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Nguyen Van An,1 Hai Thi Nguyen,2 Van Nguyen Le,1 Ha Thi Thu Van,1 Nguyen Minh Hai,1 Vu Huy Luong,3,4 Vinh Thi Ha Nguyen,4,5 Hoa Quynh Pham,6 Hung Van Le,4,6 Dinh Viet Hung,7 Hoang Trung Kien,8 Minh Nhat Le,9,10 Nguyen Hoang Viet,11 Luong Cong Thuc,12 Ta Ba Thang,13 Tran Viet Tien,14 Le Huy Hoang,15 Nguyen Thuy Tram,15 Tuan Dinh Le,16 Nguyen Tien Son,16 Hai Ha Long Le17,18 1Department of Microbiology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 2Department of Central Laboratory, Bac Ninh Provincial General Hospital, Bac Ninh, Vietnam; 3Department of Laser and Skincare, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 4Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; 5Department of General Planning, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 6Department of Microbiology, Mycology and Parasitology, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 7Department of Psychiatry, Military Medical 103, Vietnam Military Medical University, Hanoi, Vietnam; 8Department of Immunology, Vietnam Military Medical University, Hanoi, Vietnam; 9Tay Nguyen Institute of Science Research, Vietnam Academy of Science and Technology, VAST, Hanoi, Vietnam; 10Antimicrobial Resistance Research Center, National Institute of Infectious Disease, Tokyo, Japan; 11Molecular Pathology Department, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 12Cardiovascular Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 13Respiratory Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 14Department of Infectious Diseases, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 15Department of Bacteriology, National of Hygiene and Epidemiology, Hanoi, Vietnam; 16Department of Rheumatology and Endocrinology, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 17Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 18Department of Biochemistry, Hematology and Immunology, National Hospital of Dermatology and Venereology, Hanoi, VietnamCorrespondence: Hai Ha Long Le, Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, 100000, Vietnam, Tel +84978520055, Email lehalonghai@gmail.comPurpose: Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA) strain, can become resistant to all classes of clinically available antibiotics and causes skin infections and severe infections in the lungs, heart, and bloodstream. The study aimed to evaluate antimicrobial susceptibility patterns and MRSA exhibiting multidrug resistance obtained through a microbiological culture of clinical specimens at Bac Ninh Provincial General Hospital in Bac Ninh Province, Vietnam.Methods: We employed a cross-sectional analysis at Bac Ninh Provincial General Hospital in Vietnam. 15,232 clinical samples from inpatients were examined. S. aureus isolates were identified using established protocols and tested for MRSA and antibiotic susceptibility. Data was analyzed using R software, with statistical calculations to assess associations between variables.Results: Staphylococcus aureus was isolated from 417 samples (2.7%), with 77.2% being MRSA and 22.8% methicillin-susceptible Staphylococcus aureus (MSSA). Significant sources of MRSA were wounds (64.6%) and the surgical unit (50%) according to sample types and hospital wards, respectively. S. aureus showed high resistance rates, the highest being azithromycin (83.2%), and was fully susceptible to vancomycin. Among 294 multidrug-resistant (MDR) strains, the prevalence was 82.0% in MRSA and 18.0% in MSSA.Conclusion: The study highlights widespread antimicrobial resistance among MRSA isolates from a provincial hospital in Vietnam, emphasizing the urgent need for antibiotic surveillance, formulation of antibiotic policies, and preventive measures to tackle the increasing prevalence of multidrug-resistant MRSA.Keywords: Staphylococcus aureus, antibiotic resistance, MRSA, MDR, Vietnam

Oscar Rosenkrantz,1,2 Jannik Wheler,1 Mats Christian Westphal Thrane,3 Lars Pedersen,1 Henrik Toft Sørensen1 1Department of Clinical Epidemiology and Center for Population Medicine, Aarhus University Hospital and Aarhus University, Aarhus, Denmark; 2Department of Anaesthesia, Centre of Head and Orthopaedics, Rigshospitalet, Copenhagen, Denmark; 3Danish Health Data Authority, Copenhagen, DenmarkCorrespondence: Oscar Rosenkrantz, Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Olof Palmes Allé 43, 45, DK, Aarhus N, 8200, Denmark, Tel +45 87 16 72 12, Email oscar.oelrich.rosenkrantz@clin.au.dkBackground: The Danish National Hospital Medication Register (DHMR), one of the first nationwide in-hospital medication registries in the world, contains detailed information on medication administration and dispensing.Objective: To provide an overview of the information recorded in the DHMR and to highlight its strengths and limitations as a pharmacoepidemiological research tool.Methods: We reviewed the registry´s geographic and clinical specialty coverage and medications recorded according to the main groups of the Anatomical Therapeutic Chemical classification system.Results: From May 2018 through December 2023, the DHMR recorded data on more than 1.9 million unique patients from all approximately 50 public hospitals and associated hospital outpatient clinics, totaling 105.3 million recordings of hospital medication use. The registry records detailed data on the indication for medication, medication type, pharmaceutical form, dosage, and administration time, collected through electronic medical record systems. Although the data quality has not yet been evaluated in a scientific context, some potential limitations are known. These include regional differences in the data collection and a lack of data from certain clinical specialties. Due to its recent establishment in 2018, the registered number of patients treated may still be limited for some rarely used medications.Conclusion: The DHMR is an important new resource for research in Denmark. Combined with the Danish National Prescription Registry, which covers all community pharmacies, it offers access to accurate data on medication exposure in the Danish population. Users should be aware of potential issues with lack of information before 2018.Keywords: pharmacoepidemiology, hospital medication system, pharmacotherapy, data source, drug databases, registry data, Denmark

