370 results on '"ICU Department"'
Search Results
2. The Difference Between Using Local and General Dexamethasone in Arthroscopic Anterior Cruciate Ligament Repair
- Author
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Mahmoud Sharara, Lecturer of Anesthesiology, Pain, and ICU Department
- Published
- 2024
3. Effect of Prone Positionning in Non Intubated Patients
- Author
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Mhamed Sami Mebazaa, Professor head of Anesthesiology and ICU department
- Published
- 2024
4. Hemidiaphragmatic Paralysis Following Supraclavicular Brachial Plexus Blockade.
- Author
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Abanoub Youssief Mosaad, Resident in Anesthesia and ICU department faculty of medicine, Sohag university
- Published
- 2024
5. Contribution of Ondansetron to Preventing Post-Dural Puncture Headaches Following Spinal Anesthesia (OPDPH)
- Author
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Mhamed Sami Mebazaa, Professor head of anesthesiology and ICU department
- Published
- 2024
6. Buccal Midazolam Versus Intranasal Dexmedetomidine Plus Oral Chloral Hydrate in Inguinal Hernia Repair
- Author
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Ramy Mousa, Anesthesia and surgical ICU department, Faculty of Medicine, Benha University, Egypt
- Published
- 2024
7. Sevoflurane and Intravenous Anesthesia in Hypospadias Repair
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Ramy Mousa, Professor of Anesthesia and surgical ICU department, Faculty of Medicine, Benha University, Egypt
- Published
- 2024
8. Caudal Epidural Prolotherapy Versus Steroids in Failed Back Surgery Syndrome
- Author
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Ahmed Shehab, MD, Lecturer in Anaesthesia and Surgical ICU department
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- 2024
9. Evaluation of the Diaphragm Performance During Weaning From Mechanical Ventilation
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Mhamed Sami Mebazaa, Professor head of anesthesiology and ICU department
- Published
- 2024
10. Prophylaxis Against Postoperative Nausea and Vomiting After Laparoscopic Cholecystectomy
- Author
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yasmine mohammed mahmoud mustafa eldeba, Resident doctor of Anaesthesia and ICU Department
- Published
- 2023
11. Prospective Comparative Study Between Ultrasound-guided Continuous Erector Spinae Plane Block and the Use of Intravenous Patient Controlled Analgesia for Management of Pain in Patients With Multiple Fracture Ribs
- Author
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Ahmed Mahmoud Azmy, assistant lecteurer anaethesia and ICU department sohag univerisity hospital
- Published
- 2023
12. Comparative Study Between The Efficacy Of Quadratus Lumborum Block VS Conventional Analgesia In Patients Undergoing Open Inguinal Hernia Surgical Repair
- Author
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Ahmed Mamdouh Ahmed, Resident doctor at Anesthesia and ICU department
- Published
- 2023
13. Comparative Study Between the Efficacy of The Serratus Anterior Plane Block and Lumbar Intrathecal Fentanyl Injection for Postoperative Analgesia After Modified Radical Mastectomy
- Author
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Ahmed Mohamed Nozahy, resident doctor at anesthesia and ICU department
- Published
- 2023
14. Surgical Site Infiltration Using Ketamine Versus Bupivacaine for Analgesia in Post-operative Appendectomy Operation
- Author
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Gehad Ahmed Aly, resident doctor at Anaesthesia and ICU department sohag university hospital
- Published
- 2022
15. Effect of Dexamethasone as an Adjuvant to Bupivacaine in Bilateral Erector Spinae Block on Postoperative Pain and Diaphragmatic Function After Pediatric Cardiac Surgeries : A Randomized Controlled Clinical Trial
- Author
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Amonios khalil, assistant lecturer at anaesthesia and ICU department
- Published
- 2022
16. Serum Rennin Kinetics Versus Serum Lactate Kinetics as Predictors of Mortality in Septic Shock Patients
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Omar Rabiee Ali, Assistant Lecturer, Anesthesia and ICU department, Faculty of medicine, Assiut University
- Published
- 2022
17. Intrathecal Atropine Versus Intravenous Ondasetron in Post Operative Nausea Due to Intrathecal Morphine
- Author
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Shehab Mahmoud Mohamed, resident doctor at anesthesia and ICU department sohag university hospital
- Published
- 2021
18. Comparative Study Between Caudal Epidural Block and Ultrasound Guided Transversus Abdominis Plane Block for Post Operative Analgesia in Children Undergoing Infraumblical Surgeries
- Author
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Haitham Mohamed Ismail, resident doctor at anesthesia and ICU department
- Published
- 2021
19. Effects of Dexmedetomidine vs Propofol in Patients With Intra-abdominal Sepsis
- Author
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Ibraheem Abdelmageed, assistant lecturer at anaesthesia and ICU department faculty of medicine assiut university
- Published
- 2021
20. Prognostic Value of Lactates in ICU
- Author
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Mhamed Sami Mebazaa, Professor head of ICU department
- Published
- 2021
21. Effect of Rosuvastatin on the Clinical Features of Preeclampsia
- Author
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Sara Mansour, assistant lecturer on anasthesia and icu department
- Published
- 2020
22. NHF vs NIV in Patients With Acute Exacerbation of COPD
- Author
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Venizeleio General Hospital, Heraklion, Crete, Larissa University Hospital, Sotiria General Hospital, and ISCHAKI ELENI, Consultant, ICU Department
- Published
- 2020
23. Inspiratory Muscle Training and Nasal High Flow in Difficult Weaning
- Author
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ISCHAKI ELENI, Consultant, ICU Department
- Published
- 2020
24. Risk Factors and Common Preventive Measures for Ventilator Associated Pneumonia in Patients With Severe Traumatic Brain Injury
- Author
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mohamed mahmoud abdelaziz, specialist at anesthesia and ICU department
- Published
- 2017
25. Efficacy and Safety of Adding Atracurium to Percaruncular Block for High Myopes Undergoing Cataract Surgery
- Author
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Maha Mostafa Ahmad, MD, Assistant Lecturer - Anesthesia, pain management and surgical ICU department
- Published
- 2017
26. Multicenter Study of Iloprost Inhaled in Pulmonary Hypertension After Repair of Congenital Heart Diseases (CHD)
- Author
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Cardiothoracic Surgical Group of Chinese Society of Pediatric Surgery and Xu Zhuoming, Director of ICU, Department of thoracic and cardiovascular surgery, Shanghai Children's Medical Center
- Published
- 2016
27. Prospective Comparison of Primary Abdominal Closure and Vacuum Assisted Laparostomy in Treatment of Severe Peritonitis
- Author
