualized according to each patient’s lifestyle to preventing recurrent DKA.

Published
2019
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8. Lightwave-reinforced stem cells with enhanced wound healing efficacy

Author

Yu-Jin Kim, Hye Ran Jeon, Sung-Won Kim, Yeong Hwan Kim, Gwang-Bum Im, Jisoo Im, Soong Ho Um, Sung Min Cho, Ju-Ro Lee, Han Young Kim, Yoon Ki Joung, Dong-Ik Kim, and Suk Ho Bhang

Subjects
Biochemistry, QD415-436
Abstract

Comprehensive research has led to significant preclinical outcomes in modified human adipose-derived mesenchymal stem cells (hADSCs). Photobiomodulation (PBM), a technique to enhance the cellular capacity of stem cells, has attracted considerable attention owing to its effectiveness and safety. Here, we suggest a red organic light-emitting diode (OLED)-based PBM strategy to augment the therapeutic efficacy of hADSCs. In vitro assessments revealed that hADSCs basked in red OLED light exhibited enhanced angiogenesis, cell adhesion, and migration compared to naïve hADSCs. We demonstrated that the enhancement of cellular capacity was due to an increased level of intracellular reactive oxygen species. Furthermore, accelerated healing and regulated inflammatory response was observed in mice transplanted with red light-basked hADSCs. Overall, our findings suggest that OLED-based PBM may be an easily accessible and attractive approach for tissue regeneration that can be applied to various clinical stem cell therapies.

Published
2021
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9. Safety of Bedside Portable Low-Field Brain MRI in ECMO Patients Supported on Intra-Aortic Balloon Pump

Author

Christopher Wilcox, Matthew Acton, Hannah Rando, Steven Keller, Haris I. Sair, Ifeanyi Chinedozi, John Pitts, Bo Soo Kim, Glenn Whitman, and Sung Min Cho

Subjects
portable MRI, ECMO, VA ECMO, IABP, safety, brain injury, Medicine (General), R5-920
Abstract

(1) Background: Fifty percent of patients supported on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are concurrently supported with an intra-aortic balloon pump (IABP). Acute brain injury (ABI) is a devastating complication related to ECMO and IABP use. The standard of care for ABI diagnosis requires transport to a head CT (HCT) scanner. Recent data suggest that point-of-care (POC) magnetic resonance imaging (MRI) is safe and may be effective in diagnosing ABI in ECMO patients; however, no data exist in patients supported on ECMO with an IABP. We report pre-clinical safety data and a case series to evaluate the safety and feasibility of POC brain MRI in ECMO patients supported with IABP. (2) Methods: Prior to patient use, ex vivo testing with an IABP catheter within the Swoop® Portable MRI (0.064 T) System™ was conducted. After IRB approval, clinical testing was performed for the safety and feasibility of early ABI detection. (3) Results: No deflection force was measured with a 7.5 French Maquet Linear IABP within the 0.064 T field. Three adult ECMO patients (average age: 40 years; 67% female) supported with IABP completed four POC brain MRI exams (median exam time: 30 min). Multiple signal abnormalities were detected on the POC brain MRI, corresponding to HCT results. (4) Conclusions: Our preliminary results suggest that adult VA-ECMO patients with IABP support can be safely imaged with low-field POC brain MRI in the intensive care unit, allowing for the early and bedside imaging of patients.

Published
2022
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10. Novel Key Recovery Attack on Secure ECDSA Implementation by Exploiting Collisions between Unknown Entries

Author

Sunghyun Jin, Sangyub Lee, Sung Min Cho, HeeSeok Kim, and Seokhie Hong

Subjects
Public-key cryptography, Digital signature, ECDSA, Scalar multiplication, Side-channel analysis, Collision attack, Computer engineering. Computer hardware, TK7885-7895, Information technology, T58.5-58.64
Abstract

In this paper, we propose a novel key recovery attack against secure ECDSA signature generation employing regular table-based scalar multiplication. Our attack exploits novel leakage, denoted by collision information, which can be constructed by iteratively determining whether two entries loaded from the table are the same or not through side-channel collision analysis. Without knowing the actual value of the table entries, an adversary can recover the private key of ECDSA by finding the condition for which several nonces are linearly dependent by exploiting only the collision information. We show that this condition can be satisfied practically with a reasonable number of digital signatures and corresponding traces. Furthermore, we also show that all entries in the pre-computation table can be recovered using the recovered private key and a sufficient number of digital signatures based on the collision information. As case studies, we find that fixed-base comb and T_SM scalar multiplication are vulnerable to our attack. Finally, we verify that our attack is a real threat by conducting an experiment with power consumption traces acquired during T_SM scalar multiplication operations on an ARM Cortex-M based microcontroller. We also provide the details for validation process.

Published
2021
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11. A Practical Collision-Based Power Analysis on RSA Prime Generation and Its Countermeasure

Author

Sangyub Lee, Sung Min Cho, Heeseok Kim, and Seokhie Hong

Subjects
Cryptography, digital signatures, public key, side-channel attacks, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract

We analyze the security of RSA prime generation implemented on embedded devices by a practical power analysis attack. Unlike previous differential power analysis-based attack on primality tests of RSA prime generation exploiting the deterministic relationship among multiple prime candidates manipulated by consecutive primality tests, we propose a collision-based power analysis attack on the Miller-Rabin test for a single prime candidate which can recover the secret prime with a single attempt by exploiting collision characteristics of simple power analysis resistant modular exponentiation algorithms. Hence, our attack does not require the incremental prime search assumption and is applicable when countermeasures against previous attacks are deployed since it also does not require the assumption of trial divisions with small primes on prime candidates. For a realistic setting, where five 512-bit modular exponentiations are operated on an ARM Cortex-M4 microcontroller as recommended by FIPS 186-4 standard, we successfully recover the secret exponent to an extent that a feasible exhaustive search is needed for the full recovery of the secret prime. This is a first practical result of recovering a full secret of modular exponentiation which manipulates 512-bit RSA primitives with collision-based power analysis in a single attempt, where the previous attack demonstrates the result for 192-bit ECC primitive implementations. We also present a countermeasure against our attack which requires only one additional modular subtraction for the loop of square-and-multiply-always exponentiation algorithm. An experimental result for the effectiveness of our proposed countermeasure is presented.

Published
2019
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13. A compound heterozygous mutation in the gene: the first pediatric case causes fish odor syndrome in Korea

Author

Ji Hyun Kim, Sung Min Cho, and Jong-Hee Chae

Subjects
Trimethylaminuria, Fish odor syndrome, FMO3, Mutation, Pediatrics, RJ1-570
Abstract

Trimethylaminuria (TMAuria), known as “fish odor syndrome,” is a congenital metabolic disorder characterized by an odor resembling that of rotting fish. This odor is caused by the secretion of trimethylamine (TMA) in the breath, sweat, and body secretions and the excretion of TMA along with urine. TMAuria is an autosomal recessive disorder caused by mutations in flavin-containing monooxygenase 3 (FMO3). Most TMAuria cases are caused by missense mutations, but nonsense mutations have also been reported in these cases. Here, we describe the identification of a novel FMO3 gene mutation in a patient with TMAuria and her family. A 3-year-old girl presented with a strong corporal odor after ingesting fish. Genomic DNA sequence analysis revealed that she had compound heterozygous FMO3 mutations; One mutation was the missense mutation p.Val158Ile in exon 3, and the other was a novel nonsense mutation, p.Ser364X, in exon 7 of the FMO3 gene. Familial genetic analyses showed that the p.Val158Ile mutation was derived from the same allele in the father, and the p.Ser364X mutation was derived from the mother. This is the first description of the p.Ser364X mutation, and the first report of a Korean patient with TMAuria caused by novel compound heterozygous mutations.

Published
2017
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14. Identification and Validation of VEGFR2 Kinase as a Target of Voacangine by a Systematic Combination of DARTS and MSI

Author

Yonghyo Kim, Yutaka Sugihara, Tae Young Kim, Sung Min Cho, Jin Young Kim, Ju Yeon Lee, Jong Shin Yoo, Doona Song, Gyoonhee Han, Melinda Rezeli, Charlotte Welinder, Roger Appelqvist, György Marko-Varga, and Ho Jeong Kwon

Subjects
target identification, target validation, label-free method for drugs, anti-angiogenesis, mechanism of action, receptor tyrosine kinases, Microbiology, QR1-502
Abstract

Although natural products are an important source of drugs and drug leads, identification and validation of their target proteins have proven difficult. Here, we report the development of a systematic strategy for target identification and validation employing drug affinity responsive target stability (DARTS) and mass spectrometry imaging (MSI) without modifying or labeling natural compounds. Through a validation step using curcumin, which targets aminopeptidase N (APN), we successfully standardized the systematic strategy. Using label-free voacangine, an antiangiogenic alkaloid molecule as the model natural compound, DARTS analysis revealed vascular endothelial growth factor receptor 2 (VEGFR2) as a target protein. Voacangine inhibits VEGFR2 kinase activity and its downstream signaling by binding to the kinase domain of VEGFR2, as was revealed by docking simulation. Through cell culture assays, voacangine was found to inhibit the growth of glioblastoma cells expressing high levels of VEGFR2. Specific localization of voacangine to tumor compartments in a glioblastoma xenograft mouse was revealed by MSI analysis. The overlap of histological images with the MSI signals for voacangine was intense in the tumor regions and showed colocalization of voacangine and VEGFR2 in the tumor tissues by immunofluorescence analysis of VEGFR2. The strategy employing DARTS and MSI to identify and validate the targets of a natural compound as demonstrated for voacangine in this study is expected to streamline the general approach of drug discovery and validation using other biomolecules including natural products.

Published
2020
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15. Electrical and optical analyses of tandem organic light-emitting diodes with organic charge-generation layer

Author

Bong Sung Kim, Heeyeop Chae, Ho Kyoon Chung, and Sung Min Cho

Subjects
Physics, QC1-999
Abstract

The electrical and optical properties of tandem organic light-emitting diodes (OLEDs), in which a fluorescent and phosphorescent emitting units are connected by an organic charge-generation layer (CGL), were experimentally analyzed. To investigate the internal properties of the tandem OLEDs, we fabricated and compared two single, two homo-tandem, and two hetero-tandem OLEDs using the fluorescent and phosphorescent units. From the experimental results of the OLEDs obtained at the same current density, the voltage across the CGL as well as the individual emission spectra and luminance of each unit of tandem OLEDs were obtained and compared with the theoretical simulation results. The analysis method proposed in this study can be utilized as a method to verify the accuracy of optical or electrical computer simulation of tandem OLED and it will be useful to understand the overall electrical and optical characteristics of tandem OLEDs.

Published
2018
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16. Clinical risk factors for Clostridium difficile-associated diseases

Author

Sung Min Cho, Jae Joon Lee, and Hee Jung Yoon

Subjects
Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

Many factors appear to influence the chance of acquiring Clostridium difficile (C. difficile) infection, and an accurate identification of risk factors could be beneficial in many ways. Thus, in the present study, clinical risk factors for C. difficile-associated disease (CDAD) in Korea were identified. A total of 93 patients who met the inclusion criteria and 186 age/gender/ward/admission period-matched control patients were included in this study. Statistically significant associations were found with presence of chronic lung diseases (odds ratio [OR], 3.41; 95% confidence interval [CI], 1.25–9.32; p = 0.017), presence of ileus (OR, 10.05; 95% CI, 2.42–41.80; p = 0.001), presence of intensive care unit (ICU) stay (OR, 9.79; 95% CI, 3.03–31.68; p

Published
2012
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17. Side-Channel Vulnerabilities of Unified Point Addition on Binary Huff Curve and Its Countermeasure

Author

Sung Min Cho, Sunghyun Jin, and HeeSeok Kim

Subjects
unified point addition, binary Huff curve, recovery of secret exponent by triangular trace analysis, horizontal collision correlation analysis, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

Unified point addition for computing elliptic curve point addition and doubling is considered to be resistant to simple power analysis. Recently, new side-channel attacks, such as recovery of secret exponent by triangular trace analysis and horizontal collision correlation analysis, have been successfully applied to elliptic curve methods to investigate their resistance to side-channel attacks. These attacks turn out to be very powerful since they only require leakage of a single power consumption trace. In this paper, using these side-channel attack analyses, we introduce two vulnerabilities of unified point addition on the binary Huff curve. Also, we propose a new unified point addition method for the binary Huff curve. Furthermore, to secure against these vulnerabilities, we apply an equivalence class to the side-channel atomic algorithm using the proposed unified point addition method.