Jakob Kjølby Eika,1,2,* Kasper Bonnesen,1,2,* Lars Pedersen,1,2 Vera Ehrenstein,1,2 Henrik Toft Sørensen,1,2 Morten Schmidt1– 3 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Department of Cardiology, Gødstrup Regional Hospital, Herning, Denmark*These authors contributed equally to this workCorrespondence: Morten Schmidt, Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark and Department of Clinical Medicine, Aarhus University, Olof Palmes Allé 43– 45, Aarhus, 8200, Denmark, Tel +45 87 16 72 12, Email morten.schmidt@clin.au.dkPurpose: Ibuprofen is used to treat acute pericarditis, but high-dose ibuprofen has also been associated with increased cardiovascular risks. We examined the cardiovascular safety of using ibuprofen for acute pericarditis.Patients and Methods: A Danish nationwide, population-based cohort study including patients ≥ 18 years with first-time acute pericarditis (n=12,381) during 1996– 2020 was conducted. Ibuprofen use was modelled in two ways: First, we considered patients exposed based on the tablet strength of their first ibuprofen filling (a proxy for an intention-to-treat analysis). Second, we considered patients exposed in a time-varying manner (a proxy for an as-treated analysis). The primary outcome of major adverse cardiovascular events (MACE) was a composite of myocardial infarction, ischemic stroke, congestive heart failure, and cardiovascular death.Results: In the intention-to-treat analysis, the 1-year risk of MACE was 1.37% (95% confidence interval [CI]: 1.03– 1.79) for ibuprofen initiators and 4.32% (95% CI: 3.89– 4.78) for non-initiators. Compared with non-initiators within 1-year follow-up, the adjusted hazard ratio for MACE was 0.75 (95% CI: 0.67– 0.85) for initiators overall, 0.38 (95% CI: 0.28– 0.52) for initiators of > 400 mg tablets, and 0.87 (95% CI: 0.76– 0.99) for initiators of ≤ 400 mg tablets. In the as-treated analysis, compared with no use, the hazard ratio associated with ibuprofen use was 0.69 (95% CI: 0.54– 0.89) for MACE, 0.82 (95% CI: 0.54– 1.26) for myocardial infarction, 0.74 (95% CI: 0.45– 1.22) for ischemic stroke, 0.67 (95% CI: 0.47– 0.96) for congestive heart failure, and 0.60 (95% CI: 0.31– 1.17) for cardiovascular death.Conclusion: Ibuprofen use for acute pericarditis was not associated with increased cardiovascular risks, supporting its safety in current practice.Keywords: Pericarditis, Anti-Inflammatory Agents, non-steroidal, Cohort Study, Epidemiology

Tian-Yu Yao, Jia-Song Wang, Hua-Tao Xie, Ming-Chang Zhang Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Hua-Tao Xie; Ming-Chang Zhang, Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Tel +86-27-85726662, Email huataoxie@hust.edu.cn; mingc_zhang@hust.edu.cnObjective: To compare differences in postoperative pain, foreign body sensation, photophobia, and lacrimation between balafilcon A and samfilcon A bandage contact lenses (BCLs) in the early stage following pterygium surgery.Methods: A total of 66 eyes with pterygium conjunctival grafts fixed with sutures were included in this study, comprising 32 eyes fixed with samfilcon A and 34 eyes fixed with balafilcon A. Demographic data, postoperative corneal epithelialization time, and subjective discomfort, such as pain (using the visual analog scale [VAS]), were recorded and compared.Results: Significant differences were noted in VAS scores between the first day (P< 0.01) and the second day post-surgery (P=0.03), suggesting that patients experienced less pain after wearing samfilcon A. However, no significant differences were observed in corneal epithelialization time, VAS score before lens removal, foreign body sensation, photophobia, lacrimation, insomnia, and demographic data between the two groups. Finally, only two balafilcon A patients required nonsteroidal analgesics.Conclusion: After pterygium surgery, samfilcon A BCL was associated with lower pain levels compared with balafilcon A BCL and could assist in reducing postoperative discomfort in patients and concurrently improving patient satisfaction.Keywords: bandage contact lenses, pterygium, pain, visual analog scale, samfilcon A, balafilcon A

Bright Etumuse,1 Majesty Greer,2 Jane Onyemachi,1 Youshaa El-Abed,3 Sai Kamma,1 Jay D Shah,4 Henry Tuan Tran,1 Nasir Hussain,5 Thomas P Pittelkow,6 Ryan S D’Souza6 1University of Texas Medical Branch School of Medicine, Galveston, TX, USA; 2Howard University College of Medicine, Washington, DC, USA; 3Kansas City University, Kansas City, MO, USA; 4Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA; 5Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; 6Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USACorrespondence: Ryan S D’Souza, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic 200 First St. SW, Rochester, MN, 55905, USA, Email Dsouza.ryan@mayo.eduBackground: As cannabis legalization expands nationally and globally, its use for chronic pain increases, prompting people to seek information on social media platforms like YouTube. This study evaluates the accuracy and quality of information of popular YouTube videos on cannabis for chronic pain.Methods: Using search terms related to cannabis for pain, the top 66 videos by view count were selected. Each video was classified as useful, misleading, or neither. The quality and reliability of each video were assessed using the modified DISCERN, mDISCERN, score and the Global Quality Scale, GQS. The video characteristics, usefulness classification, mDISCERN scores, and GQS scores were summarized. Continuous and categorical outcomes were compared using t-test and chi-square, respectively.Results: Of the 66 videos, 22.73% (n=15) were classified as useful, and 77.27% (n=51) were classified as neither. Of useful videos, 40.00% (n=6) were uploaded by physicians, 40.00% (n=6) were uploaded by corporations, and 6.67% (n=1) were uploaded by an independent user. Of videos classified as neither useful nor misleading, news sources uploaded 27.45% (n=14) of these videos (P=0.02). Physicians uploaded 37.50% (n = 18) of videos with a GQS score ≥ 3 (P=0.04), while independent users uploaded significantly more videos with a mDISCERN score < 3 (22.20%, P=0.02). Useful videos had a mean GQS of 4.00 ± 0.65 compared to a mean GQS of 2.76 ± 0.86 for videos deemed neither (P< 0.0001).Conclusion: This study suggests a moderate quality of YouTube content on cannabis use for chronic pain. Given cannabis’s growing popularity and potential for misinformation on popular social media platforms, healthcare professionals and organizations should consider uploading educational videos on this topic on YouTube.Keywords: social media, cannabis, medical cannabis, analgesics, YouTube