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Zuzana Serclova, MD, Head of ICU - Department of Surgery, Principal Investigator
- Published
- 2012
28. Antibiotic Prophylaxis in the Prevention of Surgical Site Infections After Selected Urgent Abdominal Surgical Procedures
- Author
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Zuzana Serclova, MD, Head of ICU - Department of Surgery, Principal Investigator
- Published
- 2012
29. International retrospective natural history study of LMNA-related congenital muscular dystrophy
- Author
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Gabriele Siciliano, Sonia Messina, David Gómez-Andrés, A. Reghan Foley, Luisa Politano, Pascal Sabouraud, Hirofumi Komaki, Rachel Alvarez, Adele D'Amico, Sandra Donkervoort, Pomi Yun, Vincent Laugel, Gina Norato, Hui Xiong, Lorenzo Maggi, Edmar Zanoteli, Susana Quijano-Roy, Monique M. Ryan, Thomas Voit, Gisèle Bonne, Ulrike Schara, Claudia Castiglioni, Ricardo Erazo-Torricelli, Carsten G. Bönnemann, Karin Kleinsteuber, Rabah Ben Yaou, Chiara Marini-Bettolo, Emmanuelle Lagrue, M. Mayer, Tyler Mark Pierson, Anna Sarkozy, Isabelle Desguerre, Sandra Mercier, Ivana Dabaj, Andrés Nascimento, Marta Bertoli, Nicolas Deconinck, Francesco Muntoni, Liliana Vercelli, Eugenio Mercuri, Akihiko Ishiyama, Soledad Monges, Grace Yoon, Juliana Gurgel-Giannetti, Institut Català de la Salut, [Ben Yaou R] Sorbonne Université, Inserm, Institut de Myologie, Centre de Recherche en Myologie, F-75013 Paris, France. APHP-Sorbonne Université, Neuromuscular Disorders Reference Center of Nord-Est-Île de France, FILNEMUS, ERN-Euro-NMD, Service de Neuromyologie, Institute de Myologie, G.H. Pitié-Salpêtrière Paris F-75013, France. [Yun P, Norato G, Donkervoort S] Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. [Dabaj I] APHP-Université Paris-Saclay, Neuromuscular Disorders Reference Center of Nord-Est-Île de France, FILNEMUS, ERN-Euro-NMD, Pediatric Neurology and ICU Department, DMU Santé Enfant Adolescent (SEA), Raymond Poincaré University Hospital, Garches France. INSERM U 1245, ED497, School of Medicine, Rouen University, Rouen, France. [Xiong H] INSERM U 1245, ED497, School of Medicine, Rouen University, Rouen, France. [Gómez-Andrés D] Servei de Neurologia Pediàtrica (ERN-RND - EURO-NMD), Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
muscular dystrophy ,Pediatrics ,medicine.medical_specialty ,Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins::Nuclear Matrix-Associated Proteins::Lamins::Lamin Type A [CHEMICALS AND DRUGS] ,enfermedades musculoesqueléticas::enfermedades musculares::trastornos musculares atróficos::distrofias musculares [ENFERMEDADES] ,Intellectual and Developmental Disabilities (IDD) ,early onset ,Medizin ,LMNA ,Cardiovascular ,aminoácidos, péptidos y proteínas::proteínas::proteínas nucleares::proteínas asociadas a la matriz nuclear::laminas::lamina de tipo A [COMPUESTOS QUÍMICOS Y DROGAS] ,03 medical and health sciences ,0302 clinical medicine ,Rare Diseases ,Clinical Research ,medicine ,Genetics ,Other subheadings::Other subheadings::/genetics [Other subheadings] ,Muscular dystrophy ,030304 developmental biology ,Pediatric ,Distròfia muscular - Fisiologia patològica ,0303 health sciences ,Distròfia muscular - Aspectes genètics ,business.industry ,Otros calificadores::Otros calificadores::/genética [Otros calificadores] ,laminopathies ,General Engineering ,Musculoskeletal Diseases::Muscular Diseases::Muscular Disorders, Atrophic::Muscular Dystrophies [DISEASES] ,medicine.disease ,Brain Disorders ,Clinical trial ,Natural history ,Other subheadings::Other subheadings::/pathology [Other subheadings] ,Musculoskeletal ,Cohort ,striated muscle ,Congenital muscular dystrophy ,Age of onset ,business ,Otros calificadores::Otros calificadores::/patología [Otros calificadores] ,030217 neurology & neurosurgery ,Natural history study ,4.2 Evaluation of markers and technologies - Abstract
Laminopaties; Distròfia muscular; Múscul estriat Laminopatías; Distrofia muscular; Músculo estriado Laminopathies; Muscular dystrophy; Striated muscle Muscular dystrophies due to heterozygous pathogenic variants in LMNA gene cover a broad spectrum of clinical presentations and severity with an age of onset ranging from the neonatal period to adulthood. The natural history of these conditions is not well defined, particularly in patients with congenital or early onset who arguably present with the highest disease burden. Thus the definition of natural history endpoints along with clinically revelant outcome measures is essential to establishing both clinical care planning and clinical trial readiness for this patient group. We designed a large international cross-sectional retrospective natural history study of patients with genetically proven muscle laminopathy who presented with symptoms before two years of age intending to identify and characterize an optimal clinical trial cohort with pertinent motor, cardiac and respiratory endpoints. Quantitative statistics were used to evaluate associations between LMNA variants and distinct clinical events. The study included 151 patients (median age at symptom onset 0.9 years, range: 0.0–2.0). Age of onset and age of death were significantly lower in patients who never acquired independent ambulation compared to patients who achieved independent ambulation. Most of the patients acquired independent ambulation (n = 101, 66.9%), and subsequently lost this ability (n = 86; 85%). The age of ambulation acquisition (median: 1.2 years, range: 0.8–4.0) and age of ambulation loss (median: 7 years, range: 1.2–38.0) were significantly associated with the age of the first respiratory interventions and the first cardiac symptoms. Respiratory and gastrointestinal interventions occurred during first decade while cardiac interventions occurred later. Genotype–phenotype analysis showed that the most common mutation, p.Arg249Trp (20%), was significantly associated with a more severe disease course. This retrospective natural history study of early onset LMNA-related muscular dystrophy confirms the progressive nature of the disorder, initially involving motor symptoms prior to onset of other symptoms (respiratory, orthopaedic, cardiac and gastrointestinal). The study also identifies subgroups of patients with a range of long-term outcomes. Ambulatory status was an important mean of stratification along with the presence or absence of the p.Arg249Trp mutation. These categorizations will be important for future clinical trial cohorts. Finally, this study furthers our understanding of the progression of early onset LMNA-related muscular dystrophy and provides important insights into the anticipatory care needs of LMNA-related respiratory and cardiac manifestations. This work was supported by the AFM-Telethon, the Institut National de la Santé et de la Recherche Médicale (INSERM) and Sorbonne Université (R.B.Y., G.B.), intramural funds of the National Institute of Neurological Disorders and Stroke, National Institutes of Health (C.G.B.), Cure-CMD (A.R., G.B., R.B.Y.), The Andres Marcio Fondation (G.B., R.B.Y). and the Cedars-Sinai Diana and Steve Marienhoff Fashion Industries Guild Endowed Fellowship in Pediatric Neuromuscular and the Fashion Industries Guild Endowed Fellowship for the Undiagnosed Diseases Program (T.M.P).