Published
2018
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18. Cross-Linked Poly(vinylidene fluoride-co-hexafluoropropene) (PVDF-co-HFP) Gel Polymer Electrolyte for Flexible Li-Ion Battery Integrated with Organic Light Emitting Diode (OLED)

Author

Ilhwan Kim, Bong Sung Kim, Seunghoon Nam, Hoo-Jeong Lee, Ho Kyoon Chung, Sung Min Cho, Thi Hoai Thuong Luu, Seungmin Hyun, and Chiwon Kang

Subjects
cross-linked poly(vinylidene fluoride-co-hexafluoropropene) (PVDF-co-HFP), gel polymer electrolyte (GPE), electrospinning, N-methyl-2-pyrrolidone (NMP), ionic conductivity, flexible Li-ion batteries, organic light emitting diode (OLED), Technology, Electrical engineering. Electronics. Nuclear engineering, TK1-9971, Engineering (General). Civil engineering (General), TA1-2040, Microscopy, QH201-278.5, Descriptive and experimental mechanics, QC120-168.85
Abstract

Here, we fabricate poly(vinylidene fluoride-co-hexafluoropropene) (PVDF-co-HFP) by electrospinning for a gel polymer electrolyte (GPE) for use in flexible Li-ion batteries (LIBs). As a solvent, we use N-methyl-2-pyrrolidone (NMP), which helps produce the cross-linked morphology of PVDF-co-HFP separator, owing to its low volatility. The cross-linked PVDF-co-HFP separator shows an uptake rate higher than that of a commercialized polypropylene (PP) separator. Moreover, the PVDF-co-HFP separator shows an ionic conductivity of 2.3 × 10−3 S/cm at room temperature, comparable with previously reported values. An LIB full-cell assembled with the PVDF-co-HFP-based GPE shows capacities higher than its counterpart with the commercialized PP separator, confirming that the cross-linked PVDF-co-HFP separator provides highly efficient ionic conducting pathways. In addition, we integrate a flexible LIB cell using the PVDF-co-HFP GPE with a flexible organic light emitting diode (OLED), demonstrating a fully flexible unit of LIB and OLED.

Published
2018
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19. Simultaneous Determination of Multi-Mycotoxins in Cereal Grains Collected from South Korea by LC/MS/MS

Author

Dong-Ho Kim, Sung-Yong Hong, Jea Woo Kang, Sung Min Cho, Kyu Ri Lee, Tae Kyung An, Chan Lee, and Soo Hyun Chung

Subjects
aflatoxins, deoxynivalenol, fumonisins, HT-2, nivalenol, ochratoxin A, T-2, zearalenone, grains, LC/MS/MS, Medicine
Abstract

An improved analytical method compared with conventional ones was developed for simultaneous determination of 13 mycotoxins (deoxynivalenol, nivalenol, 3-acetylnivalenol, aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2, fumonisin B1, fumonisin B2, T-2, HT-2, zearalenone, and ochratoxin A) in cereal grains by liquid chromatography-tandem mass spectrometry (LC/MS/MS) after a single immunoaffinity column clean-up. The method showed a good linearity, sensitivity, specificity, and accuracy in mycotoxin determination by LC/MS/MS. The levels of 13 mycotoxins in 5 types of commercial grains (brown rice, maize, millet, sorghum, and mixed cereal) from South Korea were determined in a total of 507 cereal grains. Mycotoxins produced from Fusarium sp. (fumonisins, deoxynivalenol, nivalenol, and zearalenone) were more frequently (more than 5%) and concurrently detected in all cereal grains along with higher mean levels (4.3–161.0 ng/g) in positive samples than other toxins such as aflatoxins and ochratoxin A (less than 9% and below 5.2 ng/g in positive samples) from other fungal species.

Published
2017
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20. Endogenous orexin and hyperacute autonomic responses after resuscitation in a preclinical model of cardiac arrest.

Author

Yu Guo, Gharibani, Payam, Agarwal, Prachi, Modi, Hiren, Sung-Min Cho, Thakor, Nitish V., and Geocadin, Romergryko G.

Subjects
LABORATORY rats, SYSTOLIC blood pressure, CARDIAC arrest, CEREBRAL ischemia, BLOOD pressure
Abstract

Objectives: The study of autonomic responses to cardiac arrest (CA) resuscitation deserves attention due to the impact of autonomic function on survival and arousal. Orexins are known to modulate autonomic function, but the role of endogenous orexin in hyperacute recovery of autonomic function postresuscitation is not well understood. We hypothesized that endogenous orexin facilitates hyperacute cardiovascular sympathetic activity post-resuscitation, and this response could be attenuated by suvorexant, a dual orexin receptor antagonist. Methods: A well-established 7-min asphyxial CA rat model was studied. Heart rate (HR) and blood pressure were monitored from baseline to 90-min postresuscitation. Autonomic function was evaluated by spectral analysis of HR variability, whereby the ratio of low- and high-frequency components (LF/HF ratio) represents the balance between sympathetic/parasympathetic activities. Plasma orexin-A levels and orexin receptors immunoreactivity in the rostral ventrolateral medulla (RVLM), the key central region for regulating sympathetic output, were measured post-resuscitation. Neurological outcome was assessed via neurologic-deficit score at 4-h post-resuscitation. Key results: A significant increase in HR was found over 25-40 min postresuscitation (p < 0.01 vs. baseline), which was attenuated by suvorexant significantly (p < 0.05). Increased HR (from 15-to 25-min post-resuscitation) was correlated with better neurological outcomes (rs = 0.827, p = 0.005). There was no evident increase in mean arterial pressure over 25-40 min post-resuscitation, while systolic pressure was reduced greatly by suvorexant (p < 0.05). The LF/HF ratio was higher in animals with favorable outcomes than in animals injected with suvorexant over 30-40 min post-resuscitation (p < 0.05). Plasma orexin-A levels elevated at 15-min and peaked at 30-min post-resuscitation (p < 0.01 vs. baseline). Activated orexin receptors-immunoreactive neurons were found co-stained with tyrosine hydroxylase-immunopositive cells in the RVLM at 2-h post-resuscitation. Conclusion: Together, increased HR and elevated LF/HF ratio indicative of sympathetic arousal during a critical window (25-40 min) post-resuscitation are observed in animals with favorable outcomes. The orexin system appears to facilitate this hyperacute autonomic response post-CA. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Clinical risk factors for Clostridium difficile-associated diseases

Author

Sung Min Cho, Jae Joon Lee, and Hee Jung Yoon

Subjects
risk factors, Clostridium difficile-associated, diseases, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

Many factors appear to influence the chance of acquiring Clostridium difficile (C. difficile) infection, and an accurate identification of risk factors could be beneficial in many ways. Thus, in the present study, clinical risk factors for C. difficile-associated disease (CDAD) in Korea were identified. A total of 93 patients who met the inclusion criteria and 186 age/gender/ward/admission period-matched control patients were included in this study. Statistically significant associations were found with presence of chronic lung diseases (odds ratio [OR], 3.41; 95% confidence interval [CI], 1.25-9.32; p = 0.017), presence of ileus (OR, 10.05; 95% CI, 2.42-41.80; p = 0.001), presence of intensive care unit (ICU) stay (OR, 9.79; 95% CI, 3.03-31.68; p < 0.001), use of cephalosphorins (OR, 3.30; 95% CI, 1.13-9.62; p = 0.029), history of surgery (OR, 10.89; 95% CI, 3.96-29.92; p < 0.001), and history of long-term care facility stay (OR, 14.90; 95% CI, 4.02-55.26; p < 0.001). Awareness of CDAD is critical to provide appropriate clinical care. Surveillance of the national incidence rate and multicenter studies are needed, and the potential value of a C. difficile vaccine should be studied.

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23. Arterial oxygen and carbon dioxide tension and acute brain injury in extracorporeal cardiopulmonary resuscitation patients: Analysis of the extracorporeal life support organization registry

Author

Benjamin L Shou, Chin Siang Ong, Lavienraj Premraj, Patricia Brown, Joseph E. Tonna, Heidi J Dalton, Bo Soo Kim, Steven P Keller, Glenn JR Whitman, and Sung-Min Cho

Subjects
Pulmonary and Respiratory Medicine, Transplantation, Surgery, Cardiology and Cardiovascular Medicine, Article
Abstract

ObjectiveAcute brain injury remains common after extracorporeal cardiopulmonary resuscitation. Using a large international multicenter cohort, we investigated the impact of peri-cannulation arterial oxygen (PaO2) and carbon dioxide (PaCO2) on ABI occurrence.DesignRetrospective cohort study.SettingData in the Extracorporeal Life Support Organization Registry from 2009 to 2020.PatientsAdult patients (≥18 years old) who underwent extracorporeal cardiopulmonary resuscitation.InterventionsNone.Measurements and Main ResultsOf 3,125 patients with extracorporeal cardiopulmonary resuscitation (median age=58, 69% male), 488 (16%) experienced at least one form of acute brain injury, which included ischemic stroke, intracranial hemorrhage, seizures, and brain death. 217 (7%) experienced ischemic stroke and 88 (3%) experienced intracranial hemorrhage. The registry collects two blood gas data pre- (6 hours before) and on- (24 hours after) extracorporeal membrane oxygenation (ECMO) cannulation. Blood gas parameters were classified as: hypoxia (2 levels were not significantly associated with composite ABI or mortality, though mild hypercarbia pre- and on-ECMO were protective of ischemic stroke and intracranial hemorrhage, respectively.ConclusionsEarly severe hyperoxia (≥300mmHg) on ECMO was a significant risk factor for acute brain injury and mortality for patients undergoing extracorporeal cardiopulmonary resuscitation. Careful consideration should be given in early oxygen delivery in ECPR patients who are at risk of reperfusion injury.

Published
2023

24. Management of Anticoagulation Therapy in ECMO-Associated Ischemic Stroke and Intracranial Hemorrhage

Author

Rochelle Prokupets, Nivedha Kannapadi, Henry Chang, Giorgio Caturegli, Errol L. Bush, Bo Soo Kim, Steven Keller, Romergryko G. Geocadin, Glenn J. R. Whitman, Sung-Min Cho, Matthew Acton, Hannah Rando, Diane Alejo, Kate Calligy, Scott Anderson, Benjamin Shou, Marc Sussman, Christopher Wilcox, Lucy Zhang, Patricia Brown, and Anna Peeler

Subjects
Pulmonary and Respiratory Medicine, Surgery, General Medicine, Cardiology and Cardiovascular Medicine, Article
Abstract

Objective: Despite the common occurrence of extracorporeal membrane oxygenation (ECMO)–associated acute ischemic stroke (AIS) and intracranial hemorrhage (ICH), there are little data to guide optimal anticoagulation management. We sought to describe antithrombotic therapy management after stroke and outcomes. Methods: A retrospective analysis was conducted of venoarterial (VA) and venovenous (VV) ECMO patients treated at a tertiary care center from June 2016 to February 2021. Patients with image-confirmed diagnosis of AIS or ICH while receiving ECMO were included for study with data collected regarding anticoagulation management and clinical outcomes. Results: Overall, 216 patients (153 VA-ECMO, 63 VV-ECMO) were included in this study. Of the 153 patients on VA-ECMO, 13 (8.4%) had AIS and 6 (3.9%) had ICH. Of the 63 patients on VV-ECMO, none had AIS and 5 (7.9%) had ICH. One patient (9%) received anticoagulation reversal after ICH. Anticoagulation was discontinued and later resumed in all 5 ICH survivors (median cessation time, 30 h) and 1 of 2 (50%) AIS survivors (median cessation time, 96 h). While off anticoagulation, 2 of 11 patients (18%) had thromboembolic events and none had new AIS. Upon resumption, there were no cases of hemorrhagic transformation of AIS or ICH expansion. There was no difference in in-hospital mortality between patients with ICH and those without in both the VA-ECMO and VV-ECMO cohorts nor between VA-ECMO patients with AIS and those without. Conclusions: Early cessation and judicious resumption of anticoagulation appeared feasible in the cohort of patients with ECMO-associated AIS and ICH.

Published
2023

25. Tracheostomy outcomes in critically ill patients with COVID-19: a systematic review, meta-analysis, and meta-regression

Author

Denise Battaglini, Lavienraj Premraj, Nicole White, Anna-Liisa Sutt, Chiara Robba, Sung-Min Cho, Ida Di Giacinto, Filippo Bressan, Massimiliano Sorbello, Brian H. Cuthbertson, Gianluigi Li Bassi, Jacky Suen, John F. Fraser, and Paolo Pelosi

Subjects
Time Factors, Tracheostomy, Anesthesiology and Pain Medicine, Critical Illness, Humans, COVID-19, Length of Stay, Respiration, Artificial
Abstract

We performed a systematic review of mechanically ventilated patients with COVID-19, which analysed the effect of tracheostomy timing and technique (surgical vs percutaneous) on mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS), decannulation from tracheostomy, duration of mechanical ventilation, and complications.Four databases were screened between January 1, 2020 and January 10, 2022 (PubMed, Embase, Scopus, and Cochrane). Papers were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Population or Problem, Intervention or exposure, Comparison, and Outcome (PICO) guidelines. Meta-analysis and meta-regression for main outcomes were performed.The search yielded 9024 potentially relevant studies, of which 47 (n=5268 patients) were included. High levels of between-study heterogeneity were observed across study outcomes. The pooled mean tracheostomy timing was 16.5 days (95% confidence interval [CI]: 14.7-18.4; IIn patients with COVID-19 requiring tracheostomy, the timing and technique of tracheostomy did not clearly impact on patient outcomes.PROSPERO CRD42021272220.

Published
2022

26. Transcranial Doppler microemboli and acute brain injury in extracorporeal membrane oxygenation: A prospective observational study

Author

Giorgio Caturegli, Shrey Kapoor, Vladimir Ponomarev, Bo Soo Kim, Glenn J.R. Whitman, Wendy Ziai, Sung-Min Cho, Lucy Q. Zhang, Yunis Mayasi, Aaron Gusdon, Bahattin Ergin, Steven Keller, Matthew Acton, Hannah Rando, Diane Alejo, Kate Calligy, Scott Anderson, Benjamin Shou, Pedro A. Mendez-Tellez, Henry Chang, Marc Sussman, Christopher Wilcox, Patricia Brown, and Anna Peeler

Subjects
Pulmonary and Respiratory Medicine, Surgery
Abstract

Extracorporeal membrane oxygenation (ECMO) carries a high morbidity of acute brain injury (ABI) with resultant mortality increase. Transcranial Doppler (TCD) allows real-time characterization of regional cerebral hemodynamics, but limited data exist on the interpretation of microembolic signals (MES) in ECMO.This prospective cohort study was conducted at a single tertiary care center, November 2017 through February 2022, and included all adult patients receiving venoarterial (VA) and venovenous (VV) ECMO undergoing TCD examinations, which all included MES monitoring.Of 145 patients on ECMO who underwent at least 1 TCD examination, 100 (68.9%) patients on VA-ECMO received 187 examinations whereas 45 (31.1%) patients on VV-ECMO received 65 examinations (TCD analysis in a large cohort of patients on ECMO demonstrates a significant number of MES, especially in patients on VA-ECMO with intra-aortic balloon pump, and/or left ventricular assist device. However, clinical associations and significance of TCD MES remain unresolved and warrant further correlation with systematic imaging and long-term neurologic follow-up.