Shruti Handa,1 Megan R Heffernan,2 Summer Tan,3 David A Keith,1 Annika Rosén,4– 6 Hsinlin Thomas Cheng7 1Division of Oral and Maxillofacial Surgery, Department of Surgery, Massachusetts General Hospital and Harvard School of Dental Medicine, Boston, MA, USA; 2Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; 3Department of Dentistry, Harvard School of Dental Medicine, Boston, MA, USA; 4Department of Oral and Maxillofacial Surgery, Eastman Institute, Stockholm, Sweden; 5Department of Clinical Dentistry, University of Bergen, Bergen, Norway; 6Department of Oral and Maxillofacial Surgery, Haukeland University Hospital, Bergen, Norway; 7Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USACorrespondence: Shruti Handa, Department of Surgery, Massachusetts General Hospital, 165 Cambridge Street, Suite &num;401, Boston, Massachusetts, 02114, USA, Email shanda1@mgh.harvard.eduPurpose: Orofacial Pain (OFP) affects 15% of the general population. OFP conditions can be myofascial, also known as temporomandibular disorders (TMDs) or neuropathic. The underlying pathophysiology in several chronic OFP conditions, is unknown. Small fiber neuropathy (SFN) is a disorder of thinly myelinated A-delta and non-myelinated C-fibers and can manifest as sensory and autonomic neuropathies. SFN has been demonstrated in some OFP conditions. Our study aims to assess the presence of OFP in patients with sensory and autonomic neuropathies and assess the correlation between OFP, skin biopsy and autonomic dysfunction.Patients and Methods: This is a retrospective study (2018– 2020) of patients from the SFN registry, Massachusetts General Hospital, Boston, USA, for the presence of OFP. All patients were included. Primary outcome: Prevalence of OFP in patients with chronic neuropathies. Secondary outcomes: Correlation between OFP and skin biopsy, dysautonomia, headaches, chronic nociceptive pain, psychological conditions, and patient factors, such as mean age and BMI.Results: Charts of 450 patients with sensory and autonomic neuropathies were reviewed. 22.67% (n=102) had OFP. The mean (range) age at biopsy in patients with OFP was 48.36 (20– 81) years, female: male ratio 3.25:1. More OFP patients had negative skin biopsy results (p value< 0.05) than those with sensory neuropathies. Patients with OFP had significantly higher prevalence of psychological conditions (p value 0.000), and higher BMI > 30 (p value 0.025). Dysautonomia was significantly higher in patients with TMDs when compared to the ones without TMDs (p value 0.030). There was no significant difference in mean age, gender predilection, presence of headaches, peripheral neuropathies, and nociceptive pain between patients with and without OFP.Conclusion: OFP and sensory neuropathies can be overlapping conditions. Patients presenting with concomitant TMD and dysautonomia can be further tested for SFN. This can further help us understand a correlation if any, between idiopathic TMD/OFP conditions and SFN and further our understanding of the pathophysiology of these conditions.Keywords: idiopathic facial pain, orofacial pain, temporomandibular disorders, skin biopsy, autonomic dysfunction, sensory neuropathic pain, dysautonomia, small fiber neuropathy

Addyson E Sand,1 Tyler E Powell,1 Helen T Marry,1 Heather R Rathbun,1 Jenna R Steege,1 Allison LeMahieu,2 Adam K Jacob,1 Ryan S D’Souza,1 Oludare O Olatoye1 1Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; 2Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USACorrespondence: Oludare O Olatoye, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA, Email Olatoye.Oludare@mayo.eduBackground: Patients receiving methadone, buprenorphine, and naltrexone for either chronic pain or substance use disorder (SUD) pose perioperative challenges. Due to their complex pharmacology, perioperative recommendations continue to evolve. Deviations from these recommendations may result in worse perioperative outcomes. A formal preoperative evaluation (POE) and optimization of patients on these medications are recommended to address these concerns.Methods: A single-center retrospective electronic health record review was performed with adult patients on methadone, buprenorphine, and naltrexone undergoing elective surgery between January 1, 2010 and December 31, 2020. The primary outcome of interest was the percentage of patients referred to the POE clinic for evaluation prior to the scheduled elective surgery. In addition, we assessed differences in variables (perioperative opioid, hospital length of stay, perioperative multimodal analgesics, perioperative complications, inpatient pain service consult, readmission within 30 days, cancellation of surgery, addiction medicine consult) based on POE clinic evaluation. This analysis was performed separately for patients prescribed these medications for SUD versus chronic pain. Continuous outcomes were analyzed using linear regression with generalized estimating equations (GEE) and robust variance estimates.Results: A total of 714 patients were included in the final analysis, of which 572 (80%) took buprenorphine, methadone, or naltrexone for chronic pain and 142 (20%) took these medications for SUD. Within the chronic pain and SUD subpopulations, 193 (34%) and 35 (25%) patients had formal POE clinic assessments, respectively. Among those taking these medications for chronic pain, POE clinic evaluation was associated with a higher likelihood for receiving non-opioid multimodal analgesics perioperatively (p = 0.016).Conclusion: Formal preoperative evaluations are currently underutilized in patients who take buprenorphine, methadone, or naltrexone for chronic pain or SUD. These patients may benefit from POE clinic assessment to optimize perioperative outcomes.Keywords: preoperative evaluation, chronic opioid therapy, substance use disorder, naltrexone, buprenorphine, methadone, perioperative pain management