- Published
- 2021
30. Clinical pharmacology of exogenously administered alkaline phosphatase
- Author
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J.G. van der Hoeven, Ferdinand T F Snellen, M. Bulitta, Philippe G. Jorens, Jaap E. Tulleken, Peter Pickkers, R. Lins, S. Ramael, Peter Rogiers, J. Meulenbelt, Herbert Spapen, Jan Bakker, Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Department of Intensive Care Medicine (551), Radboud University Medical Center [Nijmegen], Department of Anesthesiology, Isala Klinieken, Department of Intensive Care, Antwerp University Hospital [Edegem] (UZA), Erasmus Medical Centre, Department of Critical Care Medicine and Clinical Pharmacology, Division of Intensive Care Centre, University Medical Centre Utrecht, Institute for Risk Assessment Sciences, Utrecht University, ICU Department, University Hospital, Intensive and Respiratory Care Unit, University Medical Centre, Clinical Pharmacology Unit Antwerp, SGS Life Science Services (SGS), SGS (SGS)-SGS (SGS), and CRM Biometrics GmbH
- Subjects
Adult ,Male ,EXPRESSION ,medicine.medical_specialty ,Renal failure ,Time Factors ,Pharmacology ,Loading dose ,law.invention ,Sepsis ,Pharmacokinetics ,Double-Blind Method ,law ,PHOSPHODIESTERASE ACTIVITY ,Internal medicine ,Intensive care ,Alkaline phosphatase ,medicine ,Humans ,Pharmacology (medical) ,Infusions, Intravenous ,Volunteer ,ComputingMilieux_MISCELLANEOUS ,Aged ,Inflammation ,Clinical pharmacology ,SEPSIS ,business.industry ,Tumor Necrosis Factor-alpha ,Pharmacology. Therapy ,Interleukins ,SEPTIC SHOCK ,General Medicine ,Middle Aged ,medicine.disease ,ADENOSINE ,Endotoxemia ,Pathogenesis and modulation of inflammation [N4i 1] ,Clinical trial ,Endocrinology ,Pharmacodynamics ,Female ,business ,Half-Life - Abstract
Contains fulltext : 79632.pdf (Publisher’s version ) (Closed access) PURPOSE: To evaluate the clinical pharmacology of exogenous alkaline phosphatase (AP). METHODS: Randomized, double-blind, placebo-controlled sequential protocols of (1) ascending doses and infusion duration (volunteers) and (2) fixed dose and duration (patients) were conducted at clinical pharmacology and intensive care units. A total of 103 subjects (67 male volunteers and 36 patients with severe sepsis) were administered exogenous, 10-min IV infusions (three ascending doses) or 24-72 h continuous (132.5-200 U kg(-1) 24 h(-1)) IV infusion with/without preceding loading dose and experimental endotoxemia for evaluations of pharmacokinetics, pharmacodynamics, safety parameters, antigenicity, inflammatory markers, and outcomes. RESULTS: Linearity and dose-proportionality were shown during 10-min infusions. The relatively short elimination half-life necessitated a loading dose to achieve stable enzyme levels. Pharmacokinetic parameters in volunteers and patients were similar. Innate immunity response was not significantly influenced by AP, while renal function significantly improved in sepsis patients. CONCLUSIONS: The pharmacokinetics of exogenous AP is linear, dose-proportional, exhibit a short half-life, and are not influenced by renal impairment or dialysis.
- Published
- 2009
31. Acceptability, validity and responsiveness of inertial measurement units for assessing motor recovery after gene therapy in infants with early onset spinal muscular atrophy: a prospective cohort study.
- Author
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Barrois R, Tervil B, Cacioppo M, Barnerias C, Deladrière E, Leloup-Germa V, Hervé A, Oudre L, Ricard D, Vidal PP, Vayatis N, Roy SQ, Brochard S, Gitiaux C, and Desguerre I
- Subjects
- Humans, Infant, Male, Female, Prospective Studies, Pilot Projects, Muscular Atrophy, Spinal diagnosis, Muscular Atrophy, Spinal physiopathology, Reproducibility of Results, Recovery of Function, Cohort Studies, Spinal Muscular Atrophies of Childhood diagnosis, Spinal Muscular Atrophies of Childhood rehabilitation, Spinal Muscular Atrophies of Childhood therapy, Spinal Muscular Atrophies of Childhood physiopathology, Accelerometry instrumentation, Genetic Therapy methods
- Abstract
Background: Onasemnogene abeparvovec gene replacement therapy (GT) has changed the prognosis of patients with spinal muscular atrophy (SMA) with variable outcome regarding motor development in symptomatic patients. This pilot study evaluates acceptability, validity and clinical relevance of Inertial Measurement Units (IMU) to monitor spontaneous movement recovery in early onset SMA patients after GT., Methods: Clinical assessments including CHOPINTEND score (the gold standard motor score for infants with SMA) and IMU measurements were performed before (M0) and repeatedly after GT. Inertial data was recorded during a 25-min spontaneous movement task, the child lying on the back, without (10 min) and with a playset (15 min) wearing IMUs. Two commonly used parameters, norm acceleration 95th centile (||A||_95) and counts per minute (||A||_CPM) were computed for each wrist, elbow and foot sensors., Results: 23 SMA-patients were included (mean age at diagnosis 8 months [min 2, max 20], 19 SMA type 1, three type 2 and one presymptomatic) and 104 IMU-measurements were performed, all well accepted by families and 84/104 with a good child participation (evaluated with Brazelton scale). ||A||_95 and ||A||_CPM showed high internal consistency (without versus with a playset) with interclass correlation coefficient for the wrist sensors of 0.88 and 0.85 respectively and for the foot sensors of 0.93 and 0.91 respectively. ||A||_95 and ||A||_CPM were strongly correlated with CHOPINTEND (r for wrist sensors 0.74 and 0.67 respectively and for foot sensors 0.61 and 0.68 respectively, p-values < 0.001). ||A||_95 for the foot, the wrist, the elbow sensors and ||A||_CPM for the foot, the wrist, the elbow sensors increased significantly between baseline and the 12 months follow-up visit (respective p-values: 0.004, < 0.001, < 0.001, 0.006, < 0.001, < 0.001)., Conclusion: IMUs were well accepted, consistent, concurrently valid, responsive and associated with unaided sitting acquisition especially for the elbow sensors. This study is the first reporting a large set of inertial sensor derived data after GT in SMA patients and paves the way for IMU-based follow-up of SMA patients after treatment., (© 2024. The Author(s).)
- Published
- 2024
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32. Diagnostic value of syndecan-1 for coronary artery lesions and correlation analysis of laboratory indicators in Kawasaki disease patients.
- Author
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Dai L, Zhang L, He J, Huang R, Tang W, Guo H, and Shang X
- Subjects
- Humans, Male, Female, Child, Preschool, Retrospective Studies, Infant, Case-Control Studies, Child, ROC Curve, Syndecan-1 blood, Mucocutaneous Lymph Node Syndrome blood, Mucocutaneous Lymph Node Syndrome diagnosis, Coronary Artery Disease blood, Coronary Artery Disease diagnosis, Biomarkers blood
- Abstract
Background: To explore the application value of syndecan-1 (SDC-1) in the diagnosis of coronary artery lesions (CALs) in Kawasaki disease (KD) patients and the correlation of multiple laboratory indicators in KD patients., Methods: 86 pediatric Kawasaki disease (KD) patients and 52 healthy controls admitted from January 2018 to December 2023 were retrospectively analyzed. Venous blood samples from KD patients were analyzed for white blood cells (WBC), platelets (PLT), C-reactive protein (CRP), interleukin-6 (IL-6), syndecan-1 (SDC-1), coagulation parameters, and lipid profiles. Correlations between these laboratory indicators were assessed. Receiver operating characteristic (ROC) curve analysis determined the diagnostic value of SDC-1 for coronary artery lesions (CALs) in KD patients. SDC-1 levels were further compared across different CAL severity groups., Results: The levels of ALT, AST, WBC, PLT, CRP, IL-6, and SDC-1 in the KD group were significantly higher than those in the control group (P < 0.05). Coagulation function analysis showed that APTT, TT and FIB levels were significantly increased in the KD group compared with the control group (P < 0.05). Lipid profile analysis revealed that TC, HDL-C, and ApoA1 were significantly decreased, whereas TG, LDL-C, and ApoB100 were significantly increased in the KD group (P < 0.05). Refractory KD patients exhibited significantly higher levels of ALT, AST, SDC-1, CRP, WBC, and TG compared to responsive KD patients (P < 0.05). Correlation analysis indicated a strong positive correlation between PLT and LDL-C (r = 0.227, P = 0.035) and between IL-6 and TG (r = 0.491, P = 0.000), while CRP was negatively correlated with ApoA1 (r = -0.265, P = 0.014). Among the 86 KD patients, 41 (47.67%) developed CALs, with 19 classified as mild, 15 as moderate, and 7 as severe. For predicting CALs among KD patients, the threshold of SDC-1 was identified as 5.5 ng/ml, with a sensitivity of 70.7%, specificity of 64.4%, positive predictive value of 65.91%, negative predictive value of 69.05%, and an AUC of 0.762 (95% confidence interval 0.662-0.861, P < 0.001). SDC-1 levels significantly differed among the CAL severity groups (P = 0.008), with higher levels observed in moderate compared to mild CALs, and in severe compared to moderate CALs., Conclusion: In conclusion, SDC-1 has strong clinical value in the diagnosis of CALs in KD patients, and there is a close relationship between the levels of inflammatory factors, coagulation function and lipid levels in KD patients., (© 2024. The Author(s).)