Published
2022

27. Recent applications of quantitative electroencephalography in adult intensive care units: a comprehensive review

Author

Jaeho Hwang, Sung-Min Cho, and Eva K. Ritzl

Subjects
Adult, Intensive Care Units, Neurology, Humans, Electroencephalography, Neurology (clinical), Child, Algorithms, Article
Abstract

Quantitative electroencephalography (qEEG) refers to the numerical analysis and/or visual transformations of raw electroencephalography (EEG) signals. Evaluation of qEEG in intensive care units (ICU) faces unique challenges that warrant investigation separate from those conducted in other settings. Additionally, the pathophysiology, management, and EEG patterns of critically ill conditions often significantly differ between adults and children. Thus, it is important to distinguish the literature on qEEGs specifically performed in adult ICUs. The aim of this review is to summarize the studies using qEEG for clinical evaluation of patients in adult ICUs performed over the past decade (since 2010), and to present the state of the art of these techniques. Overall, these studies have reported that qEEG can reveal important information faster than typically possible with traditional methods of reviewing the raw EEG only, with reasonable accuracy. However, it is crucial to emphasize that qEEG must be reviewed in conjunction with raw EEG and in context of understanding the patients' clinical status. Because each qEEG panel only focuses on a few aspects of the entire EEG, different combinations of qEEG panels may be required for optimal analyses of each medical condition and individual patient. Currently in practical terms, qEEG can serve as a complementary, valuable tool for portions of the EEG that require more detailed review. Further multi-center collaborative studies are needed to ultimately develop standardized methods of employing qEEG that are generalizable across institutions. As qEEG techniques continue to advance, including those involving machine learning, qEEG will further benefit from algorithms specifically suited for ICUs.

Published
2022

28. Hypoxic-Ischemic Brain Injury in ECMO: Pathophysiology, Neuromonitoring, and Therapeutic Opportunities

Author

Shivalika Khanduja, Jiah Kim, Jin Kook Kang, Cheng-Yuan Feng, Melissa Ann Vogelsong, Romergryko G Geocadin, Glenn Whitman, and Sung-Min Cho

Abstract

Extracorporeal membrane oxygenation (ECMO), in conjunction with its life-saving benefits, carries a significant risk of acute brain injury (ABI). Hypoxic-ischemic brain injury (HIBI) is one of the most common types of ABI in ECMO patients. Various risk factors such as history of hypertension, high day 1 lactate level, low pH, cannulation technique, large peri-cannulation PaCO2 drop (∆PaCO2), and early low pulse pressure, have been associated with the development of HIBI in ECMO patients. The pathogenic mechanisms of HIBI in ECMO are complex and multifactorial, attributing to the underlying pathology requiring initiation of ECMO and the risk of HIBI associated with ECMO itself. HIBI is likely to occur in the peri-cannulation or peri-decannulation time secondary to underlying refractory cardiopulmonary failure before or after ECMO. Current therapeutics target pathological mechanisms, cerebral hypoxia and is-chemia, by employing targeted temperature management in the case of extracorporeal cardiopulmonary resuscitation (eCPR), and optimizing cerebral O2 saturations and cerebral perfusion. This review describes the pathophysiology, neuromonitoring, and therapeutic techniques to improve neurological outcomes in ECMO patients so as to prevent and minimize the morbidity of HIBI. Further studies aimed at stand-ardizing the most relevant neuromonitoring techniques, optimizing cerebral perfusion, and minimizing the severity of HIBI once it occurs will improve long-term neurological outcomes in ECMO patients.

