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NAD+associated genes as potential biomarkers for predicting the prognosis of gastric cancer

Oncology Research 2024年第2期32卷 283-296页

作者： XIANGDONG SUN HUIJUAN WEN FAZHAN LI IHTISHAM BUKHARI FEIFEI REN XIA XUE PENGYUAN ZHENG YANG MI Henan Key Laboratory for Helicobacter Pylori&Microbiota and gi Cancer Marshall Medical Research CenterThe Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Gastroenterology The Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and ***,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly *** constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor *** immune checkpoint genes were upregulated in the high-risk *** addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk ***,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk ***,the treatment of NMN showed increased proliferation of AGS and MKN45 *** addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN *** conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.

关键词： NAD+ LncRNAs Cancer Cell infiltration Prognosis Tumor microenvironment

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ICC density predicts bacterial overgrowth in a rat model of post-infectious IBS

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World Journal of Gastroenterology 2010年第29期16卷 3680-3686页

作者： Sam-Ryong Jee Walter Morales Kimberly Low Christopher Chang Amy Zhu Venkata Pokkunuri Soumya Chatterjee Edy Soffer Jeffrey L Conklin Mark Pimentel gi motility program Division of GastroenterologyCedars-Sinai Medical Center

AIM:To investigate the interstitial cells of Cajal(ICC) number using a new rat ***:Sprague-Dawley rats were assigned to two *** first group received gavage with Campylobacter jejuni(***) *** second group was gavaged with *** months after clearance of Campylobacter from the stool,precise segments of duodenum,jejunum,and ileum were ligated in self-contained loops of bowel that were preserved in anaerobic *** muscular plexus ICC(DMP-ICC) were quantified by two blinded readers assessing the tissue in a random,coded *** number of ICC per villus was compared among controls,Campylobacter recovered rats without small intestinal bacterial overgrowth(SIBO),and Campylobacter recovered rats with ***:Three months after recovery,27% of rats gavaged with *** had *** rats with SIBO had a lower number of DMP-ICC than controls in the jejunum and *** there appeared to be a density threshold of 0.12 DMP-ICC/villus that was associated with *** ileal density of DMP-ICC was 0.12(P<0.05).If the density of ICC was < 0.12 DMP-ICC/villus in more than one location of the bowel,88% of these had SIBO compared to 6% in those who did not(P<0.001).CONCLUSION:In this post-infectious rat model,the development of SIBO appears to be associated with a reduction in *** study of this rat model might help understand the pathophysiology of postinfectious irritable bowel syndrome.

关键词： Post-infectious irritable bowel syndrome Bacterial overgrowth Interstitial cells of Cajal Campylobacter

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High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of Genetics and Medicine TIGEMPozzuoliNaples 80131Italy Medical Genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Department of Internal Medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

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Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & Molecular Immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko Hyun Woo Lee Won Joon Oh Hun gi Hong Dinuka Ariyaratne Se Jin Im Tae Jin Kim Department of Immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea Department of Immunology and Molecular Medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka Present address:Immunology and Microbiology Graduate program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous ***,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression ***80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B ***,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after *** of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine ***80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant ***80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B *** transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B *** summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

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Impact of frailty on endoscopic retrograde cholangiopancreatography outcomes in nonagenarians:A United States national experience

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World Journal of Gastrointestinal Endoscopy 2024年第3期16卷 148-156页

作者： Sanket Dhirubhai Basida Dushyant Singh Dahiya Muhammad Nadeem Yousaf Brinda Basida Bhanu Siva Mohan Pinnam Manesh Kumar Gangwani Hassam Ali Sahib Singh Yash R Shah Daksh Ahluwalia Mihir Prakash Shah Saurabh Chandan Neil R Sharma Shyam Thakkar Department of Internal Medicine University of Missouri-ColumbiaColumbiaMO 65212United States Division of Gastroenterology Hepatology&MotilityThe University of Kansas School of MedicineKansas CityKS 66160United States Division of Gastroenterology and Hepatology University of MissouriColumbiaMO 65212United States Department of Rheumatology Medical College of GeorgiaAugusta UniversityNorth AugustaGA 30912United States Department of Internal Medicine John H.Stroger Hospital of Cook CountyChicagoIL 60612United States Department of Internal Medicine The University of ToledoToledoOH 43606United States Division of Gastroenterology and Hepatology East Carolina University/Brody School of MedicineGreenvilleNC 27858United States Department of Internal Medicine Sinai HospitalBaltimoreMD 21215United States Department of Internal Medicine Trinity Health Oakland/Wayne State UniversityPontiacMI 48341United States Division of Gastroenterology and Hepatology Creighton University School of MedicineOmahaNE 68131United States Division of Interventional Oncology&Surgical Endoscopy GI Oncology Tumor Site TeamParkview Cancer InstituteParkview HealthFort WayneIN 46845United States Section of Gastroenterology&Hepatology West Virginia University School of MedicineMorgantownWV 26505United States

BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is an essential therapeutic tool for biliary and pancreatic *** and elderly patients,especially those aged≥90 years are generally considered a higher-risk population for ERCP-related *** To investigate outcomes of ERCP in the Non-agenarian population(≥90 years)concerning *** This is a cohort study using the 2018-2020 National Readmission *** aged≥90 were identified who underwent ERCP,using the international classification of diseases-10 code with clinical *** Hopkins’s adjusted clinical groups frailty indicator was used to classify patients as frail and *** primary outcome was mortality,and the secondary outcomes were morbidity and the 30 d readmission rate related to *** used univariate and multivariate regression models for *** A total of 9448 patients were admitted for any indications of *** and non-frail patients were 3445(36.46%)and 6003(63.53%)*** for ERCP were Choledocholithiasis(74.84%),Biliary pancreatitis(9.19%),Pancreatico-biliary cancer(7.6%),Biliary stricture(4.84%),and Cholangitis(1.51%).Mortality rates were higher in frail group[adjusted odds ratio(aOR)=1.68,P=0.02].The Intra-procedural complications were insigni-ficant between the two groups which included bleeding(aOR=0.72,P=0.67),accidental punctures/lacerations(aOR=0.77,P=0.5),and mechanical ventilation rates(aOR=1.19,P=0.6).Post-ERCP complication rate was similar for bleeding(aOR=0.72,P=0.41)and post-ERCP pancreatitis(aOR=1.4,P=0.44).Frail patients had a longer length of stay(6.7 d vs 5.5 d)and higher mean total charges of hospitalization($78807 vs$71392)compared to controls(P<0.001).The 30 d all-cause readmission rates between frail and non-frail patients were similar(P=0.96).CONCLUSION There was a significantly higher mortality risk and healthcare burden amongst nonagenarian frail patients undergoing ERCP compared

关键词： Endoscopic retrograde cholangiopancreatography Nonagenarians Frailty Mortality Healthcare burden

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Inflammatory bowel disease(ulcerative colitis type)severity shows inverse correlation with semen parameters and testosterone levels

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Asian Journal of Andrology 2024年第2期26卷 155-159页

作者： Darmadi Darmadi Cennikon Pakpahan Rajender Singh Ankur Saharan Wanly Syahrizal Pasaribu Hermansyah Hermansyah Andri Rezano Department of Internal Medicine Faculty of MedicineUniversitas Sumatera UtaraMedan 20155Indonesia Andrology Study program Faculty of MedicineUniversitas AirlanggaSurabaya 60132Indonesia Department of Biomedical Sciences Faculty of MedicineUniversitas AirlanggaSurabaya 60132Indonesia Division of Endocrinology Central Drug Research InstituteLucknowUtar Pradesh 226031India Amity University LucknowUttar Pradesh 226010India Department of Biomedical Sciences Faculty of MedicineUniversitas PadjadjaranSumedang 45363Indonesia

Individuals with inflammatory bowel disease(IBD)have been reported to be at an increased risk of infertility and sexual *** the relationship between them remains unclear,IBD severity is suspected to affect hormone levels and *** analyze the impact of IBD severity on semen parameters and sex hormone levels in ulcerative colitis-type IBD(UC-IBD),we conducted a cross-sectional study involving 120 patients with UC-IBD in Adam Malik General Hospital,Medan,*** patients were classified into three groups based on the Mayo score for Uc,followed by a comparison of various semen and hormone parameters among these *** addition to the cross-sectional analysis,a simple correlation test was conducted irrespective of the patient *** concentration,motility,and morphology were found to decline significantly with an increase in IBD *** classifying patients with IBD into subgroups,the Mayo score showed negative correlations with sperm concentration(r=-0.375,Pmotility(r=-0.660,Pmotility,and morphology declined significantly with the severity of *** study suggests a significant negative impact of IBD severityonsemenqualityand sexhormones.

关键词： inflammatory bowel disease reproductive health sexual health sperm parameter testosterone

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Predicting short-term thromboembolic risk following Roux-en-Y gastric bypass using supervised machine learning