Dong-Mei Guan,1,&ast; Yuan-Zhuang Shan,1,&ast; Hao-Tian Zhao,2 Ying Meng,2 Zhong-Rui Yan,2 Hai-Lin Zhang2 1Shandong University of Tradition Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Department of Neurology, Jining No.1 People’s Hospital, Jining, Shandong, People’s Republic of China&ast;These authors contributed equally to this studyCorrespondence: Hai-Lin Zhang, Department of Neurology, Jining No.1 People’s Hospital, No. 6 of Healthy Road, Rencheng District, Jining, Shandong, 272000, People’s Republic of China, Tel +86 176 6130 0365, Email zhanghailin_zhl@126.comBackground: Hemiplegic migraine, a less common variant of migraine, is the focus of this paper. Within the scope of this study, we present a case of hemiplegic migraine that bears the potential for misdiagnosis, particularly as encephalitis.Brief introduction to the Disease: The patient developed a right-sided headache a day prior to admission, accompanied by fever, nausea, vomiting, and left-sided limb weakness. On the fourth day, the patient experienced a grand mal epilepsy, marked by unconsciousness, leftward deviation of both eyes, limb convulsions, and foaming at the mouth. Cerebrospinal fluid analysis revealed no apparent abnormalities, Electroencephalography showed abnormal slow waves, imaging studies indicated swelling and meningeal thickening in the right cortex, and genetic testing identified a heterozygous mutation in the ATPIA2 gene. The diagnosis was hemiplegic migraine, and the patient received symptomatic supportive treatment, leading to improvement and subsequent discharge. Flunarizine and sodium valproate were prescribed post-discharge, and the patient achieved complete recovery after a one-month follow-up.Conclusion: Apart from experiencing headaches, patients with hemiplegic migraine may exhibit additional symptoms like fever, epilepsy, and hemiplegia. These manifestations warrant clinical attention, and if deemed necessary, genetic testing should be conducted, and this is an autosomal dominant pattern.Keywords: ATP1A2 gene mutation, encephalitis, migraine, hemiplegic migraine, swelling of the cortex

Frederik PB Kristensen,1 Sia K Nicolaisen,1 Jens S Nielsen,2,3 Diana H Christensen,1,4 Kurt Højlund,2,3 Henning Beck-Nielsen,2 Jørgen Rungby,5 Søren G Friborg,6 Ivan Brandslund,7,8 Jens S Christiansen4 ,† Peter Vestergaard,9,10 Niels Jessen,11– 13 Michael H Olsen,14,15 Mette K Andersen,16 Torben Hansen,16 Charlotte Brøns,5 Allan Vaag,5,17 Reimar W Thomsen,1 Henrik T Sørensen1 1Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark; 2Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark; 3Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 4Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 5Steno Diabetes Center Copenhagen, Herlev, Denmark; 6Department of Endocrinology, Odense University Hospital, Odense, Denmark; 7Department of Biochemistry, Lillebaelt Hospital, Vejle, Denmark; 8Regional Health Research, University of Southern Denmark, Odense, Denmark; 9Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark; 10Steno Diabetes Center North Denmark, Aalborg, Denmark; 11Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; 12Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark; 13Department of Biomedicine, Aarhus University, Aarhus, Denmark; 14Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 15Department of Internal Medicine and Steno Diabetes Center Zealand, Holbæk Hospital, Holbæk, Denmark; 16Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark; 17Lund University Diabetes Centre, Lund University, Malmö, Sweden†Dr Jens S Christiansen passed away on 16 December 2015Correspondence: Frederik PB Kristensen, Department of Clinical Epidemiology, Aarhus University, Olof Palmes Alle 43-45, Aarhus N, 8200, Denmark, Tel +45 87 16 82 37, Email fpk@clin.au.dkPurpose: This paper provides an overview of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort and biobank, including baseline characteristics of participants enrolled up to 2023, and post-enrollment rates of cardiovascular disease outcomes and mortality.Methods: Since 2010, the DD2 project has enrolled individuals with type 2 diabetes mellitus (T2DM) recently diagnosed by general practitioners and by hospital-based clinicians across Denmark. Data from questionnaires, clinical examinations, and biological samples are collected at enrollment. Additional baseline and longitudinal follow-up data are accessed via linkage to health registries.Results: Between 2010 and 2023, the DD2 project enrolled 11,369 participants (41.3% women, median age 61.4 years). Median T2DM duration at enrollment was 1.3 years, and median BMI was 31.6 kg/m2 for women and 30.5 kg/m2 for men. 18.3% were smokers, 5.7% consumed more than 14/21 units of alcohol weekly (women/men), and 17.9% reported leisure-time physical inactivity. Original midwife records dating back > 80 years revealed that 20.2% of cohort participants had birth weights < 3000 g. Based on complete hospital contact history 10 years before enrollment, 20.7% of cohort participants had macrovascular complications, 17.0% had microvascular complications, and 21.7% had kidney disease based on eGFR or urine albumin-creatinine measurements. At enrollment, statins were used by 68.2%, antihypertensive drugs by 69.9%, and glucose-lowering drugs by 86.5% of individuals. Median HbA1c was 48 mmol/mol and median LDL cholesterol 2.2 mmol/L. Genome-wide genotyping and biomarker data have been analyzed for over 9000 individuals. During the current follow-up time from the enrollment date (median 7.9 years), incident cardiovascular disease rate has been 13.8 per 1000 person-years and the mortality rate has been 17.6 per 1000 person-years.Conclusion: The DD2 cohort, with its detailed information and long-term follow up, can improve our understanding of the progression and prevention of complications among individuals with newly diagnosed T2DM.Keywords: cohort profile, type 2 diabetes mellitus, patient characteristics, Denmark