Published
2023

30. Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

Author

Kartsonaki, Christiana, Baillie, J Kenneth, Barrio, Noelia García, Baruch, Joaquín, Beane, Abigail, Blumberg, Lucille, Bozza, Fernando, Broadley, Tessa, Burrell, Aidan, Carson, Gail, Citarella, Barbara Wanjiru, Dagens, Andrew, Dankwa, Emmanuelle A, Donnelly, Christl A, Dunning, Jake, Elotmani, Loubna, Escher, Martina, Farshait, Nataly, Goffard, Jean-Christophe, Gonçalves, Bronner P, Hall, Matthew, Hashmi, Madiha, Sim Lim Heng, Benedict, Ho, Antonia, Jassat, Waasila, Pedrera Jiménez, Miguel, Laouenan, Cedric, Lissauer, Samantha, Martin-Loeches, Ignacio, Mentré, France, Merson, Laura, Morton, Ben, Munblit, Daniel, Nekliudov, Nikita A, Nichol, Alistair D, Singh Oinam, Budha Charan, Ong, David, Panda, Prasan Kumar, Petrovic, Michele, Pritchard, Mark G, Ramakrishnan, Nagarajan, Ramos, Grazielle Viana, Roger, Claire, Sandulescu, Oana, Semple, Malcolm G, Sharma, Pratima, Sigfrid, Louise, Somers, Emily C, Streinu-Cercel, Anca, Taccone, Fabio, Vecham, Pavan Kumar, Kumar Tirupakuzhi Vijayaraghavan, Bharath, Wei, Jia, Wils, Evert-Jan, Ci Wong, Xin, Horby, Peter, Rojek, Amanda, Olliaro, Piero L, ISARIC Clinical Characterisation Group: Ali Abbas, Sheryl Ann Abdukahil, Nurul Najmee Abdulkadir, Ryuzo Abe, Laurent Abel, Lara Absil, Subhash Acharya, Andrew Acker, Elisabeth Adam, Diana Adrião, Saleh Al Ageel, Shakeel Ahmed, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Eman Al Qasim, Razi Alalqam, Angela Alberti, Tala Al-Dabbous, Senthilkumar Alegesan, Cynthia Alegre, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Huda Alfoudri, Imran Ali, Adam Ali, Naseem Ali Shah, Kazali Enagnon Alidjnou, Jeffrey Aliudin, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Aneela Altaf, João Alves, Rita Alves, João Melo Alves, Maria Amaral, Nur Amira, Phoebe Ampaw, Roberto Andini, Claire Andréjak, Andrea Angheben, François Angoulvant, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Muhammad Ashraf, Namra Asif, Mohammad Asim, Jean Baptiste Assie, Amirul Asyraf, Anika Atique, A M Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Laurène Azemar, Cecile Azoulay, Benjamin Bach, Delphine Bachelet, Claudine Badr, Nadia Baig, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Andriy Bal, Mohanaprasanth Balakrishnan, Valeria Balan, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Audrey Barrelet, Cleide Barrigoto, Marie Bartoli, Mustehan Bashir, Romain Basmaci, Muhammad Fadhli Hassin Basri, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Dehbia Benkerrou, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Delphine Bergeaud, Hazel Bergin, José Luis Bernal Sobrino, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Claudia Bianco, Farah Nadiah Bidin, Moirangthem Bikram Singh, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, François Bissuel, Patrick Biston, Laurent Bitker, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Alice Bogaarts, Debby Bogaert, Anne-Hélène Boivin, Pierre-Adrien Bolze, François Bompart, Aurelius Bonfasius, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Dounia Bouhmani, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Jason Bouziotis, Bianca Boxma, Marielle Boyer-Besseyre, Maria Boylan, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Patrick Breen, Dorothy Breen, Kathy Brickell, Shaunagh Browne, Alex Browne, Nicolas Brozzi, Marjolein Brusse-Keizer, Nina Buchtele, Christian Buesaquillo, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Ingrid G Bustos, Denis Butnaru, André Cabie, Susana Cabral, Eder Caceres, Cyril Cadoz, Mia Callahan, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Pauline Caraux-Paz, Sheila Cárcel, Chiara Simona Cardellino, Sofia Cardoso, Filipe Cardoso, Filipa Cardoso, Nelson Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Henry Castrillón, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Christelle Chantalat Auger, Jean-Marc Chapplain, Julie Chas, Allegra Chatterjee, Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Marie-Charlotte Chopin, Ting Soo Chow, Yock Ping Chow, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Emma Clarke, Rolando Claure-Del Granado, Sara Clohisey, Perren J Cobb, Cassidy Codan, Caitriona Cody, Alexandra Coelho, Megan Coles, Gwenhaël Colin, Michael Collins, Sebastiano Maria Colombo, Pamela Combs, Marie Connor, Anne Conrad, Sofía Contreras, Elaine Conway, Graham S Cooke, Mary Copland, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Emma Costigan, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Rachel Cregan, Charles Crepy D'Orleans, Cosimo Cristella, Sabine Croonen, Gloria Crowl, Jonathan Crump, Claudina Cruz, Juan Luis Cruz Berm, Jaime Cruz Rojo, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, Darren Dahly, Heidi Dalton, Jo Dalton, Seamus Daly, Nick Daneman, Corinne Daniel, Jorge Dantas, Frédérick D'Aragon, Menno de Jong, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Lauren Deconninck, Romain Decours, Eve Defous, Isabelle Delacroix, Eric Delaveuve, Karen Delavigne, Nathalie M Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Mehul Desai, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhanger, Alpha Diallo, Sylvain Diamantis, André Dias, Juan Jose Diaz, Priscila Diaz, Rodrigo Diaz, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Félix Djossou, Annemarie B Docherty, Helen Doherty, Arjen M Dondorp, Andy Dong, Maria Donnelly, Sean Donohue, Yoann Donohue, Chloe Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, James Joshua Douglas, Renee Douma, Nathalie Dournon, Triona Downer, Joanne Downey, Mark Downing, Tom Drake, Aoife Driscoll, Murray Dryden, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Marco Echeverria-Villalobos, Siobhan Egan, Carla Eira, Mohammed El Sanharawi, Subbarao Elapavaluru, Brigitte Elharrar, Jacobien Ellerbroek, Philippine Eloy, Tarek Elshazly, Iqbal Elyazar, Isabelle Enderle, Tomoyuki Endo, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Mariano Esperatti, Hélène Esperou, Marina Esposito-Farese, João Estevão, Manuel Etienne, Nadia Ettalhaoui, Anna Greti Everding, Mirjam Evers, Marc Fabre, Isabelle Fabre, Amna Faheem, Arabella Fahy, Cameron J Fairfield, Zul Fakar, Komal Fareed, Pedro Faria, Ahmed Farooq, Hanan Fateena, Arie Zainul Fatoni, Karine Faure, Raphaël Favory, Mohamed Fayed, Niamh Feely, Laura Feeney, Jorge Fernandes, Marília Andreia Fernandes, Susana Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Sílvia Ferreira, Isabel Ferreira, Benigno Ferreira, Ricard Ferrer-Roca, Nicolas Ferriere, Céline Ficko, Claudia Figueiredo-Mello, William Finlayson, Juan Fiorda, Thomas Flament, Clara Flateau, Tom Fletcher, Letizia Lucia Florio, Deirdre Flynn, Claire Foley, Jean Foley, Victor Fomin, Tatiana Fonseca, Patricia Fontela, Simon Forsyth, Denise Foster, Giuseppe Foti, Erwan Fourn, Robert A Fowler, Marianne Fraher, Diego Franch-Llasat, John F Fraser, Christophe Fraser, Marcela Vieira Freire, Ana Freitas Ribeiro, Caren Friedrich, Ricardo Fritz, Stéphanie Fry, Nora Fuentes, Masahiro Fukuda, G Argin, Valérie Gaborieau, Rostane Gaci, Massimo Gagliardi, Jean-Charles Gagnard, Amandine Gagneux-Brunon, Sérgio Gaião, Linda Gail Skeie, Phil Gallagher, Carrol Gamble, Yasmin Gani, Arthur Garan, Rebekha Garcia, Julia Garcia-Diaz, Esteban Garcia-Gallo, Navya Garimella, Denis Garot, Valérie Garrait, Basanta Gauli, Nathalie Gault, Aisling Gavin, Anatoliy Gavrylov, Alexandre Gaymard, Johannes Gebauer, Eva Geraud, Louis Gerbaud Morlaes, Nuno Germano, Praveen Kumar Ghisulal, Jade Ghosn, Marco Giani, Jess Gibson, Tristan Gigante, Morgane Gilg, Elaine Gilroy, Guillermo Giordano, Michelle Girvan, Valérie Gissot, Daniel Glikman, Petr Glybochko, Eric Gnall, Geraldine Goco, François Goehringer, Siri Goepel, Jin Yi Goh, Jonathan Golob, Rui Gomes, Kyle Gomez, Joan Gómez-Junyent, Marie Gominet, Alicia Gonzalez, Patricia Gordon, Isabelle Gorenne, Laure Goubert, Cécile Goujard, Tiphaine Goulenok, Margarite Grable, Jeronimo Graf, Edward Wilson Grandin, Pascal Granier, Giacomo Grasselli, Christopher A Green, Courtney Greene, William Greenhalf, Segolène Greffe, Domenico Luca Grieco, Matthew Griffee, Fiona Griffiths, Ioana Grigoras, Albert Groenendijk, Anja Grosse Lordemann, Heidi Gruner, Yusing Gu, Jérémie Guedj, Martin Guego, Dewi Guellec, Anne-Marie Guerguerian, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Maisa Guimarães de Castro, Thomas Guimard, Marieke Haalboom, Daniel Haber, Hannah Habraken, Ali Hachemi, Amy Hackmann, Nadir Hadri, Fakhir Haidri, Sheeba Hakak, Adam Hall, Sophie Halpin, Jawad Hameed, Ansley Hamer, Raph L Hamers, Rebecca Hamidfar, Terese Hammond, Lim Yuen Han, Rashan Haniffa, Kok Wei Hao, Hayley Hardwick, Ewen M Harrison, Janet Harrison, Samuel Bernard Ekow Harrison, Alan Hartman, Mohd Shahnaz Hasan, Junaid Hashmi, Muhammad Hayat, Ailbhe Hayes, Leanne Hays, Jan Heerman, Lars Heggelund, Ross Hendry, Martina Hennessy, Aquiles Henriquez-Trujillo, Maxime Hentzien, Jaime Hernandez-Montfort, Andrew Hershey, Liv Hesstvedt, Astarini Hidayah, Eibhilin Higgins, Dawn Higgins, Rupert Higgins, Rita Hinchion, Samuel Hinton, Hiroaki Hiraiwa, Haider Hirkani, Hikombo Hitoto, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Oscar Hoiting, Rebecca Holt, Jan Cato Holter, Juan Pablo Horcajada, Koji Hoshino, Ikram Houas, Catherine L Hough, Stuart Houltham, Jimmy Ming-Yang Hsu, Jean-Sébastien Hulot, Stella Huo, Abby Hurd, Iqbal Hussain, Samreen Ijaz, Hajnal-Gabriela Illes, Patrick Imbert, Mohammad Imran, Rana Imran Sikander, Aftab Imtiaz, Hugo Inácio, Carmen Infante Dominguez, Yun Sii Ing, Elias Iosifidis, Mariachiara Ippolito, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Junji Itai, Daniel Ivulich, Danielle Jaafar, Salma Jaafoura, Julien Jabot, Clare Jackson, Nina Jamieson, Victoria Janes, Pierre Jaquet, Coline Jaud-Fischer, Stéphane Jaureguiberry, Jeffrey Javidfar, Denise Jaworsky, Florence Jego, Anilawati Mat Jelani, Synne Jenum, Ruth Jimbo-Sotomayor, Ong Yiaw Joe, Ruth N Jorge García, Cédric Joseph, Mark Joseph, Swosti Joshi, Mercé Jourdain, Philippe Jouvet, Hanna Jung, Anna Jung, Dafsah Juzar, Ouifiya Kafif, Florentia Kaguelidou, Neerusha Kaisbain, Thavamany Kaleesvran, Sabina Kali, Alina Kalicinska, Smaragdi Kalomoiri, Muhammad Aisar Ayadi Kamaluddin, Zul Amali Che Kamaruddin, Nadiah Kamarudin, Paul Kambiya, Kavita Kamineni, Darshana Hewa Kandamby, Chris Kandel, Kong Yeow Kang, Darakhshan Kanwal, Pratap Karpayah, Todd Karsies, Daisuke Kasugai, Anant Kataria, Kevin Katz, Aasmine Kaur, Christy Kay, Hannah Keane, Seán Keating, Pulak Kedia, Claire Kelly, Yvelynne Kelly, Andrea Kelly, Niamh Kelly, Aoife Kelly, Sadie Kelly, Maeve Kelsey, Ryan Kennedy, Kalynn Kennon, Maeve Kernan, Younes Kerroumi, Sharma Keshav, Imrana Khalid, Osama Khalid, Antoine Khalil, Coralie Khan, Irfan Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Amin Khawaja, Krish Kherajani, Michelle E Kho, Saye Khoo, Ryan Khoo, Denisa Khoo, Nasir Khoso, Khor How Kiat, Yuri Kida, Peter Kiiza, Beathe Kiland Granerud, Anders Benjamin Kildal, Jae Burm Kim, Antoine Kimmoun, Detlef Kindgen-Milles, Alexander King, Nobuya Kitamura, Paul Klenerman, Rob Klont, Gry Kloumann Bekken, Stephen R Knight, Robin Kobbe, Chamira Kodippily, Malte Kohns Vasconcelos, Sabin Koirala, Mamoru Komatsu, Caroline Kosgei, Arsène Kpangon, Karolina Krawczyk, Vinothini Krishnan, Sudhir Krishnan, Oksana Kruglova, Deepali Kumar, Ganesh Kumar, Mukesh Kumar, Dinesh Kuriakose, Ethan Kurtzman, Demetrios Kutsogiannis, Galyna Kutsyna, Konstantinos Kyriakoulis, Marie Lachatre, Marie Lacoste, John G Laffey, Marie Lagrange, Fabrice Laine, Olivier Lairez, Sanjay Lakhey, Antonio Lalueza, Marc Lambert, François Lamontagne, Marie Langelot-Richard, Vincent Langlois, Eka Yudha Lantang, Marina Lanza, Cédric Laouénan, Samira Laribi, Delphine Lariviere, Stéphane Lasry, Sakshi Lath, Naveed Latif, Odile Launay, Didier Laureillard, Yoan Lavie-Badie, Andy Law, Teresa Lawrence, Cassie Lawrence, Minh Le, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Paul Le Turnier, Ema Leal, Marta Leal Santos, Todd C Lee, James Lee, Jennifer Lee, Heng Gee Lee, Biing Horng Lee, Yi Lin Lee, Su Hwan Lee, Gary Leeming, Laurent Lefebvre, Bénédicte Lefebvre, Benjamin Lefevre, Sylvie LeGac, Jean-Daniel Lelievre, François Lellouche, Adrien Lemaignen, Véronique Lemee, Anthony Lemeur, Gretchen Lemmink, Ha Sha Lene, Jenny Lennon, Rafael León, Marc Leone, Michela Leone, Quentin Lepiller, François-Xavier Lescure, Olivier Lesens, Mathieu Lesouhaitier, Amy Lester-Grant, Bruno Levy, Yves Levy, Claire Levy-Marchal, Katarzyna Lewandowska, Erwan L'Her, Gianluigi Li Bassi, Janet Liang, Ali Liaquat, Geoffrey Liegeon, Wei Shen Lim, Kah Chuan Lim, Chantre Lima, Lim Lina, Bruno Lina, Andreas Lind, Maja Katherine Lingad, Guillaume Lingas, Sylvie Lion-Daolio, Keibun Liu, Marine Livrozet, Patricia Lizotte, Antonio Loforte, Navy Lolong, Leong Chee Loon, Diogo Lopes, Dalia Lopez-Colon, Jose W Lopez-Revilla, Anthony L Loschner, Paul Loubet, Bouchra Loufti, Guillame Louis, Silvia Lourenco, Lara Lovelace-Macon, Lee Lee Low, Marije Lowik, Jia Shyi Loy, Jean Christophe Lucet, Carlos Lumbreras Bermejo, Carlos M Luna, Olguta Lungu, Liem Luong, Nestor Luque, Dominique Luton, Nilar Lwin, Ruth Lyons, Olavi Maasikas, Oryane Mabiala, Moïse Machado, Gabriel Macheda, Hashmi Madiha, Guillermo Maestro de la Calle, Rafael Mahieu, Sophie Mahy, Ana Raquel Maia, Lars S Maier, Mylène Maillet, Thomas Maitre, Maximilian Malfertheiner, Nadia Malik, Paddy Mallon, Fernando Maltez, Denis Malvy, Victoria Manda, Laurent Mandelbrot, Frank Manetta, Julie Mankikian, Edmund Manning, Aldric Manuel, Ceila Maria Sant Ana Malaque, Flávio Marino, Daniel Marino, Samuel Markowicz, Charbel Maroun Eid, Ana Marques, Catherine Marquis, Brian Marsh, Laura Marsh, Megan Marshal, John Marshall, Celina Turchi Martelli, Dori-Ann Martin, Emily Martin, Guillaume Martin-Blondel, Martin Martinot, Alejandro Martin-Quiros, João Martins, Ana Martins, Nuno Martins, Caroline Martins Rego, Gennaro Martucci, Olga Martynenko, Eva Miranda Marwali, Marsilla Marzukie, David Maslove, Sabina Mason, Sobia Masood, Basri Mat Nor, Moshe Matan, Meghena Mathew, Daniel Mathieu, Mathieu Mattei, Romans Matulevics, Laurence Maulin, Michael Maxwell, Javier Maynar, Thierry Mazzoni, Natalie Mc Evoy, Lisa Mc Sweeney, Colin McArthur, Anne McCarthy, Aine McCarthy, Colin McCloskey, Rachael McConnochie, Sherry McDermott, Sarah E McDonald, Aine McElroy, Samuel McElwee, Victoria McEneany, Allison McGeer, Chris McKay, Johnny McKeown, Kenneth A McLean, Paul McNally, Bairbre McNicholas, Elaine McPartlan, Edel Meaney, Cécile Mear-Passard, Maggie Mechlin, Maqsood Meher, Omar Mehkri, Ferruccio Mele, Luis Melo, Kashif Memon, Joao Joao Mendes, Ogechukwu Menkiti, Kusum Menon, Alexander J Mentzer, Emmanuelle Mercier, Noémie Mercier, Antoine Merckx, Mayka Mergeay-Fabre, Blake Mergler, António Mesquita, Roberta Meta, Osama Metwally, Agnès Meybeck, Dan Meyer, Alison M Meynert, Vanina Meysonnier, Amina Meziane, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Efstathia Mihelis, Vladislav Mihnovit, Hugo Miranda-Maldonado, Nor Arisah Misnan, Tahira Jamal Mohamed, Nik Nur Eliza Mohamed, Asma Moin, David Molina, Elena Molinos, Brenda Molloy, Mary Mone, Agostinho Monteiro, Claudia Montes, Giorgia Montrucchio, Shona C Moore, Sarah Moore, Lina Morales Cely, Lucia Moro, Catherine Motherway, Ana Motos, Hugo Mouquet, Clara Mouton Perrot, Julien Moyet, Caroline Mudara, Aisha Kalsoom Mufti, Ng Yong Muh, Dzawani Muhamad, Jimmy Mullaert, Fredrik Müller, Karl Erik Müller, Syed Muneeb, Nadeem Munir, Laveena Munshi, Aisling Murphy, Lorna Murphy, Marlène Murris, Srinivas Murthy, Himed Musaab, Himasha Muvindi, Gugapriyaa Muyandy, Dimitra Melia Myrodia, Farah Nadia Mohd-Hanafiah, Dave Nagpal, Alex Nagrebetsky, Mangala Narasimhan, Nageswaran Narayanan, Rashid Nasim Khan, Alasdair Nazerali-Maitland, Nadège Neant, Holger Neb, Erni Nelwan, Raul Neto, Emily Neumann, Pauline Yeung Ng, Wing Yiu Ng, Anthony Nghi, Duc Nguyen, Orna Ni Choileain, Niamh Ni Leathlobhair, Prompak Nitayavardhana, Stephanie Nonas, Nurul Amani Mohd Noordin, Marion Noret, Nurul Faten Izzati Norharizam, Lisa Norman, Alessandra Notari, Mahdad Noursadeghi, Karolina Nowicka, Adam Nowinski, Saad Nseir, Jose I Nunez, Nurnaningsih Nurnaningsih, Dwi Utomo Nusantara, Elsa Nyamankolly, Fionnuala O Brien, Annmarie O Callaghan, Annmarie O'Callaghan, Giovanna Occhipinti, Derbrenn OConnor, Max O'Donnell, Tawnya Ogston, Takayuki Ogura, Tak-Hyuk Oh, Sophie O'Halloran, Katie O'Hearn, Shinichiro Ohshimo, Agnieszka Oldakowska, João Oliveira, Larissa Oliveira, Jee Yan Ong, Wilna Oosthuyzen, Anne Opavsky, Peter Openshaw, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Jamel Ortoleva, Javier Osatnik, Linda O'Shea, Miriam O'Sullivan, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Eric Oziol, Maïder Pagadoy, Justine Pages, Mario Palacios, Amanda Palacios, Massimo Palmarini, Giovanna Panarello, Hem Paneru, Lai Hui Pang, Mauro Panigada, Nathalie Pansu, Aurélie Papadopoulos, Rachael Parke, Melissa Parker, Briseida Parra, Taha Pasha, Jérémie Pasquier, Bruno Pastene, Fabian Patauner, Drashti Patel, Mohan Dass Pathmanathan, Luís Patrão, Patricia Patricio, Juliette Patrier, Lisa Patterson, Rajyabardhan Pattnaik, Mical Paul, Christelle Paul, Jorge Paulos, William A Paxton, Jean-François Payen, Kalaiarasu Peariasamy, Giles J Peek, Florent Peelman, Nathan Peiffer-Smadja, Vincent Peigne, Mare Pejkovska, Paolo Pelosi, Ithan D Peltan, Rui Pereira, Daniel Perez, Luis Periel, Thomas Perpoint, Antonio Pesenti, Vincent Pestre, Lenka Petrou, Ventzislava Petrov-Sanchez, Frank Olav Pettersen, Gilles Peytavin, Scott Pharand, Michael Piagnerelli, Walter Picard, Olivier Picone, Maria de Piero, Carola Pierobon, Djura Piersma, Carlos Pimentel, Raquel Pinto, Catarina Pires, Isabelle Pironneau, Lionel Piroth, Ayodhia Pitaloka, Riinu Pius, Laurent