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1097-1108页

作者： Hassam Ali Faisal Inayat Vishali Moond Ahtshamullah Chaudhry Arslan Afzal Zauraiz Anjum Hamza Tahir Muhammad Sajeel Anwar Dushyant Singh Dahiya Muhammad Sohaib Afzal Gul Nawaz Amir H Sohail Muhammad Aziz Department of Gastroenterology East Carolina University Brody School of MedicineGreenvilleNC 27834United States Department of Internal Medicine Allama Iqbal Medical CollegeLahorePunjab 54550Pakistan Department of Internal Medicine Saint Peter's University Hospital and Robert Wood Johnson Medical SchoolNew BrunswickNJ 08901United States Department of Internal Medicine St.Dominic's HospitalJacksonMS 39216United States Department of Internal Medicine Rochester General HospitalRochesterNY 14621United States Department of Internal Medicine Jefferson Einstein HospitalPhiladelphiaPA 19141United States Department of Internal Medicine UHS Wilson Medical CenterJohnsonNY 13790United States Division of Gastroenterology Hepatology and MotilityThe University of Kansas School of MedicineKansasKS 66160United States Department of Internal Medicine Louisiana State University HealthShreveportLA 71103United States Department of Surgery University of New Mexico School of MedicineAlbuquerqueNM 87106United States Department of Gastroenterology and Hepatology The University of ToledoToledoOH 43606United States

BACKGROUND Roux-en-Y gastric bypass(RYGB)is a widely recognized bariatric procedure that is particularly beneficial for patients with class III *** aids in significant weight loss and improves obesity-related medical *** its effectiveness,postoperative care still has *** evidence shows that venous thromboembolism(VTE)is a leading cause of 30-d morbidity and mortality after ***,a clear unmet need exists for a tailored risk assessment tool for VTE in RYGB *** To develop and internally validate a scoring system determining the individualized risk of 30-d VTE in patients undergoing *** Using the 2016–2021 Metabolic and Bariatric Surgery Accreditation Quality Improvement program,data from 6526 patients(body mass index≥40 kg/m^(2))who underwent RYGB were analyzed.A backward elimination multivariate analysis identified predictors of VTE characterized by pulmonary embolism and/or deep venous thrombosis within 30 d of *** resultant risk scores were derived from the coefficients of statistically significant *** performance of the model was evaluated using receiver operating curves through 5-fold *** Of the 26 initial variables,six predictors were *** included a history of chronic obstructive pulmonary disease with a regression coefficient(Coef)of 2.54(P7%(Coef 1.19,P<0.001),venous stasis history(Coef 1.43,P<0.001),and preoperative anticoagulation use(Coef 1.24,P<0.001).These variables were weighted according to their regression coefficients in an algorithm that was generated for the model predicting 30-d VTE risk *** risk model's area under the curve(AUC)was 0.79[95%confidence interval(CI):0.63-0.81],showing good discriminatory power,achieving a sensitivity of 0.60 and a specificity of *** training,the same model performed satisfactorily

关键词： Roux-en-Y gastric bypass Venous thromboembolism Machine learning Bariatric surgery Predictive modeling

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Are bowel symptoms and psychosocial features different in irritable bowel syndrome patients with abdominal discomfort compared to abdominal pain?

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World Journal of Gastroenterology 2022年第33期28卷 4861-4874页

作者： Xiu-Cai Fang Wen-Juan Fan Douglas D Drossman Shao-Mei Han Mei-Yun Ke Department of Gastroenterology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Gastroenterology Tongji HospitalTongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030Hubei ProvinceChina Center of Functional gi and motility Disorders University of North CarolinaChapel HillNC 27517United States Center for Education and Practice of Biopsychosocial Care Drossman GastroenterologyDurhamNC 27713United States Rome Foundation Rome FoundationRaleighNC 27614United States Department of Epidemiology and Statistics Institute of Basic Medical SciencesChinese Academy of Medical Sciences&School of Basic MedicinePeking Union Medical CollegeBeijing 100005China

BACKGROUND The Rome IV criteria eliminated abdominal discomfort for irritable bowel syndrome(IBS), which was previously included in Rome III. There are questions as to whether IBS patients with abdominal discomfort(seen in Rome III but not Rome IV) are different from those with abdominal pain(Rome IV).AIM To compare bowel symptoms and psychosocial features in IBS patients diagnosed with Rome III criteria with abdominal discomfort, abdominal pain, and pain &*** We studied IBS patients meeting Rome III criteria. We administered the IBS symptom questionnaire, psychological status, and IBS quality of life. Patients were classified according to the predominant abdominal symptom associated with defecation into an only pain group, only discomfort group, and pain & discomfort group. We compared bowel symptoms, extraintestinal symptoms, IBS quality of life, psychological status and healthcare-seeking behaviors, and efficacy among the three groups. Finally, we tested risk factors for symptom reporting in IBS *** Of the 367 Rome III IBS patients enrolled, 33.8%(124 cases) failed to meet Rome IV criteria for an IBS diagnosis. There were no meaningful differences between the pain group(n = 233) and the discomfort group(n = 83) for the following:(1) Frequency of defecatory abdominal pain or discomfort;(2) Bowel habits;(3) Coexisting extragastrointestinal pain;(4) Comorbid anxiety and depression;and(5) IBS quality of life scores except more patients in the discomfort group reported mild symptom than the pain group(22.9% vs 9.0%). There is a significant tendency for patients to report their defecatory and non-defecatory abdominal symptom as pain alone, or discomfort alone, or pain & discomfort(all P < 0.001).CONCLUSION IBS patients with abdominal discomfort have similar bowel symptoms and psychosocial features to those with abdominal pain. IBS symptoms manifesting abdominal pain or discomfort may primarily be due to different sensation and reporting expe