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- 2024
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33. Proteomic basis for pancreatic acinar cell carcinoma and pancreatoblastoma as similar yet distinct entities.
- Author
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Tanaka A, Ogawa M, Zhou Y, Hendrickson RC, Miele MM, Li Z, Klimstra DS, Wang JY, and Roehrl MHA
- Abstract
Acinar cell carcinoma (ACC) and pancreatoblastoma (PBL) are rare pancreatic malignancies with acinar differentiation. Proteogenomic profiling of ACC and PBL revealed distinct protein expression patterns compared to pancreatic ductal adenocarcinoma (PDAC) and benign pancreas. ACC and PBL exhibited similarities, with enrichment in proteins related to RNA processing, chromosome organization, and the mitoribosome, while PDACs overexpressed proteins associated with actin-based processes, extracellular matrix, and immune-active stroma. Pathway activity differences in metabolic adaptation, epithelial-to-mesenchymal transition, and DNA repair were characterized between these diseases. PBL showed upregulation of Wnt-CTNNB1 and IGF2 pathways. Seventeen ACC-specific proteins suggested connections to metabolic diseases with mitochondrial dysfunction, while 34 PBL-specific proteins marked this pediatric cancer with an embryonic stem cell phenotype and alterations in chromosomal proteins and the cell cycle. This study provides novel insights into the proteomic landscapes of ACC and PBL, offering potential targets for diagnostic and therapeutic development., (© 2024. The Author(s).)
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- 2024
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34. Cardiac Paraganglioma in a Young Patient Presents with Angina-like Symptoms: A Case Report and Literature Review.
- Author
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Alnahar BW, Almiqlash B, Hassanain H, Al-Najjar E, Esmail A, Zainab A, and Ratnani I
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- Humans, Young Adult, Male, Echocardiography, Fatal Outcome, Angina Pectoris etiology, Angina Pectoris surgery, Paraganglioma surgery, Paraganglioma complications, Paraganglioma diagnosis, Heart Neoplasms surgery, Heart Neoplasms complications, Heart Neoplasms diagnosis
- Abstract
Paragangliomas are rare extra-adrenal neuroendocrine tumors originating from chromaffin tissue that present a diagnostic and therapeutic challenge due to their diverse clinical manifestations and low incidence. While these tumors often manifest as catecholamine-secreting functional tumors, their clinical presentation can vary, leading to delayed diagnosis and challenging management. This study presents the case of a 22-year-old patient with cardiac paraganglioma who initially presented with angina-like symptoms, highlighting the importance of considering this rare condition in young individuals with nonspecific complaints. Diagnostic imaging, including transthoracic echocardiography, CT angiography, and MRI, played a crucial role in identifying the tumor's location and vascularization. Surgical excision, including pulmonary artery graft and CABG, was the primary management approach, which was accompanied by intraoperative complications that later led to CCU admission, followed by postoperative complications, ultimately leading to the patient's death. This case highlights the significance of early recognition and management of complications following a surgical approach to treat paragangliomas.
- Published
- 2024
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35. Real-world multidisciplinary outcomes of onasemnogene abeparvovec monotherapy in patients with spinal muscular atrophy type 1: experience of the French cohort in the first three years of treatment.
- Author
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Desguerre I, Barrois R, Audic F, Barnerias C, Chabrol B, Davion JB, Durigneux J, Espil-Taris C, Gomez-Garcia de la Banda M, Guichard M, Isapof A, Nougues MC, Laugel V, Le Goff L, Mercier S, Pervillé A, Richelme C, Thibaud M, Sarret C, Schweitzer C, Testard H, Trommsdorff V, Vanhulle C, Walther-Louvier U, Altuzarra C, Chouchane M, Ropars J, Quijano-Roy S, and Cances C
- Subjects
- Humans, Female, Male, Infant, Biological Products therapeutic use, France, Cohort Studies, Genetic Therapy, Treatment Outcome, Prospective Studies, Recombinant Fusion Proteins, Spinal Muscular Atrophies of Childhood drug therapy, Spinal Muscular Atrophies of Childhood therapy
- Abstract
Background: Spinal muscular atrophy type 1 (SMA1) is the most severe and early form of SMA, a genetic disease with motor neuron degeneration. Onasemnogene abeparvovec gene transfer therapy (GT) has changed the natural history of SMA1, but real-world data are scarce., Methods: A French national expert committee identified 95 newly diagnosed treatment-naive SMA1 patients between June 2019 and June 2022. We prospectively report on children treated with GT as the first and only therapy who had more than one-year of follow-up., Results: Forty-six SMA1 patients received GT. Twelve patients received other treatments. Patients with respiratory insufficiency were oriented toward palliative care after discussion with families. Twenty-nine of the treated patients with more than 12 months of follow-up were included in the follow-up analysis. Among them, 17 had 24 months of follow-up. The mean age at treatment was 7.5 (2.1-12.5) months. Twenty-two patients had two SMN2 copies, and seven had three copies. One infant died in the month following GT due to severe thrombotic microangiopathy, and another died due to respiratory distress. Among the 17 patients with 24 months of follow-up, 90% required spinal bracing (15/17), three patients required nocturnal noninvasive ventilation, and two needed gastrostomy. Concerning motor milestones at the 24-month follow-up, all patients held their head, 15/17 sat for 30 s unassisted, and 12/17 stood with aid. Motor scores (CHOPINTEND and HINE-2) and thoracic circumference significantly improved in all patients., Conclusions: Our study shows favorable motor outcomes and preserved respiratory and feeding functions in treatment-naive SMA1 infants treated by GT as the first and only therapy before respiratory and bulbar dysfunctions occurred. Nevertheless, almost all patients developed spinal deformities., (© 2024. The Author(s).)
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- 2024
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36. Clinical Outcomes of Angiotensin II Therapy in Vasoplegic Shock: A Systematic Review and Meta-Analysis.
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Alamami A, Rahhal A, Alqudah B, Shebani A, Alammora A, Mohammad H, Omar AS, and Shehatta AL
- Abstract
Background: Angiotensin II is a peptide hormone vasopressor that activates angiotensin type 1 (AT1) receptors leading to vasoconstriction, the augmentation of arterial blood pressure (ABP), and organ perfusion. Angiotensin II was found to increase the ABP in catecholamine-refractory vasodilatory shock. Whether this effect improves the chances of survival or not remains inconclusive. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of angiotensin II in vasoplegic shock., Objectives: To evaluate the clinical significance of angiotensin II effects in vasoplegic shock concerning the hemodynamic impact, mortality outcomes, and side effects., Methods: Following PRISMA guidelines, we searched PubMed and EMBASE for experimental and observational studies published in English exploring the clinical outcomes of angiotensin II use in vasodilatory shock till 1 July 2024. Two independent authors assessed the quality and risk of bias of the included studies. A random effect model (Mantel-Haenszel) was used to combine data. The primary outcome was in-hospital mortality associated with angiotensin II use in comparison to standard therapy, while the secondary outcomes were mean arterial pressure (MAP) change, multi-organ failure (MOF), and the incidence of atrial fibrillation (AF). The Q test and I
2 were used to examine heterogeneity, with I2 > 50% indicating marked heterogeneity., Results: A total of eight studies ( n = 974) comparing angiotensin II to standard therapy in vasoplegic shock were included in the systematic review, with three studies comprising 461 patients included in the final analysis of the primary outcome. Only one study evaluated the use of angiotensin II as a primary vasopressor, while the rest reported angiotensin II use in catecholamine-refractory vasodilatory shock. Overall, angiotensin II use was associated with similar in-hospital mortality compared to standard therapy (risk ratio [RR] = 0.83; 95% CI, 0.68-1.02, I2 = 0%). Likewise, there was no difference in MOF and AF (MOF: RR = 1.01; 95% CI, 0.61-1.65, I2 = 0%; AF: RR = 1.27; 95% CI, 0.38-4.23, I2 = 5%). However, angiotensin II use demonstrated a significant MAP increase (mean difference = -9.60; 95% CI, -9.71, -9.49, I2 = 0%)., Conclusions: In vasodilatory shock, angiotensin II use demonstrated comparable in-hospital mortality compared to standard therapy. Nevertheless, it resulted in significant MAP change, which may encourage clinicians to use it in cases of profound hypotension.- Published
- 2024
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37. Takotsubo Syndrome: Differences between Peripartum Period and General Population.