Plantier, Hon Shen Png, Julien Poissy, Ryadh Pokeerbux, Maria Pokorska-Spiewak, Sergio Poli, Georgios Pollakis, Diane Ponscarme, Jolanta Popielska, Diego Bastos Porto, Andra-Maris Post, Douwe F Postma, Pedro Povoa, Diana Póvoas, Jeff Powis, Sofia Prapa, Sébastien Preau, Christian Prebensen, Jean-Charles Preiser, Anton Prinssen, Gamage Dona Dilanthi Priyadarshani, Lucia Proença, Sravya Pudota, Oriane Puéchal, Bambang Pujo Semedi, Mathew Pulicken, Gregory Purcell, Luisa Quesada, Vilmaris Quinones-Cardona, Víctor Quirós González, Else Quist-Paulsen, Mohammed Quraishi, Maia Rabaa, Christian Rabaud, Ebenezer Rabindrarajan, Aldo Rafael, Marie Rafiq, Gabrielle Ragazzo, Mutia Rahardjani, Rozanah Abd Rahman, Ahmad Kashfi Haji Ab Rahman, Arsalan Rahutullah, Fernando Rainieri, Giri Shan Rajahram, Pratheema Ramachandran, Ahmad Afiq Ramli, Blandine Rammaert, Asim Rana, Rajavardhan Rangappa, Ritika Ranjan, Christophe Rapp, Aasiyah Rashan, Thalha Rashan, Ghulam Rasheed, Menaldi Rasmin, Indrek Rätsep, Cornelius Rau, Tharmini Ravi, Ali Raza, Andre Real, Stanislas Rebaudet, Sarah Redl, Brenda Reeve, Attaur Rehman, Liadain Reid, Dag Henrik Reikvam, Renato Reis, Jordi Rello, Jonathan Remppis, Martine Remy, Hongru Ren, Hanna Renk, Anne-Sophie Resseguier, Matthieu Revest, Oleksa Rewa, Luis Felipe Reyes, Tiago Reyes, Maria Ines Ribeiro, Antonia Ricchiuto, David Richardson, Denise Richardson, Laurent Richier, Siti Nurul Atikah Ahmad Ridzuan, Jordi Riera, Ana L Rios, Asgar Rishu, Patrick Rispal, Karine Risso, Maria Angelica Rivera Nuñez, Nicholas Rizer, Chiara Robba, André Roberto, Stephanie Roberts, David L Robertson, Olivier Robineau, Ferran Roche-Campo, Paola Rodari, Simão Rodeia, Bernhard Roessler, Pierre-Marie Roger, Emmanuel Roilides, Juliette Romaru, Roberto Roncon-Albuquerque, Mélanie Roriz, Manuel Rosa-Calatrava, Michael Rose, Dorothea Rosenberger, Nurul Hidayah Mohammad Roslan, Andrea Rossanese, Matteo Rossetti, Bénédicte Rossignol, Patrick Rossignol, Stella Rousset, Carine Roy, Benoît Roze, Desy Rusmawatiningtyas, Clark D Russell, Maria Ryan, Maeve Ryan, Steffi Ryckaert, Aleksander Rygh Holten, Isabela Saba, Sairah Sadaf, Musharaf Sadat, Valla Sahraei, Maximilien Saint-Gilles, Pranya Sakiyalak, Nawal Salahuddin, Leonardo Salazar, Jodat Saleem, Gabriele Sales, Stéphane Sallaberry, Charlotte Salmon Gandonniere, Hélène Salvator, Olivier Sanchez, Angel Sanchez-Miralles, Vanessa Sancho-Shimizu, Gyan Sandhu, Zulfiqar Sandhu, Pierre-François Sandrine, Marlene Santos, Shirley Sarfo-Mensah, Bruno Sarmento Banheiro, Iam Claire E Sarmiento, Benjamine Sarton, Ankana Satya, Sree Satyapriya, Rumaisah Satyawati, Egle Saviciute, Parthena Savvidou, Yen Tsen Saw, Justin Schaffer, Tjard Schermer, Arnaud Scherpereel, Marion Schneider, Stephan Schroll, Michael Schwameis, Gary Schwartz, Brendan Scicluna, Janet T Scott, James Scott-Brown, Nicholas Sedillot, Tamara Seitz, Jaganathan Selvanayagam, Mageswari Selvarajoo, Caroline Semaille, Rasidah Bt Senian, Eric Senneville, Claudia Sepulveda, Filipa Sequeira, Tânia Sequeira, Ary Serpa Neto, Pablo Serrano Balazote, Ellen Shadowitz, Syamin Asyraf Shahidan, Mohammad Shamsah, Anuraj Shankar, Shaikh Sharjeel, Catherine A Shaw, Victoria Shaw, Ashraf Sheharyar, Rohan Shetty, Rajesh Mohan Shetty, Haixia Shi, Nisreen Shiban, Mohiuddin Shiekh, Nobuaki Shime, Hiroaki Shimizu, Keiki Shimizu, Sally Shrapnel, Pramesh Sundar Shrestha, Shubha Kalyan Shrestha, Hoi Ping Shum, Nassima Si Mohammed, Ng Yong Siang, Jeanne Sibiude, Atif Siddiqui, Piret Sillaots, Catarina Silva, Rogério Silva, Maria Joao Silva, Wai Ching Sin, Dario Sinatti, Punam Singh, Budha Charan Singh, Pompini Agustina Sitompul, Karisha Sivam, Vegard Skogen, Sue Smith, Benjamin Smood, Coilin Smyth, Michelle Smyth, Morgane Snacken, Dominic So, Tze Vee Soh, Joshua Solomon, Tom Solomon, Agnès Sommet, Rima Song, Tae Song, Jack Song Chia, Michael Sonntagbauer, Azlan Mat Soom, Alberto Sotto, Edouard Soum, Marta Sousa, Ana Chora Sousa, Maria Sousa Uva, Vicente Souza-Dantas, Alexandra Sperry, Elisabetta Spinuzza, B P Sanka Ruwan Sri Darshana, Shiranee Sriskandan, Sarah Stabler, Thomas Staudinger, Stephanie-Susanne Stecher, Trude Steinsvik, Ymkje Stienstra, Birgitte Stiksrud, Eva Stolz, Amy Stone, Adrian Streinu-Cercel, David Stuart, Ami Stuart, Decy Subekti, Gabriel Suen, Jacky Y Suen, Asfia Sultana, Charlotte Summers, Dubravka Supic, Deepashankari Suppiah, Magdalena Surovcová, Suwarti Suwarti, Andrey Svistunov, Sarah Syahrin, Konstantinos Syrigos, Jaques Sztajnbok, Konstanty Szuldrzynski, Shirin Tabrizi, Lysa Tagherset, Shahdattul Mawarni Taib, Ewa Talarek, Sara Taleb, Jelmer Talsma, Renaud Tamisier, Maria Lawrensia Tampubolon, Kim Keat Tan, Yan Chyi Tan, Taku Tanaka, Hiroyuki Tanaka, Hayato Taniguchi, Huda Taqdees, Arshad Taqi, Coralie Tardivon, Pierre Tattevin, M Azhari Taufik, Hassan Tawfik, Richard S Tedder, Tze Yuan Tee, João Teixeira, Sofia Tejada, Marie-Capucine Tellier, Sze Kye Teoh, Vanessa Teotonio, François Téoulé, Pleun Terpstra, Olivier Terrier, Nicolas Terzi, Hubert Tessier-Grenier, Adrian Tey, Alif Adlan Mohd Thabit, Anand Thakur, Zhang Duan Tham, Suvintheran Thangavelu, Vincent Thibault, Simon-Djamel Thiberville, Benoît Thill, Jananee Thirumanickam, Shaun Thompson, Emma C Thomson, David Thomson, Surain Raaj Thanga Thurai, Ryan S Thwaites, Paul Tierney, Vadim Tieroshyn, Peter S Timashev, Jean-François Timsit, Noémie Tissot, Jordan Zhien Yang Toh, Maria Toki, Kristian Tonby, Sia Loong Tonnii, Margarida Torres, Antoni Torres, Rosario Maria Torres Santos-Olmo, Hernando Torres-Zevallos, Michael Towers, Tony Trapani, Théo Treoux, Cécile Tromeur, Ioannis Trontzas, Tiffany Trouillon, Jeanne Truong, Christelle Tual, Sarah Tubiana, Helen Tuite, Jean-Marie Turmel, Lance C W Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, P G Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Timothy M Uyeki, Cristinava Vajdovics, Piero Valentini, Luís Val-Flores, Amélie Valran, Stijn Van de Velde, Marcel van den Berge, Machteld Van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, 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Munblit, Daniel, Nekliudov, Nikita A, Nichol, Alistair D, Singh Oinam, Budha Charan, Ong, David, Panda, Prasan Kumar, Petrovic, Michele, Pritchard, Mark G, Ramakrishnan, Nagarajan, Ramos, Grazielle Viana, Roger, Claire, Sandulescu, Oana, Semple, Malcolm G, Sharma, Pratima, Sigfrid, Louise, Somers, Emily C, Streinu-Cercel, Anca, Taccone, Fabio, Vecham, Pavan Kumar, Kumar Tirupakuzhi Vijayaraghavan, Bharath, Wei, Jia, Wils, Evert-Jan, Ci Wong, Xin, Horby, Peter, Rojek, Amanda, Olliaro, Piero L, ISARIC Clinical Characterisation Group: Ali Abbas, Sheryl Ann Abdukahil, Nurul Najmee Abdulkadir, Ryuzo Abe, Laurent Abel, Lara Absil, Subhash Acharya, Andrew Acker, Elisabeth Adam, Diana Adrião, Saleh Al Ageel, Shakeel Ahmed, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Eman Al Qasim, Razi Alalqam, Angela Alberti, Tala Al-Dabbous, Senthilkumar Alegesan, Cynthia Alegre, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Huda Alfoudri, Imran Ali, Adam Ali, Naseem Ali Shah, Kazali Enagnon Alidjnou, Jeffrey Aliudin, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Aneela Altaf, João Alves, Rita Alves, João Melo Alves, Maria Amaral, Nur Amira, Phoebe Ampaw, Roberto Andini, Claire Andréjak, Andrea Angheben, François Angoulvant, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Muhammad Ashraf, Namra Asif, Mohammad Asim, Jean Baptiste Assie, Amirul Asyraf, Anika Atique, A M Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Laurène Azemar, Cecile Azoulay, Benjamin Bach, Delphine Bachelet, Claudine Badr, Nadia Baig, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Andriy Bal, Mohanaprasanth Balakrishnan, Valeria Balan, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Audrey Barrelet, Cleide Barrigoto, Marie Bartoli, Mustehan Bashir, Romain Basmaci, Muhammad Fadhli Hassin Basri, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Dehbia Benkerrou, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Delphine Bergeaud, Hazel Bergin, José Luis Bernal Sobrino, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Claudia Bianco, Farah Nadiah Bidin, Moirangthem Bikram Singh, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, François Bissuel, Patrick Biston, Laurent Bitker, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Alice Bogaarts, Debby Bogaert, Anne-Hélène Boivin, Pierre-Adrien Bolze, François Bompart, Aurelius Bonfasius, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Dounia Bouhmani, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Jason Bouziotis, Bianca Boxma, Marielle Boyer-Besseyre, Maria Boylan, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Patrick Breen, Dorothy Breen, Patrick Breen, Kathy Brickell, Shaunagh Browne, Alex Browne, Nicolas Brozzi, Marjolein Brusse-Keizer, Nina Buchtele, Christian Buesaquillo, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Ingrid G Bustos, Denis Butnaru, André Cabie, Susana Cabral, Eder Caceres, Cyril Cadoz, Mia Callahan, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Pauline Caraux-Paz, Sheila Cárcel, Chiara Simona Cardellino, Sofia Cardoso, Filipe Cardoso, Filipa Cardoso, Nelson Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Henry Castrillón, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Christelle Chantalat Auger, Jean-Marc Chapplain, Julie Chas, Allegra Chatterjee, Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Marie-Charlotte Chopin, Ting Soo Chow, Yock Ping Chow, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Emma Clarke, Rolando Claure-Del Granado, Sara Clohisey, Perren J Cobb, Cassidy Codan, Caitriona Cody, Alexandra Coelho, Megan Coles, Gwenhaël Colin, Michael Collins, Sebastiano Maria Colombo, Pamela Combs, Marie Connor, Anne Conrad, Sofía Contreras, Elaine Conway, Graham S Cooke, Mary Copland, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Emma Costigan, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Rachel Cregan, Charles Crepy D'Orleans, Cosimo Cristella, Sabine Croonen, Gloria Crowl, Jonathan Crump, Claudina Cruz, Juan Luis Cruz Berm, Jaime Cruz Rojo, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, Darren Dahly, Heidi Dalton, Jo Dalton, Seamus Daly, Nick Daneman, Corinne Daniel, Jorge Dantas, Frédérick D'Aragon, Menno de Jong, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Lauren Deconninck, Romain Decours, Eve Defous, Isabelle Delacroix, Eric Delaveuve, Karen Delavigne, Nathalie M Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Mehul Desai, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhanger, Alpha Diallo, Sylvain Diamantis, André Dias, Juan Jose Diaz, Priscila Diaz, Rodrigo Diaz, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Félix Djossou, Annemarie B Docherty, Helen Doherty, Arjen M Dondorp, Andy Dong, Maria Donnelly, Sean Donohue, Yoann Donohue, Chloe Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, James Joshua Douglas, Renee Douma, Nathalie Dournon, Triona Downer, Joanne Downey, Mark Downing, Tom Drake, Aoife Driscoll, Murray Dryden, Murray Dryden, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Marco Echeverria-Villalobos, Siobhan Egan, Carla Eira, Mohammed El Sanharawi, Subbarao Elapavaluru, Brigitte Elharrar, Jacobien Ellerbroek, Philippine Eloy, Tarek Elshazly, Iqbal Elyazar, Isabelle 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Srinivas Murthy, Himed Musaab, Himasha Muvindi, Gugapriyaa Muyandy, Dimitra Melia Myrodia, Farah Nadia Mohd-Hanafiah, Dave Nagpal, Alex Nagrebetsky, Mangala Narasimhan, Nageswaran Narayanan, Rashid Nasim Khan, Alasdair Nazerali-Maitland, Nadège Neant, Holger Neb, Erni Nelwan, Raul Neto, Emily Neumann, Pauline Yeung Ng, Wing Yiu Ng, Anthony Nghi, Duc Nguyen, Orna Ni Choileain, Niamh Ni Leathlobhair, Prompak Nitayavardhana, Stephanie Nonas, Nurul Amani Mohd Noordin, Marion Noret, Nurul Faten Izzati Norharizam, Lisa Norman, Alessandra Notari, Mahdad Noursadeghi, Karolina Nowicka, Adam Nowinski, Saad Nseir, Jose I Nunez, Nurnaningsih Nurnaningsih, Dwi Utomo Nusantara, Elsa Nyamankolly, Fionnuala O Brien, Annmarie O Callaghan, Annmarie O'Callaghan, Giovanna Occhipinti, Derbrenn OConnor, Max O'Donnell, Tawnya Ogston, Takayuki Ogura, Tak-Hyuk Oh, Sophie O'Halloran, Katie O'Hearn, Shinichiro Ohshimo, Agnieszka Oldakowska, João Oliveira, Larissa Oliveira, Jee Yan Ong, Wilna Oosthuyzen, Anne 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Helen Tuite, Jean-Marie Turmel, Lance C W Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, P G Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Timothy M Uyeki, Cristinava Vajdovics, Piero Valentini, Luís Val-Flores, Amélie Valran, Stijn Van de Velde, Marcel van den Berge, Machteld Van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, Frank van Someren Greve, Ilonka van Veen, Hugo Van Willigen, Noémie Vanel, Henk Vanoverschelde, Pooja Varghese, Michael Varrone, Shoban Raj Vasudayan, Charline Vauchy, Shaminee Veeran, Aurélie Veislinger, Sebastian Vencken, Sara Ventura, Annelies Verbon, James Vickers, José Ernesto Vidal, César Vieira, Deepak Vijayan, Joy Ann Villanueva, Judit Villar, Pierre-Marc Villeneuve, Andrea Villoldo, Gayatri Vishwanathan, Benoit Visseaux, Hannah Visser, Chiara Vitiello, Harald Vonkeman, Fanny Vuotto, Suhaila Abdul Wahab, Noor Hidayu Wahab, Nadirah Abdul Wahid, Marina Wainstein, Wan Fadzlina Wan Muhd Shukeri, Chih-Hsien Wang, Steve Webb, Katharina Weil, Tan Pei Wen, Sanne Wesselius, T Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Suzette Willems, Virginie Williams, Calvin Wong, Yew Sing Wong, Teck Fung Wong, Natalie Wright, Gan Ee Xian, Lim Saio Xian, Kuan Pei Xuan, Ioannis Xynogalas, Siti Rohani Binti Mohd Yakop, Masaki Yamazaki, Yazdan Yazdanpanah, Nicholas Yee Liang Hing, Cécile Yelnik, Chian Hui Yeoh, Stephanie Yerkovich, Toshiki Yokoyama, Hodane Yonis, Obada Yousif, Saptadi Yuliarto, Akram Zaaqoq, Marion Zabbe, Kai Zacharowski, Masliza Zahid, Maram Zahran, Nor Zaila Binti Zaidan, Maria Zambon, Miguel Zambrano, Alberto Zanella, Konrad Zawadka, Nurul Zaynah, Hiba Zayyad, Alexander Zoufaly, David Zucman, University of Oxford, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), This work was made possible by the UK Foreign, Commonwealth and Development Office, Wellcome (215091/Z/18/Z, 205228/Z/16/Z, 220757/Z/20/Z), Bill & Melinda Gates Foundation (OPP1209135), UK Medical Research Council Clinical Research Training Fellowship (MR/V001671/1), the philanthropic support of the donors to the University of Oxford’s COVID-19 Research Response Fund, CIHR Coronavirus Rapid Research Funding Opportunity (OV2170359) and the co-ordination in Canada by Sunnybrook Research Institute, endorsement of the Irish Critical Care—Clinical Trials Group, co-ordination in Ireland by the Irish Critical Care—Clinical Trials Network at University College Dublin and funding by the Health Research Board of Ireland (CTN-2014–12), the Rapid European COVID-19 Emergency Response research (RECOVER) (H2020 project 101003589) and European Clinical Research Alliance on Infectious Diseases (ECRAID) (965313), the COVID clinical management team, AIIMS, Rishikesh, India, the COVID-19 Clinical Management team, Manipal Hospital Whitefield, Bengaluru, India, Cambridge NIHR Biomedical Research Centre, the dedication and hard work of the Groote Schuur Hospital Covid ICU Team, support by the Groote Schuur nursing and University of Cape Town registrar bodies co-ordinated by the Division of Critical Care at the University of Cape Town, the Liverpool School of Tropical Medicine and the University of Oxford, the dedication and hard work of the Norwegian SARS-CoV-2 study team, the Research Council of Norway (grant no. 312780) and a philanthropic donation from Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner, Imperial NIHR Biomedical Research Centre, the Comprehensive Local Research Networks of which PJMO is an NIHR Senior Investigator (NIHR201385), Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 115523 COMBACTE, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007– 2013) and EFPIA companies, in-kind contribution, the French COVID cohort (NCT04262921) is sponsored by INSERM and is funded by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n 20–0424), Stiftungsfonds zur Förderung der Bekämpfung der Tuberkulose und anderer Lungenkrankheiten of the City of Vienna (project no. APCOV22BGM), Italian Ministry of Health ‘Fondi Ricerca corrente–L1P6’ to IRCCS Ospedale Sacro Cuore–Don Calabria, Australian Department of Health grant (3273191), Gender Equity Strategic Fund at University of Queensland, Artificial Intelligence for Pandemics (A14PAN) at University of Queensland, the Australian Research Council Centre of Excellence for Engineered Quantum Systems (EQUS, CE170100009), the Prince Charles Hospital Foundation, Australia, grants from Instituto de Salud Carlos III, Ministerio de Ciencia, Spain, Brazil, National Council for Scientific and Technological Development (scholarship no. 303953/2018–7), the Firland Foundation, Shoreline, Washington, USA, a grant from foundation Bevordering Onderzoek Franciscus, the South Eastern Norway Health Authority and the Research Council of Norway, and preparedness work conducted by the Short PeRiod IncideNce sTudy of Severe Acute Respiratory Infection. Data and Material provision was supported by grants from the National Institute for Health Research (NIHR, award CO-CIN-01), the Medical Research Council (MRC, and grant MC_PC_19059) and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with PHE (award no. 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award no. 200927), Liverpool Experimental Cancer Medicine Centre (grant no. C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award no. IS-BRC-1215–20013) and NIHR Clinical Research Network providing infrastructure support.