Wei-Li Xia,1,&ast; Xiao-Hui Zhao,2,&ast; Yuan Guo,1 Hong-Tao Hu,1 Hai-Liang Li1 1Department of Interventional Radiology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China; 2Department of Interventional Radiology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, 300060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hai-Liang Li, Department of interventional radiology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, 127 Dongming Road, Zhengzhou, Henan Province, 450008, People’s Republic of China, Tel +86 13903861969, Fax +0371 65587181, Email lihailianggy@163.comBackground and Objectives: Transarterial chemoembolization (TACE) and 125I seed implantation are methods used to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), PVTT often associated with arterioportal shunts(APS), there are few reports on the combined use of TACE and 125I seed implantation for such patients. This study aimed to evaluate the efficacy and safety of TACE combined with PVTT 125I seed implantation in the treatment of HCC patients with APS.Methods: Forty-two patients diagnosed with HCC combined with PVTT and APS between January 2020 and December 2021 were included. Appropriate materials were selected to transarterial embolization of the APS, and 125I seeds were implanted into the PVTT. The occlusion effect was observed and recorded after 3 months, the efficacy of intrahepatic lesions and PVTT was evaluated, and the patient survival, prognostic factors affecting APS recanalization were analyzed.Results: All 42 patients completed the follow-up three months after treatment. The immediate APS improvement rate was 100%, and the APS improvement rate at the three-month follow-up was 64.29%. The disease control rates of PVTT and intrahepatic lesions were 81.00% and 78.60%, respectively. The patients’ 6-month and 12-month survival rates were 78.6% and 46.8%. The median OS for all patients was 11.90 months, and the median OS was 13.30 months in the APS effective treatment group and 8.30 months in the ineffective group. The PVTT type is the only independent factor affecting APS recanalization. (P=0.02).Conclusion: For HCC patients with PVTT and APS, TACE combine with 125I seed implantation in PVTT is a potentially effective and safe method that contributes to prolonging patient survival.Keywords: hepatocellular carcinoma, transarterial chemoembolization, portal vein tumor thrombus, 125I seed, arterioportal shunts

Dexter Tadiwanashe Chiveto,1,2 Cuthbert Musarurwa,3 Herbert T Mapira,3 Farayi Kaseke,4 Tawanda Nyengerai,5 Timothy Kaseke,6 Elizabeth Gori7 1Department of Laboratory Diagnostic and Investigative Sciences - Chemical Pathology Unit, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe; 2Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; 3Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda; 4Department of Physiotherapy, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda; 5The Best Health Solutions, Johannesburg, Gauteng, South Africa; 6Zimbabwe Aids Prevention Project, ZAPP, Harare, Zimbabwe; 7Department of Medical Biochemistry, Molecular Biology and Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye, RwandaCorrespondence: Elizabeth Gori, Department of Medical Biochemistry, Molecular Biology & Genetics, College of Medicine and Health Sciences-School of Medicine and Pharmacy, University of Rwanda, P.O. Box 117-Butare, Huye, Rwanda, Tel +250 7920 47482, Email e.gori@ur.ac.rwPurpose: Type 2 diabetes mellitus (T2DM) frequently presents with modified cardiometabolic risk profiles, indicative of an elevated susceptibility to cardiovascular disease (CVD). Cardiometabolic risk factors such as obesity, hyperglycemia, hypertension, insulin resistance and dyslipidemia are known contributors to increased CVD hazard in individuals with T2DM. This study evaluated the glycemic control-based cardiometabolic risk profiles of black Zimbabweans with T2DM.Patients and Methods: A cross-sectional study of 116 T2DM patients recruited from diabetic clinics at Parirenyatwa and Sally Mugabe Hospitals, Harare, Zimbabwe, was conducted. Blood samples were collected for glycated hemoglobin (HbA1c) and lipid profile assessment. The Framingham risk scores (FRS) based on body mass index (BMI) and lipid profile were used to determine CVD risk. Parametric variables were analyzed using one-way analysis of variance (ANOVA) with post hoc Bonferroni correction, while non-parametric variables were compared using the Kruskal–Wallis test with post hoc Dunn test for multiple comparisons.Results: The overall frequency of dyslipidemia was 83.6% (n=97) and hypoalphalipoproteinemia was the most prevalent dyslipidemia (79.3%). Median HDLC levels were significantly lower in participants with poor glycemic control (1.12 mmol/L) compared to those with good glycemic control group (1.37 mmol/L) (p=0.011). Despite lack of significant variations in Framingham Risk Scores, there was a trend towards lower FRS-BMI in the good control group (29.8%) compared to the inadequate control (35.4%) and poor control (32.7%) groups (p=0.078).Conclusion: Duration since DM diagnosis was observed to be an important risk factor for poor glycemic control being significantly shorter in those with good glycemic control compared to those with inadequate and poor control. Overall, there was no significant difference in HbA1c status by age but individuals with poor glycemic control were significantly older than those with good control. The most prevalent dyslipidemia among the study participants was hypoalphalipoproteinemia which is reportedly associated with genetic predisposition, warranting further investigations.Keywords: glycated hemoglobin, dyslipidemia, hypoalphalipoproteinemia, Framingham risk score