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Tzerefos S, Aloizou D, Nikolakopoulou S, and Aloizos S
- Abstract
Takotsubo syndrome (TTS) was first described in postmenopausal women with transient regional wall motion abnormalities. The trigger is usually an emotional or physical stress. The catecholamine hypothesis seems to be the most prevailing. The main difference between TTS and acute coronary syndromes is that there is no obstructive coronary disease to explain the regional abnormalities. In this form, the left ventricle resembles the fishing jar which is used to trap octopus in Japan. However, to date more atypical forms are recognized. Also, the syndrome is not limited to older women. Nowadays, TTS is presented even in pregnancy and postpartum females. Our experience revealed cases of patients during these periods and some of them suffered from reverse Takotsubo. Additionally, the initial diagnosis in some patients was other than TTS. Due to these findings, we suggest that this type of TTS is not very rare but underestimated. For this reason, further studies are needed to support and explain this condition.
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- 2024
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38. Multidisciplinary Approach in Atrial Fibrillation: As Good as Gold.
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Lucà F, Abrignani MG, Oliva F, Canale ML, Parrini I, Murrone A, Rao CM, Nesti M, Cornara S, Di Matteo I, Barisone M, Giubilato S, Ceravolo R, Pignalberi C, Geraci G, Riccio C, Gelsomino S, Colivicchi F, Grimaldi M, and Gulizia MM
- Abstract
Atrial fibrillation (AF) represents the most common sustained arrhythmia necessitating dual focus: acute complication management and sustained longitudinal oversight to modulate disease progression and ensure comprehensive patient care over time. AF is a multifaceted disorder; due to such a great number of potential exacerbating conditions, a multidisciplinary team (MDT) should manage AF patients by cooperating with a cardiologist. Effective management of AF patients necessitates the implementation of a well-coordinated and tailored care pathway aimed at delivering optimized treatment through collaboration among various healthcare professionals. Management of AF should be carefully evaluated and mutually agreed upon in consultation with healthcare providers. It is crucial to recognize that treatment may evolve due to the emergence of new risk factors, symptoms, disease progression, and advancements in treatment modalities. In the context of multidisciplinary AF teams, a coordinated approach involves assembling a diverse team tailored to meet individual patients' unique needs based on local services' availability.
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- 2024
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39. High-volume hemofiltration does not protect human kidney endothelial and tubular epithelial cells from septic plasma-induced injury.
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Medica D, Quercia AD, Marengo M, Fanelli V, Castellano G, Fabbrini P, Migliori M, Merlotti G, Camussi G, Joannes-Boyau O, Honorè PM, and Cantaluppi V
- Subjects
- Humans, Male, Acute Kidney Injury therapy, Acute Kidney Injury etiology, Female, Middle Aged, Apoptosis, Aged, Kidney Tubules metabolism, Cytokines metabolism, Cytokines blood, Cell Adhesion, Sepsis therapy, Endothelial Cells metabolism, Hemofiltration methods, Epithelial Cells metabolism
- Abstract
High volume hemofiltration (HVHF) could remove from plasma inflammatory mediators involved in sepsis-associated acute kidney injury (SA-AKI). The IVOIRE trial did not show improvements of outcome and organ dysfunction using HVHF. The aim of this study was to evaluate in vitro the biological effects of plasma of patients treated by HVHF or standard volume hemofiltration (SVHF). We evaluated leukocyte adhesion, apoptosis and functional alterations of endothelial cells (EC) and tubular epithelial cells (TEC). In vitro data were correlated with plasma levels of TNF-α, Fas-Ligand (FasL), CD40-Ligand (CD40L), von Willebrand Factor (vWF) and endothelial-derived microparticles. An experimental model of in vitro hemofiltration using LPS-activated blood was established to assess cytokine mass adsorption during HVHF or SVHF. Plasma concentrations of TNF-ɑ, FasL, CD40L and von Willebrand Factor (vWF) were elevated at the start (d1h0) of both HVHF and SVHF, significantly decreased after 6 h (d1h6), remained stable after 12 h (d1h12) and then newly increased at 48 h (d3h0). Plasma levels of all these molecules were similar between HVHF- and SVHF-treated patients at all time points considered. In addition, the levels of endothelial microparticles remained always elevated, suggesting the presence of a persistent microvascular injury. Plasma from septic patients induced leukocyte adhesion on EC and TEC through up-regulation of adhesion receptors. Moreover, on EC, septic plasma induced a cytotoxic and anti-angiogenic effect. On TEC, septic plasma exerted a direct pro-apoptotic effect via Fas up-regulation and caspase activation, loss of polarity, altered expression of megalin and tight junction molecules with an impaired ability to internalize albumin. The inhibition of plasma-induced cell injury was concomitant to the decrease of TNF-α, Fas-Ligand and CD40-Ligand levels. The protective effect of both HVHF and SVHF was time-limited, since a further increase of circulating mediators and plasma-induced cell injury was observed after 48 h (d3h0). No significant difference of EC/TEC damage were observed using HVHF- or SVHF-treated plasma. The in vitro hemofiltration model confirmed the absence of a significant modulation of cytokine adsorption between HVHF and SVHF. In comparison to SVHF, HVHF did not increase inflammatory cytokine clearance and did not reverse the detrimental effects of septic plasma-induced EC and TEC injury. Further studies using adsorptive membranes are needed to evaluate the potential role of high dose convective therapies in the limitation of the harmful activity of plasma soluble factors involved in SA-AKI.Trial registration IVOIRE randomized clinical trial; ClinicalTrials.gov (NCT00241228) (18/10/2005)., (© 2024. The Author(s).)
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- 2024
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40. Omarigliptin/rosinidin combination ameliorates cyclophosphamide-induced lung toxicity in rats: The interaction between glucagon-like peptide-1, TXNIP/NLRP3 inflammasome signaling, and PI3K/Akt/FoxO1 axis.