Subjects
Male, Epidemiology, MESH: Hospitalization, MESH: Proportional Hazards Models, MESH: Risk Factors, Risk Factors, MESH: Child, cohort study, MESH: COVID-19, Humans, MESH: SARS-CoV-2, Child, Proportional Hazards Models, MESH: Humans, MESH: Middle Aged, SARS-CoV-2, COVID-19, risk of death, General Medicine, Middle Aged, co-morbidities, symptoms, treatments, MESH: Male, Hospitalization, Intensive Care Units, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19/therapy
Abstract

Background We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Conclusions Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.

Published
2023

31. Prevalence and outcomes of acute respiratory distress syndrome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

Author

Tracey H. Fan, Merry Huang, Carrie Price, Lavienraj Premraj, Nivedha V. Kannapadi, Jose I. Suarez, and Sung-Min Cho

Subjects
Advanced and Specialized Nursing, Psychiatry and Mental health, Neurology (clinical)
Abstract

Background: In this study, we aimed to investigate the prevalence, timing, risk factors, and outcomes of acute respiratory distress syndrome (ARDS) in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods: PubMed and four other databases were searched for randomized controlled trials (RCTs) and observational studies of patients 18 years or older through October 20, 2021. Study quality was assessed, using the Cochrane Risk of Bias tool for RCTs and the Newcastle-Ottawa Scale for cohort and case-control studies. High-grade aSAH was defined as a Hunt-Hess grade≥3 and/or a modified Fisher score≥3. A good neurological outcome was defined as a Glasgow Outcome Scale score ≥4. Random-effects meta-analyses were conducted to estimate the pooled outcome prevalence and 95% confidence interval (CI). Results: Eleven observational studies (n=6,107) met the inclusion criteria. Overall, 15% of the patients (95% CI=10.5–20.0; I2=97.8%) developed ARDS after aSAH, with a mean time of 3 days (95% CI=1.9–3.7; I2=54%). Overall survival at discharge was 80% (95% CI=75–86; I2=96%), and 67% of aSAH patients (95% CI=54.9–78.9; I2=94%) had a good neurological outcome at any time. The aSAH cohort without ARDS had a higher rate of survival than those with ARDS (79% vs. 49%, P=0.028). Male sex, patients with a high-grade aSAH, patients who developed pneumonia, and systemic inflammatory response syndrome during hospital admission were at a higher risk of developing ARDS.Conclusion: In this meta-analysis, approximately one in six patients developed ARDS after aSAH, with a mean time of 3 days from the initial presentation, and ARDS was associated with increased mortality.

Published
2022

32. The association of modifiable mechanical ventilation settings, blood gas changes and survival on extracorporeal membrane oxygenation for cardiac arrest

Author

Joseph E, Tonna, Craig H, Selzman, Jason A, Bartos, Angela P, Presson, Zhining, Ou, Yeonjung, Jo, Lance B, Becker, Scott T, Youngquist, Ravi R, Thiagarajan, M, Austin Johnson, Sung-Min, Cho, Peter, Rycus, and Heather T, Keenan

Subjects
Adult, Extracorporeal Membrane Oxygenation, Emergency Medicine, Humans, Prospective Studies, Emergency Nursing, Cardiology and Cardiovascular Medicine, Respiration, Artificial, Cardiopulmonary Resuscitation, Article, Heart Arrest, Retrospective Studies
Abstract

RESEARCH QUESTION: Given the relative independence of ventilator settings from gas exchange and plasticity of blood gas values during extracorporeal cardiopulmonary resuscitation (ECPR), do mechanical ventilation parameters and blood gas values influence survival? METHODS: Observational cohort study of 7,488 adult patients with ECPR from the Extracorporeal Life Support Organization (ELSO) Registry. We performed case-mix adjustment for severity of illness and patient type using generalized estimating equation logistic regression to determine factors associated with hospital survival accounting for clustering by center, standardizing variables by 1 standard deviation (SD) of their values. We examined non-linear relationships between ventilatory and blood gas values with hospital survival. RESULTS: Hospital survival was decreased with higher PaO(2) on ECMO (OR 0.69, per 1SD increase [95% CI 0.64, 0.74]; p 20cmH(2)0 (OR 0.69, per 1SD [0.64, 0.75]; p

Published
2022

33. Myasthenic crisis

Author

Benjamin Claytor, Sung‐Min Cho, and Yuebing Li

Subjects
Cellular and Molecular Neuroscience, Physiology, Physiology (medical), Neurology (clinical)
Published
2023

34. Tracheostomy timing and outcome in critically ill patients with stroke: a meta-analysis and meta-regression

Author

Lavienraj Premraj, Christopher Camarda, Nicole White, Daniel Agustin Godoy, Brian H. Cuthbertson, Patricia R. M. Rocco, Paolo Pelosi, Chiara Robba, Jose I. Suarez, Sung-Min Cho, and Denise Battaglini

Subjects
Critical Care and Intensive Care Medicine
Abstract

Background Stroke patients requiring mechanical ventilation often have a poor prognosis. The optimal timing of tracheostomy and its impact on mortality in stroke patients remains uncertain. We performed a systematic review and meta-analysis of tracheostomy timing and its association with reported all-cause overall mortality. Secondary outcomes were the effect of tracheostomy timing on neurological outcome (modified Rankin Scale, mRS), hospital length of stay (LOS), and intensive care unit (ICU) LOS. Methods We searched 5 databases for entries related to acute stroke and tracheostomy from inception to 25 November 2022. We adhered to PRISMA guidance for reporting systematic reviews and meta-analyses. Selected studies included (1) ICU-admitted patients who had stroke (either acute ischaemic stroke, AIS or intracerebral haemorrhage, ICH) and received a tracheostomy (with known timing) during their stay and (2) > 20 tracheotomised. Studies primarily reporting sub-arachnoid haemorrhage (SAH) were excluded. Where this was not possible, adjusted meta-analysis and meta-regression with study-level moderators were performed. Tracheostomy timing was analysed continuously and categorically, where early ( 10 days) timing was defined per the protocol of SETPOINT2, the largest and most recent randomised controlled trial on tracheostomy timing in stroke patients. Results Thirteen studies involving 17,346 patients (mean age = 59.8 years, female 44%) met the inclusion criteria. ICH, AIS, and SAH comprised 83%, 12%, and 5% of known strokes, respectively. The mean time to tracheostomy was 9.7 days. Overall reported all-cause mortality (adjusted for follow-up) was 15.7%. One in five patients had good neurological outcome (mRS 0–3; median follow-up duration was 180 days). Overall, patients were ventilated for approximately 12 days and had an ICU LOS of 16 days and a hospital LOS of 28 days. A meta-regression analysis using tracheostomy time as a continuous variable showed no statistically significant association between tracheostomy timing and mortality (β = − 0.3, 95% CI = − 2.3 to 1.74, p = 0.8). Early tracheostomy conferred no mortality benefit when compared to late tracheostomy (7.8% vs. 16.4%, p = 0.7). Tracheostomy timing was not associated with secondary outcomes (good neurological outcome, ICU LOS and hospital LOS). Conclusions In this meta-analysis of over 17,000 critically ill stroke patients, the timing of tracheostomy was not associated with mortality, neurological outcomes, or ICU/hospital LOS. Trial registration: PROSPERO—CRD42022351732 registered on 17th of August 2022.