Nguyen Van An,1,&ast; Hoang Trung Kien,2,&ast; Le Huy Hoang,3 Nguyen Hung Cuong,1 Hoang Xuan Quang,1 Tuan Dinh Le,4 Ta Ba Thang,5 Tien Tran Viet,6 Luong Cong Thuc,7 Dinh Viet Hung,8 Nguyen Hoang Viet,9 Le Nhat Minh,10,11 Vu Huy Luong,12,13 Vinh Thi Ha Nguyen,13,14 Pham Quynh Hoa,15 Hai Ha Long Le16,17 1Department of Microbiology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 2Department of Immunology, Vietnam Military Medical University, Hanoi, Vietnam; 3Department of Bacteriology, National of Hygiene and Epidemiology, Hanoi, Vietnam; 4Department of Rheumatology and Endocrinology, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 5Respiratory Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 6Department of Infectious Diseases, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 7Cardiovascular Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 8Department of Psychiatry, Military Medical 103, Vietnam Military Medical University, Hanoi, Vietnam; 9Molecular Pathology Department, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 10Antimicrobial Resistance Research Center, National Institute of Infectious Disease, NIID, Tokyo, Japan; 11Tay Nguyen Institute of Science Research, Vietnam Academy of Science and Technology, VAST, Hanoi, Vietnam; 12Department of Laser and Skincare, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 13Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; 14Department of General Planning, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 15Department of Microbiology, Mycology and Parasitology, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 16Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 17Department of Biochemistry, Hematology and Immunology, National Hospital of Dermatology and Venereology, Hanoi, Vietnam&ast;These authors contributed equally to this workCorrespondence: Hai Ha Long Le, Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, 100000, Vietnam, Tel +84 978520055, Email lehalonghai@hmu.edu.vnPurpose: At a teaching Hospital in Vietnam, the persistently high incidence of diagnosed wound infection poses ongoing challenges to treatment. This study seeks to explore the causative agents of wound infection and their antimicrobial and multidrug resistance patterns.Methods: A cross-sectional study was conducted at the Department of Microbiology, Military Hospital 103, Vietnam. Data on microorganisms that caused wound infection and their antimicrobial resistance patterns was recorded from hospitalized patients from 2014 to 2021. Using the chi-square test, we analyzed the initial isolation from wound infection specimens collected from individual patients.Results: Over a third (34.9%) of wound infection samples yielded bacterial cultures. Staphylococcus aureus was the most prevalent bacteria, followed by Pseudomonas aeruginosa. Worryingly high resistance rates were observed for several antibiotics, particularly among Gram-negative bacteria. Ampicillin displayed the highest resistance (91.9%), while colistin and ertapenem remained the most effective. In Gram-positive bacteria, glycopeptides like teicoplanin and vancomycin (0% and 3.3% resistance, respectively) were most effective, but their use was limited. Clindamycin and tetracycline showed decreasing effectiveness. Resistance rates differed between surgical and non-surgical wards, highlighting the complex dynamics of antimicrobial resistance within hospitals. Multidrug resistance (MDR) was substantial, with Gram-negative bacteria exhibiting a 63.6% MDR rate. Acinetobacter baumannii showed the highest MDR rate (88.0%).Conclusion: This study investigated wound infection characteristics, antibiotic resistance patterns of common bacteria, and variations by hospital ward. S. aureus was the most prevalent bacteria, and concerning resistance rates were observed, particularly among Gram-negative bacteria. These findings highlight the prevalence of multidrug resistance in wound infections, emphasizing the importance of infection control measures and judicious antibiotic use.Keywords: wound infection, multidrug resistance, antimicrobial resistance, AMR in Vietnam

Jin-yu Shi,1,* Ting-ting Li,1,2,* Hui-ting Yang,1 Shi Zhang,2 Ran An,2 Liang Mao,2 Yang Li,2 Qian Li,2 Guang-yi Luan,2 Yan Shen,2 En-long Wang,2 Guang-hui Liu1,2 1First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang-hui Liu, First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, No. 33, Beiling Street, Huanggu District, Shenyang, Liaoning, 110032, People’s Republic of China, Email guanghui04-09@163.comObjective: This study aimed to investigate the features and underlying principles of acupuncture points used in the treatment of headaches associated with blood stasis syndrome.Methods: Literature on the treatment of blood stasis headache with acupuncture and moxibustion was searched across three Chinese databases and one English database from January 1st, 2000, to January 1st, 2024. Relevant data including titles, journals, authors, keywords, interventions, main acupoints, and outcomes were extracted for further analysis.Results: A total of 112 papers with 102 complete prescriptions were analyzed. Of the 77 acupoints examined, 72 were meridian points, and 5 were extraordinary points, used 699 times in total. The top ten acupoints by frequency were Fengchi (GB20), Taiyang (EX-HN5), Baihui (GV20), Hegu (LI4), Shuaigu (GB8), Taichong (LR3), Xuehai (SP10), Touwei (ST8), Geshu (BL17), and Waiguan (TE5). Yang meridian points were used more frequently than Yin meridian points (82.8% vs 17.2%), with the Gallbladder Meridian of Foot Shaoyang being the most common. Nearly half of the acupoints (49.9%) were on the head and neck, and 23.1% on the lower limbs. Specific acupoints accounted for 53.5% of the total frequency. Fengchi (GB20) and Taiyang (EX-HN5) showed the highest correlation. Association rule mining highlighted combinations like Fengchi (GB20) with Taiyang (EX-HN5) and Baihui (GV20). Cluster analysis yielded five clusters.Conclusion: The study provides insights into selecting effective acupoints and combinations for clinical acupuncture practice and experimental studies in treating blood stasis headaches. Acupoints like Fengchi (GB20), Taiyang (EX-HN5), and Baihui (GV20) may be effective for clinical treatment, but further studies are needed to validate their efficacy.Keywords: headache, blood stasis syndrome, acupuncture, treatment rule, data mining