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Abd Elmaaboud MA, Kabel AM, Borg HM, Magdy AA, Kabel SM, Arafa EA, Alsufyani SE, and Arab HH
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- Animals, Male, Rats, Lung drug effects, Lung metabolism, Lung pathology, Anthocyanins pharmacology, Oxidative Stress drug effects, Dipeptidyl-Peptidase IV Inhibitors pharmacology, Rats, Wistar, Pyrimidines pharmacology, Lung Injury chemically induced, Lung Injury drug therapy, Lung Injury metabolism, Lung Injury pathology, Forkhead Box Protein O1, Heterocyclic Compounds, 2-Ring, Cyclophosphamide toxicity, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Inflammasomes metabolism, Inflammasomes drug effects, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction drug effects, Phosphatidylinositol 3-Kinases metabolism, Glucagon-Like Peptide 1 metabolism, Pyrans pharmacology
- Abstract
Cyclophosphamide is an anti-neoplastic drug that has shown competence in the management of a broad range of malignant tumors. In addition, it represents a keystone agent for management of immunological conditions. Despite these unique properties, induction of lung toxicity may limit its clinical use. Omarigliptin is one of the dipeptidyl peptidase-4 inhibitors that has proven efficacy in management of diabetes mellitus. Rosinidin is an anthocyanidin flavonoid that exhibited promising results in management of diseases characterized by oxidative stress, inflammation, and apoptosis. The present work investigated the possible effects of omarigliptin with or without rosinidin on cyclophosphamide-induced lung toxicity with an exploration of the molecular mechanisms that contribute to these effects. In a rodent model of cyclophosphamide elicited lung toxicity, the potential efficacy of omarigliptin with or without rosinidin was investigated at both the biochemical and the histopathological levels. Both omarigliptin and rosinidin exhibited a synergistic ability to augment the tissue antioxidant defenses, mitigate the inflammatory pathways, restore glucagon-like peptide-1 levels, modulate high mobility group box 1 (HMGB1)/receptors of advanced glycation end products (RAGE)/nuclear factor kappa B (NF-κB) axis, downregulate the fibrogenic mediators, and create a balance between the pathways involved in apoptosis and the autophagy signals in the pulmonary tissues. In conclusion, omarigliptin/rosinidin combination may be introduced as a novel therapeutic modality that attenuates the different forms of lung toxicities induced by cyclophosphamide., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
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- 2024
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41. Does vitamin D supplementation impact serotonin levels? A systematic review and meta-analysis.
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Alimohammadi-Kamalabadi M, Ziaei S, Hasani M, Mohammadi S, Mehrbod M, Morvaridi M, Persad E, Belančić A, Malekahmadi M, Estêvão MDDMAO, Daneshzad E, and Heshmati J
- Abstract
Background and Aims: Vitamin D deficiency impacts a significant proportion of the world's population, and this deficiency has been linked to various conditions characterized by imbalanced serotonin regulation. The objective of this systematic review and meta-analysis was to evaluate the effect of vitamin D supplementation on serum serotonin levels., Methods: We conducted a comprehensive search of PubMed, Scopus, Cochrane Central for Randomized Clinical Trials, and Web of Science up to September 2022, without any language restrictions. The effect sizes were calculated using the standard mean difference (SMD) and 95% confidence interval (CI)., Results: Six randomized clinical trials involving 356 participants were included in the analysis. Our findings indicated no significant changes in serotonin levels between the intervention and control groups (SMD: 0.24 ng/mL, 95% CI: -0.28, 0.75, p > 0.10). Subgroup analysis also did not reveal any significant changes in serotonin levels among children, participants with autism spectrum disorders, interventions lasting 10 weeks or longer, or those receiving vitamin D doses below 4000 IU/day., Conclusion: Although the results obtained in this systematic review are inconclusive, they support the need for further well-designed randomized trials to assess the potential role of vitamin D supplementation in regulating serotonin levels and potentially ameliorating depression and related disorders., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)
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- 2024
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42. Proteogenomic characterization of pancreatic neuroendocrine tumors uncovers hypoxia and immune signatures in clinically aggressive subtypes.
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Tanaka A, Ogawa M, Zhou Y, Otani Y, Hendrickson RC, Miele MM, Li Z, Klimstra DS, Wang JY, and Roehrl MH
- Abstract
Pancreatic neuroendocrine tumors (PanNETs) represent well-differentiated endocrine neoplasms with variable clinical outcomes. Predicting patient outcomes using the current tumor grading system is challenging. In addition, traditional systemic treatment options for PanNETs, such as somatostatin analogs or cytotoxic chemotherapies, are very limited. To address these issues, we characterized PanNETs using integrated proteogenomics and identified four subtypes. Two proteomic subtypes showed high recurrence rates, suggesting clinical aggressiveness that was missed by current classification. Hypoxia and inflammatory pathways were significantly enriched in the clinically aggressive subtypes. Detailed analyses revealed metabolic adaptation via glycolysis upregulation and oxidative phosphorylation downregulation under hypoxic conditions. Inflammatory signature analysis revealed that immunosuppressive molecules were enriched in immune hot tumors and might be immunotherapy targets. In this study, we characterized clinically aggressive proteomic subtypes of well-differentiated PanNETs and identified candidate therapeutic targets., Competing Interests: D.S.K. is now an employee of Paige.AI. M.H.R. is a member of the Scientific Advisory Boards of Azenta Life Sciences and Universal Diagnostics (UDX). None of these companies had any role in the support, design, execution, data analysis, or any other aspect of this study., (© 2024 Published by Elsevier Inc.)
- Published
- 2024
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43. Strategies to prevent blood loss and reduce transfusion in emergency general surgery, WSES-AAST consensus paper.
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Coccolini F, Shander A, Ceresoli M, Moore E, Tian B, Parini D, Sartelli M, Sakakushev B, Doklestich K, Abu-Zidan F, Horer T, Shelat V, Hardcastle T, Bignami E, Kirkpatrick A, Weber D, Kryvoruchko I, Leppaniemi A, Tan E, Kessel B, Isik A, Cremonini C, Forfori F, Ghiadoni L, Chiarugi M, Ball C, Ottolino P, Hecker A, Mariani D, Melai E, Malbrain M, Agostini V, Podda M, Picetti E, Kluger Y, Rizoli S, Litvin A, Maier R, Beka SG, De Simone B, Bala M, Perez AM, Ordonez C, Bodnaruk Z, Cui Y, Calatayud AP, de Angelis N, Amico F, Pikoulis E, Damaskos D, Coimbra R, Chirica M, Biffl WL, and Catena F
- Subjects
- Humans, Blood Loss, Surgical prevention & control, General Surgery, Acute Care Surgery, Blood Transfusion methods, Consensus
- Abstract
Emergency general surgeons often provide care to severely ill patients requiring surgical interventions and intensive support. One of the primary drivers of morbidity and mortality is perioperative bleeding. In general, when addressing life threatening haemorrhage, blood transfusion can become an essential part of overall resuscitation. However, under all circumstances, indications for blood transfusion must be accurately evaluated. When patients decline blood transfusions, regardless of the reason, surgeons should aim to provide optimal care and respect and accommodate each patient's values and target the best outcome possible given the patient's desires and his/her clinical condition. The aim of this position paper was to perform a review of the existing literature and to provide comprehensive recommendations on organizational, surgical, anaesthetic, and haemostatic strategies that can be used to provide optimal peri-operative blood management, reduce, or avoid blood transfusions and ultimately improve patient outcomes., (© 2024. The Author(s).)
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- 2024
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44. Complex SMN Hybrids Detected in a Cohort of 31 Patients With Spinal Muscular Atrophy.