Published
2023

35. High Prevalence of Acute Brain Injury on Brain Magnetic Resonance Imaging in Acute Respiratory Distress Syndrome

Author

Merry Huang, Aron Gedansky, Catherine E. Hassett, Aaron Shoskes, Abhijit Duggal, Ken Uchino, Sung-Min Cho, and Andrew Blake Buletko

Abstract

Objective: Acute Respiratory Distress Syndrome(ARDS) is an acute inflammatory respiratory failure condition that may be associated with acute brain injury (ABI). We aimed to describe the prevalence and types of ABI detected by brain MRI among ARDS patients. Methods: We retrospectively reviewed and collected data on ABI as detected by brain MRI during index hospitalization of all ARDS patients at a single tertiary center in the United States from January 2010 to October 2018. ABIs were classified as cerebral ischemia (ischemic infarct and hypoxic ischemic brain injury) or cerebral hemorrhage (intraparenchymal hemorrhage, cerebral microbleeds, subarachnoid hemorrhage, and subdural hematoma). Descriptive statistics were conducted. Results: Of the 678 ARDS patients, 66 (9.7%) underwent brain MRI during their ARDS illness. The most common indication for brain MRI was encephalopathy (45.4%) and the median time from hospital admission to MRI was 10 days (interquartile range 4-17). Of 66, 29 (44%) had MRI evidence of ABI including cerebral ischemia in 33% (22/66) and cerebral hemorrhage in 21% (14/66). Among those with cerebral ischemia, common findings were bilateral globus pallidus infarcts (n=7, 32%), multifocal infarcts (n=5, 23%), and diffuse hypoxic ischemic brain injury (n=3, 14%). Of those with cerebral hemorrhage, common findings were cerebral microbleeds (n=12, 86%) and intraparenchymal hemorrhage (n=2, 14%). ARDS patients with cerebral hemorrhage had significantly greater use of rescue therapies including prone positioning (28.6% vs 5.8%, p = 0.03), inhaled vasodilator (35.7% vs 11.5%, p = 0.046), and recruitment maneuver (14.3% vs 0%, p = 0.04). Conclusion: Among selected patients with ARDS who underwent brain MRI, almost a half had ABI most commonly including bilateral globus pallidus infarcts and cerebral microbleeds.

Published
2023

37. Characteristics of Delirium and Its Association with Sedation and In-Hospital Mortality in COVID-19 Patients on Veno-venous Extracorporeal Membrane Oxygenation

Author

Philip Y Sun, Jonathon Fanning, Anna Peeler, Benjamin Shou, John Lindsley, Giorgio Caturegli, Glenn Whitman, Stephanie Cha, Bo Soo Kim, and Sung-Min Cho

Abstract

Background Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used in patients with COVID-19 acute respiratory distress syndrome (ARDS). We aim to assess the characteristics of delirium and describe its association with sedation and in-hospital mortality. Methods We retrospectively reviewed adult patients on VV-ECMO for severe COVID-19 ARDS in the Johns Hopkins Hospital ECMO registry in 2020-2021. Delirium was assessed by the Confusion Assessment Method for the ICU when patients scored -3 or above on Richmond Agitation-Sedation Scale (RASS). Primary outcomes were delirium prevalence while on VV-ECMO and categorization of VV-ECMO days based on delirium status. Results Of 47 patients (median age=51) with 6 in a persistent coma, 40 of the remaining 41 patients (98%) had ICU delirium. Delirium in the survivors (n=21) and non-survivors (n=26) was first detected at a similar time point (day 9.5[5, 14] vs. 8.5[5, 21], p=0.56) with similar total delirium days (9.5[3.3, 16.8] vs. 9.0[4.3, 28.3], p=0.43), but the RASS scores on VV-ECMO were numerically lower in non-survivors (-3.72[-4.42, -2.96] vs. -3.10[-3.91, -2.21], p=0.06). Non-survivors had significantly prolonged median delirium days (27.3[17.4, 46.4] vs. 17.0[9.9, 28], p=0.04), delirium-unassessable days on VV-ECMO with a RASS of -4/-5 (23.0[16.3, 38.3] vs. 17.0[6, 23], p=0.03), and total VV-ECMO days (44.5[20.5, 74.3] vs. 27.0[21, 38], p=0.04). The proportion of delirium-present days correlated with RASS (r=0.64, p

Published
2023

40. Factors associated with rebleeding after coil embolization in patients with aneurysmal subarachnoid hemorrhage

Author

Sung Min Cho, Jinsu Pyen, Yeongyu Jang, Jong Wook Choi, Kum Whang, Jongyeon Kim, Donghee Kim, and Younmoo Koo

Subjects
medicine.medical_specialty, Subarachnoid hemorrhage, business.industry, Mortality rate, medicine.medical_treatment, Odds ratio, Perioperative, medicine.disease, Confidence interval, Surgery, Aneurysm, medicine, In patient, Embolization, business
Abstract

Objective: Aneurysmal subarachnoid hemorrhage (aSAH) has a high mortality rate, and hemorrhage amounts and perioperative rebleeding importantly determines prognosis. However, despite adequate treatment, prognosis is poor in many ruptured aneurysm cases. In this study, we identified and evaluated factors related to perioperative rebleeding in patients with aSAH.Methods: The medical and surgical records of 166 patients that underwent endovascular embolization for a ruptured cerebral aneurysm at a single institution from 2014 to 2016 were retrospectively analyzed to identify risk factors of rebleeding. All patients were examined for risk factors and evaluated for increased hemorrhage by brain computed tomography at 3 days after surgery.Results: This series included 54 men (32.5%) and 112 women (67.5%) of mean age 58.3±14.3 years. After procedures, 26 patients (15.7%) experienced rebleeding, and 1 of these (0.6%) experienced an intraoperative aneurysmal rupture. External ventricular drainage (EVD) (odds ratio [OR] 5.389, [95% confidence interval (CI) 1.171- 24.801]) and modified Fisher grade (OR 2.037, [95% CI 1.077-3.853]) were found to be independent risk factors of rebleeding, and perioperative rebleeding was strongly associated with patient outcomes (p＜0.001).Conclusions: We concluded the rebleeding risk after aSAH is greater in patients with large hemorrhage amounts and a high pre-operative modified Fisher grade, and thus, we caution neurosurgeons should take care in such cases.

Published
2022

41. Arterial Carbon Dioxide and Acute Brain Injury in Venoarterial Extracorporeal Membrane Oxygenation

Author

Benjamin L. Shou, Chin Siang Ong, Alice L. Zhou, Mais N. Al-Kawaz, Eric Etchill, Katherine Giuliano, Jie Dong, Errol Bush, Bo Soo Kim, Chun Woo Choi, Glenn Whitman, and Sung-Min Cho

Subjects
Adult, Male, Biomedical Engineering, Biophysics, Bioengineering, General Medicine, Middle Aged, Carbon Dioxide, Article, Femoral Artery, Biomaterials, Extracorporeal Membrane Oxygenation, Brain Injuries, Humans, Female, Intracranial Hemorrhages, Retrospective Studies
Abstract

Acute brain injury (ABI) occurs frequently in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO). We examined the association between peri-cannulation arterial carbon dioxide tension (PaCO 2 ) and ABI with granular blood gas data. We retrospectively analyzed adult patients who underwent VA-ECMO at a tertiary care center with standardized neuromonitoring. Pre- and post-cannulation PaCO 2 were defined as the mean of all PaCO 2 values in the 12 hours before and after cannulation, respectively. Peri-cannulation PaCO 2 drop (∆PaCO 2 ) equaled pre- minus post-cannulation PaCO 2 . ABI included intracranial hemorrhage (ICH), ischemic stroke, hypoxic-ischemic brain injury, cerebral edema, seizure, and brain death. Univariable logistic regression analysis was performed for the presence of ABI. Out of 129 VA-ECMO patients (median age = 60, 63% male), 43 (33%) patients experienced ABI. Patients had a median of 11 (interquartile range: 8-14) peri-cannulation PaCO 2 values. Comparing patients with and without ABI, pre-cannulation (39 vs. 42 mm Hg; p = 0.38) and post-cannulation (37 vs. 36 mm Hg; p = 0.82) PaCO 2 were not different. However, higher pre-cannulation PaCO 2 (odds ratio [OR] = 2.10; 95% confidence interval [CI] = 1.10-4.00; p = 0.02) and larger ∆PaCO 2 (OR = 2.69; 95% CI = 1.18-6.13; p = 0.02) were associated with ICH. In conclusion, in a cohort with granular arterial blood gas (ABG) data and a standardized neuromonitoring protocol, higher pre-cannulation PaCO 2 and larger ∆PaCO 2 were associated with increased prevalence of ICH.

Published
2022

42. Updated Trans-Ethnic Meta-Analysis of Associations between Inflammation-Related Genes and Intracranial Aneurysm.

Author

Eun Pyo Hong, Sung Min Cho, Jong Kook Rhim, Jeong Jin Park, Jun Hyong Ahn, Dong Hyuk Youn, Jong-Tae Kim, Chan Hum Park, Younghyurk Lee, and Jin Pyeong Jeon

Subjects
*INTRACRANIAL aneurysms, *STATISTICAL power analysis, *GENOME-wide association studies, *SEARCH engines, *GENE mapping
Abstract

Objective: We performed an expanded multi-ethnic meta-analysis to identify associations between inflammation-related loci with intracranial aneurysm (IA) susceptibility. This meta-analysis possesses increased statistical power as it is based on the most data ever evaluated. Methods: We searched and reviewed relevant literature through electronic search engines up to August 2022. Overall estimates were calculated under the fixed- or random-effect models using pooled odds ratio (OR) and 95% confidence intervals (CIs). Subgroup analyses were performed according to ethnicity. Results: Our meta-analysis enrolled 15 studies and involved 3070 patients and 5528 controls including European, Asian, Hispanic, and mixed ethnic populations. Of 17 inflammation-related variants, the rs1800796 locus (interleukin [IL]-6) showed the most significant genome-wide association with IA in East-Asian populations, including 1276 IA patients and 1322 controls (OR, 0.65; 95% CI, 0.56-0.75; p=3.24×10-9) under a fixed-effect model. However, this association was not observed in the European population (OR, 1.09; 95% CI, 0.80-1.47; p=0.5929). Three other variants, rs16944 (IL-1ß), rs2195940 (IL-12B), and rs1800629 (tumor necrosis factor-a) showed a statistically nominal association with IA in both the overall, as well as East-Asian populations (0.01

Published
2023
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44. Prevalence and Outcome of Acute Respiratory Distress Syndrome in Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Author

Sung Min Cho, Merry Huang, Chiara Robba, Carrie Price, Tracey H. Fan, Aron Gedansky, and Adrian V. Hernandez

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, ARDS, medicine.medical_specialty, Adolescent, Traumatic brain injury, Population, Acute brain injury, Cochrane Library, law.invention, Cohort Studies, Randomized controlled trial, Interquartile range, law, Internal medicine, Brain Injuries, Traumatic, Prevalence, medicine, Acute lung injury, Humans, education, Respiratory Distress Syndrome, education.field_of_study, Acute respiratory distress syndrome, business.industry, medicine.disease, Case-Control Studies, Meta-analysis, Cohort, Female, business, Neurogenic pulmonary edema
Abstract

Objectives Acute respiratory distress syndrome (ARDS) in patients with traumatic brain injury (TBI) is associated with increased mortality. Information on the prevalence of ARDS and its neurological outcome after TBI is sparse. We aimed to systematically review the prevalence, risk factors, and outcome of ARDS in TBI population. Data Sources PubMed and four other databases (Embase, Cochrane Library, Web of Science Core Collection, and Scopus) from inception to July 6, 2020. Study Selection Randomized controlled trials (RCTs) and observational studies in patients older than 18 years old. Data Extraction Two independent reviewers extracted the data. Study quality was assessed by the Cochrane Risk of Bias tool for RCTs, the Newcastle–Ottawa Scale for cohort and case–control studies. Good neurological outcome was defined as Glasgow Outcome Scale ≥ 4. Random-effects meta-analyses were conducted to estimate pooled outcome prevalence and their 95% confidence intervals (CI). Data Synthesis We included 20 studies (n = 2830) with median age of 44 years (interquartile range [IQR] = 35–47, 64% male) and 79% (n = 2237) suffered severe TBI. In meta-analysis, 19% patients (95% CI = 0.13–0.27, I2 = 93%) had ARDS after TBI. The median time from TBI to ARDS was 3 days (IQR = 2–5). Overall survival at discharge for the TBI cohort was 70% (95% CI = 0.64–0.75; I2 = 85%) and good neurological outcome at any time was achieved in 31% of TBI patients (95% CI = 0.23–0.40; I2 = 88%). TBI cohort without ARDS had higher survival (67% vs. 57%, p = 0.01) and good neurological outcomes (34% vs. 23%, p = 0.02) compared to those with ARDS. We did not find any specific risk factors for developing ARDS. Conclusion In this meta-analysis, approximately one in five patients had ARDS shortly after TBI with the median time of 3 days. The presence of ARDS was associated with worse neurological outcome and mortality in TBI. Further research on prevention and intervention strategy of TBI-associated ARDS is warranted. Supplementary Information The online version contains supplementary material available at 10.1007/s00408-021-00491-1.