关键词： Irritable bowel syndrome Abdominal pain Abdominal discomfort Diagnosis Psychosocial distress Quality of life

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Social learning contributions to the etiology and treatment of functional abdominal pain and inflammatory bowel disease in children and adults

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World Journal of Gastroenterology 2007年第17期13卷 2397-2403页

作者： Rona L Levy Shelby L Langer William E Whitehead School of Social Work University of WashingtonUnited States Center for Functional gi and motility Disorders University-of-North-Carolina-at-Chapel-Hill-United-State

This paper reviews empirical work on cognitive and social learning contributions to the etiology and treatment of illness behavior associated with functional abdominal pain and inflammatory bowel disease. A particular emphasis is placed on randomized controlled trials, the majority of which are multi-modal in orientation, incorporating elements of cognitive behavioral therapy, social learning, and relaxation. Based on this review, we offer methodological and clinical suggestions: (1) Research investigations should include adequate sample sizes, long-term follow-up assessments, and a credible, active control group. (2) Standard gastrointestinal practice should include, when appropriate, learning opportunities for patients and family members, for example, instruction regarding the encouragement of wellness behavior.

关键词：儿童成年人机能性腹痛炎症性肠病病因治疗

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Remimazolam for sedation in gastrointestinal endoscopy:A comprehensive review

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World Journal of Gastrointestinal Endoscopy 2024年第7期16卷 385-395页

作者： Dushyant Singh Dahiya Ganesh Kumar Syeda Parsa Manesh Kumar Gangwani Hassam Ali Amir Humza Sohail Saqr Alsakarneh Umar Hayat Sheza Malik Yash R Shah Bhanu Siva Mohan Pinnam Sahib Singh Islam Mohamed Adishwar Rao Saurabh Chandan Mohammad Al-Haddad Division of Gastroenterology Hepatology&MotilityThe University of Kansas School of MedicineKansas CityMO 66160United States Department of Internal Medicine Chandka Medical CollegeSindh 77280Pakistan Department of Gastroenterology and Hepatology University of Arkansas For Medical SciencesLittle RockAR 72205United States Division of Gastroenterology Hepatology and NutritionEast Carolina University/Brody School of MedicineGreenvilleNC 27858United States Department of Surgery University of New Mexico School of MedicineAlbuquerqueNM 87106United States Department of Internal Medicine University of Missouri-Kansas CityKansas CityMO 64108United States Department of Internal Medicine Geisinger Wyoming Valley Medical CenterWilkes BarrePA 18711United States Department of Internal Medicine Rochester General HospitalRochesterNY 14621United States Department of Internal Medicine Trinity Health Oakland/Wayne State UniversityPontiacMI 48341United States Department of Internal Medicine John H.Stroger Hospital of Cook CountyChicagoIL 60612United States Department of Internal Medicine Sinai hospitalBaltimoreMD 21215United States Department of Hepatology University of MissouriColumbiaMO 65211United States Department of Internal Medicine Guthrie Robert Packer HospitalSayrePA 18840United States Division of Gastroenterology and Hepatology Creighton University School of MedicineOmahaNE 68131United States Division of Gastroenterology and Hepatology Indiana University School of MedicineIndianapolisIN 46202United States

Worldwide,a majority of routine endoscopic procedures are performed under some form of sedation to maximize patient ***,benzodiazepines and opioids continue to be widely ***,in recent years,Remimazolam is gaining immense popularity for procedural sedation in gastrointestinal(gi)*** is an ultra-short-acting benzodiazepine sedative which was approved by the Food and Drug Administration in July 2020 for use in procedural *** has shown a favorable pharmacokinetic and pharmacodynamic profile in terms of its non-specific metabolism by tissue esterase,volume of distribution,total body clearance,and negligible drug-drug *** also has satisfactory efficacy and has achieved high rates of successful sedation in gi ***,studies have demonstrated that the efficacy of Remimazolam is non-inferior to Propofol,which is currently a gold standard for procedural sedation in most parts of the ***,the use of Propofol is associated with hemodynamic instability and respiratory *** contrast,Remimazolam has lower incidence of these adverse effects intra-procedurally and hence,may provide a safer alternative to Propofol in procedural *** this comprehensive narrative review,highlight the pharmacologic characteristics,efficacy,and safety of Remimazolam for procedural *** also discuss the potential of Remimazolam as a suitable alternative and how it can shape the future of procedural sedation in gastroenterology.

关键词： Remimazolam Endoscopy Sedation Outcomes Efficacy Safety Pharmacokinetics

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