Niels Obel,1,2 Matthew P Fox,3 Malte M Tetens,2 Lars Pedersen,4 Tyra Grove Krause,5 Henrik Ullum,5 Henrik Toft Sørensen4 1Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, 2300, Denmark; 2Department of Infectious Diseases, Copenhagen University Hospital – Rigshospitalet, Copenhagen, 2100, Denmark; 3Departments of Epidemiology and Global Health, School of Public Health, Boston University, Boston, MA, USA; 4Department of Clinical Epidemiology, Aarhus University, Aarhus N, 8200, Denmark; 5Statens Serum Institut, Copenhagen, 2300, DenmarkCorrespondence: Niels Obel, Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Artillerivej 5, Copenhagen, 2300, Denmark, Tel +4532683252, Email niob@ssi.dkBackground: Observational studies of SARS-CoV-2 vaccine effectiveness are prone to confounding, which can be illustrated using negative control methods.Methods: Nationwide population-based cohort study including two cohorts of Danish residents 60– 90 years of age matched 1:1 on age and sex: A vaccinated and a non-vaccinated cohort, including 61052 SARS-CoV-2 vaccinated individuals between 1 March and 1 July 2021 and 61052 individuals not vaccinated preceding 1 July 2021. From these two cohorts, we constructed negative control cohorts of individuals diagnosed with SARS-CoV-2 infection or acute myocardial infarction, stroke, cancer, low energy fracture, or head-trauma. Outcomes were SARS-CoV-2 infection, negative control outcomes (eg, mammography, prostate biopsy, operation for cataract, malignant melanoma, examination of eye and ear), and death. We used Cox regression to calculate adjusted incidence and mortality rate ratios (aIRR and aMRR).Results: Risks of SARS-CoV2 infection and all negative control outcomes were elevated in the vaccinated population, ranging from an aIRR of 1.15 (95% CI: 1.09– 1.21) for eye examinations to 3.05 (95% CI: 2.24– 4.14) for malignant melanoma. Conversely, the risk of death in the SARS-CoV-2 infected cohort and in all negative control cohorts was lower in vaccinated individuals, ranging from an aMRR of 0.23 (95% CI: 0.19– 0.26) after SARS-CoV-2 infection to 0.50 (95% CI: 0.37– 0.67) after stroke.Conclusion: Our findings indicate that observational studies of SARS-CoV-2 vaccine effectiveness may be subject to substantial confounding. Therefore, randomized trials are essential to establish vaccine efficacy after the emergence of new SARS-CoV-2 variants and the rollout of multiple booster vaccines.Plain Language Summary: Why was this study done: After the emergence of new SARS-CoV-2 variants and the rollout of multiple booster SARS-CoV-2 vaccines, the impact of vaccination on risk of SARS-CoV-2 infection and death after the infection has mainly been explored in observational studies. We used negative control methods to investigate whether confounding affects the results of observational SARS-CoV-2 vaccine effectiveness studies.Findings: We used Danish registry data obtained during the SARS-CoV-2 vaccine roll-out to conduct a nationwide, matched population-based cohort study of Danish residents 60– 90 years in which we compared vaccinated individuals with non-vaccinated individuals. Compared with unvaccinated individuals, vaccinated individuals had increased risks of SARS-CoV2 infection but also had increased risks of all negative control outcomes (mammography, prostate biopsy, operation for cataract, malignant melanoma, examination of eye and ear). The risk of death after SARS-CoV2 infection was lower in the vaccinated cohort, as was the risk of death after acute myocardial infarction, stroke, cancer, low energy fracture, and head-trauma.Meaning: The negative control methods indicate that observational studies of SARS-CoV-2 vaccine effectiveness may be prone to substantial confounding which may impact the observed associations. This bias may both lead to underestimation of vaccine effectiveness (increased risk of SARS-CoV2 infection among vaccinated individuals) and overestimation of the vaccine effectiveness (decreased risk of death after of SARS-CoV2 infection among vaccinated individuals). Our results highlight the need for randomized vaccine efficacy studies after the emergence of new SARS-CoV-2 variants and the rollout of multiple booster vaccines.Keywords: COVID-19, vaccines, cohort studies, bias, confounding factors, epidemiologic

Huong Tu Lam,1 Thang Dinh Nguyen,2 Hoang Huu Bui,1 Thong Duy Vo1,3 1Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Department of Gastroenterology, Cho Ray Hospital, Ho Chi Minh City, Vietnam; 3Department of Gastroenterology, University Medical Center Ho Chi Minh City, Ho Chi Minh City, VietnamCorrespondence: Thong Duy Vo, Department of Gastroenterology, University Medical Center Ho Chi Minh City, 215 Hong Bang, Ward 11, Dis. 5, Ho Chi Minh City, 72714, Vietnam, Tel +84 932039888, Email thong.vd@umc.edu.vnIntroduction: The Charlson Comorbidity Index ≥ 2, in-Hospital onset, Albumin < 2.5 g/dL, altered Mental status, Eastern Cooperative Oncology Group Performance status ≥ 2, Steroid use (CHAMPS) score is a novel and promising prognostic tool. We present an initial external validation of the CHAMPS score for predicting mortality in acute nonvariceal upper gastrointestinal bleeding (NVUGIB) across multiple clinical outcomes.Methods: A prospective cohort study was conducted on adult patients with NVUGIB admitted to the Department of Gastroenterology between November 2022 and June 2023. The CHAMPS score performance in predicting in-hospital outcomes was evaluated by employing area under the receiver operating characteristic (AUROC) curves, followed by a comparative analysis with five pre-existing scores.Results: A total of 140 patients were included in the study. The CHAMPS score showed its highest performance in predicting mortality rates (AUROC = 0.89), significantly outperforming the Glasgow-Blatchford Bleeding Score (GBS) as well as the Albumin level < 3.0 mg/dL, International normalized ratio > 1.5, altered Mental status, Systolic blood pressure ≤ 90 mmHg, and age > 65 years (AIMS65) score (AUROC = 0.72 and 0.71, respectively; all p < 0.05). Subgroup analysis for bleeding-related and non-bleeding-related mortality further confirmed the robust predictive capability of the CHAMPS score (AUROC = 0.88 and 0.87, respectively). The CHAMPS score failed to predict rebleeding and intervention reliably, exhibiting AUROC values of 0.43 and 0.55, respectively. The optimal CHAMPS score cutoff value for predicting mortality was 3 points, achieving 100% sensitivity and 71.2% specificity. In the low-risk category defined by both CHAMPS and GBS scores, mortality and rebleeding rates were 0%. However, within the CHAMPS score-based low-risk group, 58.8% required intervention, contrasting with a 0% intervention rate for the GBS score-based low-risk group (GBS score ≤ 1).Conclusion: The CHAMPS score consistently demonstrated a robust predictive performance for mortality (AUROC > 0.8), facilitating the identification of high-risk patients requiring aggressive treatment and low-risk patients in need of localized treatment or safe discharge after successful bleeding control.Keywords: non-variceal upper gastrointestinal bleeding, CHAMPS, mortality prediction, risk scores, GBS