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Costa-Roger M, Blasco-Pérez L, Gerin L, Codina-Solà M, Leno-Colorado J, Gómez-García De la Banda M, Garcia-Uzquiano R, Saugier-Veber P, Drunat S, Quijano-Roy S, and Tizzano EF
- Abstract
Background and Objectives: Spinal muscular atrophy (SMA) is a recessive neuromuscular disorder caused by the loss or presence of point pathogenic variants in the SMN1 gene. The main positive modifier of the SMA phenotype is the number of copies of the SMN2 gene, a paralog of SMN1 , which only produces around 10%-15% of functional SMN protein. The SMN2 copy number is inversely correlated with phenotype severity; however, discrepancies between the SMA type and the SMN2 copy number have been reported. The presence of SMN2-SMN1 hybrids has been proposed as a possible modifier of SMA disease., Methods: We studied 31 patients with SMA, followed at a single center and molecularly diagnosed by Multiplex Ligand-Dependent Probe Amplification (MLPA), with a specific next-generation sequencing protocol to investigate their SMN2 genes in depth. Hybrid characterization also included bioinformatics haplotype phasing and specific PCRs to resolve each SMN2-SMN1 hybrid structure., Results: We detected SMN2-SMN1 hybrid genes in 45.2% of the patients (14/31), the highest rate reported to date. This represents a total of 25 hybrid alleles, with 9 different structures, of which only 4 are detectable by MLPA. Of particular interest were 2 patients who presented 4 SMN2-SMN1 hybrid copies each and no pure SMN2 copies, an event reported here for the first time. No clear trend between the presence of hybrids and a milder phenotype was observed, although 5 of the patients with hybrid copies showed a better-than-expected phenotype. The higher hybrid detection rate in our cohort may be due to both the methodology applied, which allows an in-depth characterization of the SMN genes and the ethnicity of the patients, mainly of African origin., Discussion: Although hybrid genes have been proposed to be beneficial for patients with SMA, our work revealed great complexity and variability between hybrid structures; therefore, each hybrid structure should be studied independently to determine its contribution to the SMA phenotype. Large-scale studies are needed to gain a better understanding of the function and implications of SMN2-SMN1 hybrid copies, improving genotype-phenotype correlations and prediction of the evolution of patients with SMA., Competing Interests: E.F. Tizzano has served as a consultant and has participated on advisory boards for Novartis Gene Therapies, Inc., Biogen, Biologix, Cytokinetics, Novartis, and Roche, and research funding from Biogen/Ionis and Roche. S. Quijano-Roy is a site principal investigator for clinical trials of Biogen and Novartis Gene Therapies, Inc.; has served as a consultant and has participated on advisory boards for Novartis Gene Therapies, Inc., Biogen, and Roche; and has received travel and speaker honoraria from Biogen, Novartis, and Roche. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
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- 2024
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45. Effect of melatonin supplementation on cardiometabolic risk factors, oxidative stress and hormonal profile in PCOS patients: a systematic review and meta-analysis of randomized clinical trials.
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Ziaei S, Hasani M, Malekahmadi M, Daneshzad E, Kadkhodazadeh K, and Heshmati J
- Subjects
- Humans, Female, Pregnancy, Hormones blood, Antioxidants pharmacology, Antioxidants therapeutic use, Antioxidants administration & dosage, Melatonin pharmacology, Melatonin therapeutic use, Polycystic Ovary Syndrome drug therapy, Polycystic Ovary Syndrome blood, Oxidative Stress drug effects, Cardiometabolic Risk Factors, Randomized Controlled Trials as Topic, Dietary Supplements
- Abstract
Background: To investigate whether melatonin supplementation can enhance cardiometabolic risk factors, reduce oxidative stress, and improve hormonal and pregnancy-related factors in patients with PCOS., Methods: We conducted a systematic search of PubMed/Medline, Scopus, and the Cochrane Library for articles published in English from inception to March 2023. We included randomized controlled trials (RCTs) on the use of melatonin for patients with polycystic ovary syndrome (PCOS). We performed a meta-analysis using a random-effects model and calculated the standardized mean differences (SMDs) and 95% confidence intervals (CIs)., Results: Six studies met the inclusion criteria. The result of meta-analysis indicated that melatonin intake significantly increase TAC levels (SMD: 0.87, 95% CI: 0.46, 1.28, I
2 = 00.00%) and has no effect on FBS, insulin, HOMA-IR, TC, TG, HDL, LDL, MDA, hs-CRP, mFG, SHBG, total testosterone, and pregnancy rate in patients with PCOS compare to controls. The included trials did not report any adverse events., Conclusion: Melatonin is a potential antioxidant that may prevent damage from oxidative stress in patients with PCOS. However, the clear effect of melatonin supplementation on cardiometabolic risk factors, hormonal outcomes, and pregnancy-related outcomes needs to be evaluated further in large populations and long-term RCTs., (© 2024. The Author(s).)- Published
- 2024
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46. Functional benefit of CRISPR-Cas9-induced allele deletion for RYR1 dominant mutation.
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Beaufils M, Melka M, Brocard J, Benoit C, Debbah N, Mamchaoui K, Romero NB, Dalmas-Laurent AF, Quijano-Roy S, Fauré J, Rendu J, and Marty I
- Abstract
More than 700 pathogenic or probably pathogenic variations have been identified in the RYR1 gene causing various myopathies collectively known as " RYR1 -related myopathies." There is no treatment for these myopathies, and gene therapy stands out as one of the most promising approaches. In the context of a dominant form of central core disease due to a RYR1 mutation, we aimed at showing the functional benefit of inactivating specifically the mutated RYR1 allele by guiding CRISPR-Cas9 cleavages onto frequent single-nucleotide polymorphisms (SNPs) segregating on the same chromosome. Whole-genome sequencing was used to pinpoint SNPs localized on the mutant RYR1 allele and identified specific CRISPR-Cas9 guide RNAs. Lentiviruses encoding these guide RNAs and the SpCas9 nuclease were used to transduce immortalized patient myoblasts, inducing the specific deletion of the mutant RYR1 allele. The efficiency of the deletion was assessed at DNA and RNA levels, and at the functional level after monitoring calcium release induced by the stimulation of the RyR1-channel. This study provides in cellulo proof of concept regarding the benefits of mutant RYR1 allele deletion, in the case of a dominant RYR1 mutation, from both a molecular and functional perspective, and could apply potentially to 20% of all patients with a RYR1 mutation., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)
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- 2024
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47. Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study.
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Wozniak H, Tabah A, Barbier F, Ruckly S, Loiodice A, Akova M, Leone M, Conway Morris A, Bassetti M, Arvaniti K, Ferrer R, de Bus L, Paiva JA, Bracht H, Mikstacki A, Alsisi A, Valeanu L, Prazak J, Timsit JF, and Buetti N
- Abstract
Background: Hospital-acquired bloodstream infections are common in the intensive care unit (ICU) and have a high mortality rate. Patients with cirrhosis are especially susceptible to infections, yet there is a knowledge gap in the epidemiological distinctions in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients in the ICU. It has been suggested that cirrhotic patients, present a trend towards more gram-positive infections, and especially enterococcal infections. This study aims to describe epidemiological differences in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients hospitalized in the ICU regarding infection sources, microorganisms and mortality., Methods: Using prospective Eurobact-2 international cohort study data, we compared hospital-acquired bloodstream infections sources and microorganisms in cirrhotic and non-cirrhotic patients. The association between Enterococcus faecium and cirrhosis was studied using a multivariable mixed logistic regression. The association between cirrhosis and mortality was assessed by a multivariable frailty Cox model., Results: Among the 1059 hospital-acquired bloodstream infections patients included from 101 centers, 160 had cirrhosis. Hospital-acquired bloodstream infection source in cirrhotic patients was primarily abdominal (35.6%), while it was pulmonary (18.9%) for non-cirrhotic (p < 0.01). Gram-positive hospital-acquired bloodstream infections accounted for 42.3% in cirrhotic patients compared to 33.2% in non-cirrhotic patients (p = 0.02). Hospital-acquired bloodstream infections in cirrhotic patients were most frequently caused by Klebsiella spp (16.5%), coagulase-negative Staphylococci (13.7%) and E. faecium (11.5%). E. faecium bacteremia was more frequent in cirrhotic patients (11.5% versus 4.5%, p < 0.01). After adjusting for possible confounding factors, cirrhosis was associated with higher E. faecium hospital-acquired bloodstream infections risk (Odds ratio 2.5, 95% CI 1.3-4.5, p < 0.01). Cirrhotic patients had increased mortality compared to non-cirrhotic patients (Hazard Ratio 1.3, 95% CI 1.01-1.7, p = 0.045)., Conclusions: Critically ill cirrhotic patients with hospital-acquired bloodstream infections exhibit distinct epidemiology, with more Gram-positive infections and particularly Enterococcus faecium., (© 2024. The Author(s).)