Published
2021

45. Kinematics after cervical laminoplasty: risk factors for cervical kyphotic deformity after laminoplasty

Author

Sung Min Cho, Jaehyung Cha, Junseok W. Hur, Bum-Joon Kim, and Se Hoon Kim

Subjects
Lordosis, medicine.medical_treatment, Kyphosis, Context (language use), Spinal Cord Diseases, Laminoplasty, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Spinal cord compression, medicine, Cervical spondylosis, Humans, Orthopedics and Sports Medicine, Retrospective Studies, Orthodontics, 030222 orthopedics, Neck pain, business.industry, Middle Aged, medicine.disease, Biomechanical Phenomena, Treatment Outcome, Cervical Vertebrae, Surgery, Spondylosis, Neurology (clinical), medicine.symptom, Range of motion, business, 030217 neurology & neurosurgery
Abstract

Laminoplasty of the cervical spine is widely used as an effective surgical method to treat compressive myelopathy of the cervical spine; however, there is an adverse effect of kyphosis after surgery. The risk factors or predictors of kyphosis have not been sufficiently evaluated.To assess the risk factors for kyphosis following laminoplasty.Retrospective study.Patients diagnosed with cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament (OPLL) who underwent laminoplasty between May 2011 and October 2018 were enrolled.Changes in lordosis and range of motion (ROM).Radiological imaging data were collected from simple neutral and flexion-extension radiographs at baseline and at 2-year follow-up. The ROM from the neutral position to complete flexion was defined as the flexion capacity, and the ROM from the neutral position to complete extension was defined as the extension capacity.This study included 53 patients (mean age, 59.3 years). Multivariate linear regression analysis revealed that, the smaller the preoperative extension capacity, the greater was the decrease in lordosis (p=.025), while the larger the T1 slope, the greater was the decrease in lordosis following laminoplasty (p= .008). Correlation analysis revealed that C2-7 lordosis increased with increasing baseline T1 slope before surgery (p.01). In patients with large preoperative C2-7 lordosis, the postoperative decrease in ROM tended to be greater (p= .028). However, the degree of lordosis and ROM reduction did not demonstrate a clear correlation with the clinical outcomes at 2 years after surgery.Kyphotic changes in the cervical spine following laminoplasty were related to preoperative radiological parameters. The greater the preoperative extension capacity, the lower was the decrease in lordosis, and the greater the T1 slope, the greater was the decrease in lordosis.

Published
2021

46. Long-Term Neurocognitive Outcome in Patients With Continuous Flow Left Ventricular Assist Device

Author

Darlene Floden, Randall C. Starling, Nahush A. Mokadam, Sung Min Cho, Nicholas Hiivala, Jeffrey J. Teuteberg, Song Li, Kristie Wallace, Susan M. Joseph, David L. Tirschwell, Ken Uchino, Joseph G. Rogers, Francis D. Pagani, and Claudius Mahr

Subjects
Heart Failure, Male, medicine.medical_specialty, business.industry, Continuous flow, medicine.medical_treatment, Cognition, medicine.disease, Outcome (game theory), Term (time), Stroke, Heart failure, Internal medicine, Ventricular assist device, medicine, Cardiology, Humans, In patient, Heart-Assist Devices, Cardiology and Cardiovascular Medicine, business, Neurocognitive, Retrospective Studies
Abstract

The authors sought to examine the long-term cognitive outcome of patients with continuous flow left ventricular assist device (CF-LVAD).Data on long-term neurocognitive outcome in LVAD are limited. We examined the neurocognitive outcome of patients who received a CF-LVAD as destination therapy.Patients with HeartWare (HVAD) and HeartMate II who were enrolled in the ENDURANCE and ENDURANCE Supplemental trials were eligible. Cognition was evaluated with neuropsychological testing preoperatively and at 6, 12, and 24 months after implantation. General linear models identified demographic, disease, and treatment factors that predicted decline on each neurocognitive measure.Of 668 patients who completed baseline testing and at least 1 follow-up evaluation, 552 were impaired at baseline on at least 1 cognitive measure. At each follow-up, approximately 23% of tested patients declined and 20% improved relative to baseline on at least 1 cognitive measure. Of those who were intact at baseline, only 10%-12% declined in delayed memory and 11%-16% declined in executive function at all 3 follow-ups. For patients impaired at baseline, delayed memory decline was associated with the HVAD device and male sex, whereas executive function decline was associated with the HVAD device and stroke during CF-LVAD support. For patients intact at baseline, male sex and history of hypertension were associated with decline in immediate memory and executive function, respectively.Neurocognitive function remained stable or improved for most patients (∼80%) with CF-LVAD at 6, 12, and 24 months after implantation. Male sex, hypertension, HVAD, and stroke were associated with cognitive decline.

Published
2021

47. Emergent Vertebral Artery Embolization during C12 Screw Fixation for Rheumatoid Arthritis

Author

Sung Min Cho, Kum Whang, Donghee Kim, Younkyu Jang, and Jongyeon Kim

Subjects
medicine.medical_specialty, Nerve root, business.industry, Spondyloarthropathy, Therapeutic Embolization, Vertebral artery, medicine.medical_treatment, Case Report, Rheumatoid Arthritis, medicine.disease, Screw fixation, Surgery, Dissection, medicine.artery, Rheumatoid arthritis, medicine, Embolization, business, Fixation (histology)
Abstract

The subaxial screw fixation technique is commonly used for fixation in a wide range of cervical diseases, including traumatic, degenerative, and neoplastic diseases, rheumatoid arthritis (RA), and spondyloarthropathy. Although it is regarded as a relatively safe procedure, several complications may be encountered during surgery, such as vertebral artery (VA) and nerve root injuries, facet violation, and mass fracture. We report a case of endovascular embolization after VA injury during a high cervical spinal surgery. A 48-year-old woman was scheduled for C-1-2-3 posterior fixation. Plain radiography of the cervical spine revealed a severely unstable state. During dissection around the C1 lateral mass on the right side, sudden brisk arterial bleeding was observed. On vertebral angiography, flow voiding was noted above the right V3 portion. After checking patent collateral flow from the contralateral VA, routine coil embolization was performed to pack the V3 segment. Iatrogenic vascular injuries due to spinal surgery are rare but serious complications. For patients with RA, we recommend careful preoperative evaluation before a high cervical surgical procedure to avoid iatrogenic VA injury and endovascular interventions that are safe and effective in the diagnosis and treatment of such vascular injuries.

Published
2021

48. Brain injury in extracorporeal cardiopulmonary resuscitation: translational to clinical research

Author

Sung Min Cho, Chun Woo Choi, and Christopher Wilcox

Subjects
Clinical research, business.industry, Anesthesia, medicine.medical_treatment, Extracorporeal membrane oxygenation, Medicine, Extracorporeal cardiopulmonary resuscitation, business
Abstract

The addition of extracorporeal membrane oxygenation (ECMO) to conventional cardiopulmonary resuscitation (CPR), termed extracorporeal cardiopulmonary resuscitation (ECPR), has significantly improved survival in selected patient populations. Despite this advancement, significant neurological impairment persists in approximately half of survivors. ECPR represents a potential advancement for patients who experience refractory cardiac arrest (CA) due to a reversible etiology and do not regain spontaneous circulation. Important risk factors for acute brain injury (ABI) in ECPR include lack of perfusion, reperfusion, and altered cerebral autoregulation. The initial hypoxic-ischemic injury caused by no-flow and low-flow states after CA and during CPR is compounded by reperfusion, hyperoxia during ECMO support, and nonpulsatile blood flow. Additionally, ECPR patients are at risk for Harlequin syndrome with peripheral cannulation, which can lead to preferential perfusion of cerebral vessels with deoxygenated blood. Lastly, the oxygenator membrane is prothrombotic and requires systemic anticoagulation. The two competing phenomena result in thrombus formation, hemolysis, and thrombocytopenia, increasing the risk of ischemic and hemorrhagic ABI. In addition to clinical studies, we assessed available ECPR animal models to identify the mechanisms underlying ABI at the cellular level. Standardized multimodal neurological monitoring may facilitate early detection of and intervention for ABI. With the increasing use of ECPR, it is critical to understand the pathophysiology of ABI, its prevention, and the management strategies for improving the outcomes of ECPR. Translational and clinical research focusing on acute ABI immediately after ECMO cannulation and its short- and long-term neurological outcomes are warranted.

Published
2021

49. Mechanical ventilation in acute brain injury patients with acute respiratory distress syndrome

Author

Mariyam Humayun, Lavienraj Premraj, Vishank Shah, and Sung-Min Cho

Subjects
General Medicine
Abstract

Acute respiratory distress syndrome (ARDS) is commonly seen in patients with acute brain injury (ABI), with prevalence being as high as 35%. These patients often have additional risk factors for ARDS compared to general critical care patients. Lung injury in ABI occurs secondary to catecholamine surge and neuro-inflammatory processes. ARDS patients benefit from lung protective ventilation using low tidal volumes, permissive hypercapnia, high PEEP, and lower PO2 goals. These strategies can often be detrimental in ABI given the risk of brain hypoxia and elevation of intracranial pressure (ICP). While lung protective ventilation is not contraindicated in ABI, special consideration is warranted to make sure it does not interfere with neurological recovery. Permissive hypercapnia with low lung volumes can be utilized in patients without any ICP issues but those with ICP elevations can benefit from continuous ICP monitoring to personalize PCO2 goals. Hypoxia leads to poor outcomes in ABI, hence the ARDSnet protocol of lower PO2 target (55–80 mmHg) might not be the best practice in patients with concomitant ARDS and ABI. High-normal PO2 levels are reasonable in target in severe ABI with ARDS. Studies have shown that PEEP up to 12 mmHg does not cause significant elevations in ICP and is safe to use in ABI though mean arterial pressure, respiratory system compliance, and cerebral perfusion pressure should be closely monitored. Given most trials investigating therapeutics in ARDS have excluded ABI patients, focused research is needed in the field to advance the care of these patients using evidence-based medicine.

Published
2022

50. Challenges in Brain Death Determination in Extracorporeal Membrane Oxygenation – A Single Center Experience

Author

David X Zhao, Giorgio Caturegli, Christopher Wilcox, R. Scott Stephens, Bo Soo Kim, Steven Keller, Romergryko G Geocadin, Glenn JR Whit, and Sung-Min Cho

Abstract

Background Conducting an apnea test (AT) in patients on extracorporeal membrane oxygenation (ECMO) support is challenging, leading to variable approaches for determining brain death (BD), also known as death by neurologic criteria (DNC). This study aims to describe the diagnostic criteria and barriers for DNC in a high-volume ECMO center with an emphasis on the role of AT. Methods A retrospective review of a prospective observational standardized neuromonitoring study was conducted in adult VA- and VV-ECMO patients at a tertiary center from June 2016-March 2022. Brain death was defined according to the 2010American Academy of Neurologyguidelines. AT for DNC in this study was performed in accordance with the 2020 Journal of the American Medical Association BD/DNC criteria recommendations for ECMO patients, including a period of pre-oxygenation, setting ECMO sweep to 0.5-1 L/min, and measuring serial blood gases. Results During the study period, 15 of 300 (5%) patients underwent testing for DNC. Eight (2.7%) ECMO patients (median age = 44 years, 75% male, and 50% VA-ECMO) were diagnosed with BD, six (75%) of whom were determined with AT. In the other two patients who did not undergo AT due to safety concerns, ancillary tests (TCD and EEG) were consistent with BD and the patients were declared BD on the basis of those findings. An additional seven (2.3%) patients (median age = 55 years, 71% male, and 86% VA ECMO) were noted to have absent brainstem reflexes but failed to complete determination of DNC as they underwent withdrawal of life-sustaining treatment due to family wishes before a full evaluation was completed. Six (86%) of these patients with unconfirmed BD had at least one ancillary test performed that were not consistent with BD despite either neurological exam findings and/or AT results supporting a BD diagnosis. In the seventh patient, although absent brainstem reflexes were noted on the neurological exam with explanatory findings on imaging, there was no AT or ancillary testing done. Conclusion AT was used safely and successfully in 6 of the 8 ECMO patients diagnosed with BD, though providers were more confident using AT with ancillary tests. AT was always consistent with the neurological exam and imaging findings suggesting BD. However, there are limitations to ancillary tests for BD assessments when used without AT and we recommend performing at least two ancillary tests to confirm brain death if AT cannot be performed or is inconclusive in ECMO patients.

Published
2022

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