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- 2024
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48. Predictors and outcomes of withholding and withdrawal of life-sustaining treatments in intensive care units in Singapore: a multicentre observational study.
- Author
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Fong C, Kueh WL, Lew SJW, Ho BCH, Wong YL, Lau YH, Chia YW, Tan HL, Seet YHC, Siow WT, MacLaren G, Agrawal R, Lim TJ, Lim SL, Lim TW, Ho VK, Soh CR, Sewa DW, Loo CM, Khan FA, Tan CK, Gokhale RS, Siau C, Lim NLSH, Yim CF, Venkatachalam J, Venkatesan K, Chia NCH, Liew MF, Li G, Li L, Myat SM, Zena Z, Zhuo S, Yueh LL, Tan CSF, Ma J, Yeo SL, Chan YH, and Phua J
- Abstract
Background: Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches., Methods: This was a multicentre observational study of patients admitted to 21 adult ICUs across 9 public hospitals in Singapore over an average of three months per year from 2014 to 2019. The primary outcome measures were withholding and withdrawal of LST (cardiopulmonary resuscitation, invasive mechanical ventilation, and vasopressors/inotropes). The secondary outcome measure was hospital mortality. Multivariable generalised mixed model analysis was used to identify independent predictors for withdrawal and withholding of LST and if LST limitation predicts hospital mortality., Results: There were 8907 patients and 9723 admissions. Of the former, 80.8% had no limitation of LST, 13.0% had LST withheld, and 6.2% had LST withdrawn. Common independent predictors for withholding and withdrawal were increasing age, absence of chronic kidney dialysis, greater dependence in activities of daily living, cardiopulmonary resuscitation before ICU admission, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and higher level of care in the first 24 h of ICU admission. Additional predictors for withholding included being of Chinese race, the religions of Hinduism and Islam, malignancy, and chronic liver failure. The additional predictor for withdrawal was lower hospital paying class (with greater government subsidy for hospital bills). Hospital mortality in patients without LST limitation, with LST withholding, and with LST withdrawal was 10.6%, 82.1%, and 91.8%, respectively (p < 0.001). Withholding (odds ratio 13.822, 95% confidence interval 9.987-19.132) and withdrawal (odds ratio 38.319, 95% confidence interval 24.351-60.298) were both found to be independent predictors of hospital mortality on multivariable analysis., Conclusions: Differences in the independent predictors of withholding and withdrawal of LST exist. Even after accounting for baseline characteristics, both withholding and withdrawal of LST independently predict hospital mortality. Later mortality in patients who had LST withdrawn compared to withholding suggests that the decision to withdraw may be at the point when medical futility is recognised., (© 2024. The Author(s).)
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- 2024
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49. SEPN1-related myopathy depends on the oxidoreductase ERO1A and is druggable with the chemical chaperone TUDCA.
- Author
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Germani S, Van Ho AT, Cherubini A, Varone E, Chernorudskiy A, Renna GM, Fumagalli S, Gobbi M, Lucchetti J, Bolis M, Guarrera L, Craparotta I, Rastelli G, Piccoli G, de Napoli C, Nogara L, Poggio E, Brini M, Cattaneo A, Bachi A, Simmen T, Calì T, Quijano-Roy S, Boncompagni S, Blaauw B, Ferreiro A, and Zito E
- Subjects
- Humans, Mice, Animals, Taurochenodeoxycholic Acid pharmacology, Oxidoreductases, Mice, Knockout, Muscle Proteins, Muscular Diseases drug therapy, Muscular Diseases genetics, Muscular Diseases metabolism
- Abstract
Selenoprotein N (SEPN1) is a protein of the endoplasmic reticulum (ER) whose inherited defects originate SEPN1-related myopathy (SEPN1-RM). Here, we identify an interaction between SEPN1 and the ER-stress-induced oxidoreductase ERO1A. SEPN1 and ERO1A, both enriched in mitochondria-associated membranes (MAMs), are involved in the redox regulation of proteins. ERO1A depletion in SEPN1 knockout cells restores ER redox, re-equilibrates short-range MAMs, and rescues mitochondrial bioenergetics. ERO1A knockout in a mouse background of SEPN1 loss blunts ER stress and improves multiple MAM functions, including Ca
2+ levels and bioenergetics, thus reversing diaphragmatic weakness. The treatment of SEPN1 knockout mice with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) mirrors the results of ERO1A loss. Importantly, muscle biopsies from patients with SEPN1-RM exhibit ERO1A overexpression, and TUDCA-treated SEPN1-RM patient-derived primary myoblasts show improvement in bioenergetics. These findings point to ERO1A as a biomarker and a viable target for intervention and to TUDCA as a pharmacological treatment for SEPN1-RM., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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50. Outcome measures in Angelman syndrome.
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Hagenaar DA, Bindels-de Heus KGCB, van Gils MM, van den Berg L, Ten Hoopen LW, Affourtit P, Pel JJM, Joosten KFM, Hillegers MHJ, Moll HA, de Wit MY, Dieleman GC, and Mous SE
- Subjects
- Child, Humans, Reproducibility of Results, Body Composition, Plethysmography methods, Electric Impedance, Angelman Syndrome complications, Angelman Syndrome diagnosis
- Abstract
Background: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, little to no expressive speech, visual and motor problems, emotional/behavioral challenges, and a tendency towards hyperphagia and weight gain. The characteristics of AS make it difficult to measure these children's functioning with standard clinical tests. Feasible outcome measures are needed to measure current functioning and change over time, in clinical practice and clinical trials., Aim: Our first aim is to assess the feasibility of several functional tests. We target domains of neurocognitive functioning and physical growth using the following measurement methods: eye-tracking, functional Near-Infrared Spectroscopy (fNIRS), indirect calorimetry, bio-impedance analysis (BIA), and BOD POD (air-displacement plethysmography). Our second aim is to explore the results of the above measures, in order to better understand the AS phenotype., Methods: The study sample consisted of 28 children with AS aged 2-18 years. We defined an outcome measure as feasible when (1) at least 70% of participants successfully finished the measurement and (2) at least 60% of those participants had acceptable data quality. Adaptations to the test procedure and reasons for early termination were noted. Parents rated acceptability and importance and were invited to make recommendations to increase feasibility. The results of the measures were explored., Results: Outcome measures obtained with eye-tracking and BOD POD met the definition of feasibility, while fNIRS, indirect calorimetry, and BIA did not. The most important reasons for early termination of measurements were showing signs of protest, inability to sit still and poor/no calibration (eye-tracking specific). Post-calibration was often applied to obtain valid eye-tracking results. Parents rated the BOD POD als most acceptable and fNIRS as least acceptable for their child. All outcome measures were rated to be important. Exploratory results indicated longer reaction times to high salient visual stimuli (eye-tracking) as well as high body fat percentage (BOD POD)., Conclusions: Eye-tracking and BOD POD are feasible measurement methods for children with AS. Eye-tracking was successfully used to assess visual orienting functions in the current study and (with some practical adaptations) can potentially be used to assess other outcomes as well. BOD POD was successfully used to examine body composition., Trial Registration: Registered d.d. 23-04-2020 under number 'NL8550' in the Dutch Trial Register: https://onderzoekmetmensen.nl/en/trial/23075., (© 2024. The Author(s).)
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- 2024
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