Runjie Li,1,2,&ast; Rongna Lian,1,3,&ast; Hiruni T Siriwardena,4 Jiaojiao Jiang,5 Ming Yang1,3 1National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Geriatrics, Ya ‘an People’s Hospital, Ya ‘an, People’s Republic of China; 3Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China; 5Rehabilitation Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Yang, Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, Sichuan, People’s Republic of China, Tel\Fax +86 28 8542 2321, Email yangmier@gmail.com; yangmier@scu.edu.cn Jiaojiao Jiang, Rehabilitation Center, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, Sichuan, People’s Republic of China, Tel\Fax +86 28 8542 2313, Email jiangjiaojiao1997@163.comAbstract: Despite over 30 years of microbiome and skeletal muscle research, no quantitative analysis of sarcopenia and the microbiome literature had been conducted. Our bibliometric study examined research status, hotspots, and future trends. We utilized bibliometric techniques to search the Science Citation Index Extended Database on February 27, 2023, using the Bibliometrix package in R to create a map displaying scientific production and subject categories. Collaborative network maps between countries/regions were visualized using Scimago Graphica, while VOSviewer explored collaboration modes among individuals and institutions. We analyzed the top 25 emerging keywords, top co-occurring keyword networks, and co-occurring keyword clusters using CiteSpace. A total of 997 articles were retrieved for sarcopenia and microbiome, of which 633 papers were analyzed. Both the number of publications and total citation frequency had been continuously increasing. The United States had the highest total citation frequency, while China had the highest number of publications. Research on the impact of the microbiome on sarcopenia was in its nascent stage and spans multiple disciplines, including nutrition, microbiology, geriatrics, immunology, endocrinology and metabolism, molecular biology, and sports medicine. The University of Copenhagen contributed the most to the number of publications (n=16), with Tibbett M (n=7) and Hulver MW (n=7) among the top authors. The most published journal was “Nutrients” (n=24). Analysis of keywords and clusters revealed new research hotspots in microbes and sarcopenia, such as malnutrition, dietary fiber, signaling pathways, frailty, and intestinal permeability. Research on the impact of the microbiome on sarcopenia is in its infancy and spans multiple disciplines. Malnutrition, dietary fiber, signaling pathways, frailty, and intestinal microbes are currently research hotspots. Furthermore, the visual atlas analysis of research on microbes and sarcopenia helps to track the knowledge structure in research fields related to sarcopenia and microbes, providing direction for future research. Keywords: bibliometric analysis, microbes, skeletal muscle, scientometrics, muscle wasting

Yu Chen Xu,1,&ast; Qiu Qin Wang,1,&ast; Meng Yuan Chen,1 Yu Jie Gao,1 Jia Yi Wang,1 Hao Tian Ge,1 Heng Weng,1 Ju Ping Chen,2 Gui Hua Xu1 1School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Department of Neurology, Changshu Hospital of Traditional Chinese Medicine, Suzhou, 215500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gui Hua Xu, School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email 7115@njucm.edu.cn Ju Ping Chen, Department of Neurology, Changshu Hospital of Traditional Chinese Medicine, Suzhou, 215500, People’s Republic of China, Email 1523515573@qq.comPurpose: Pain is a common yet undertreated symptom of Parkinson’s disease (PD). This study investigated the effect of Gua Sha therapy on pain in patients with PD.Patients and Methods: A total of 56 PD patients with pain were randomized into either the experimental group (n=28), receiving 12 sessions of Gua Sha therapy, or the control group (n=28) without additional treatment. Participants underwent assessment at baseline, after the twelfth invention, and at the 2-month follow-up timepoints. The primary outcome was KPPS and VAS. Secondary outcomes included UPDRS I–III, PDSS-2, HADS, PDQ-39, and blood biomarkers (5-HT, IL-8, IL-10).Results: The experimental group reported a significant improvement in pain severity, motor functions, affective disorder, and sleep quality (P < 0.05). Furthermore, increasing trends in both 5-HT and IL-10, as well as decreasing trends in IL-8 were observed. No serious adverse events occurred.Conclusion: The preliminary findings suggest that Gua Sha therapy may be effective and safe for alleviating pain and improving other disease-related symptoms in PD patients.Keywords: Parkinson’s disease, pain, Gua Sha therapy, randomized controlled trial

Huan Thanh Nguyen,1,2 Huong Thanh Do,2 Hai Van Be Nguyen,2 Tan Van Nguyen1,3 1Department of Geriatrics and Gerontology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Department of Cardiology, Thong Nhat Hospital, Ho Chi Minh City, Vietnam; 3Department of Interventional Cardiology, Thong Nhat Hospital, Ho Chi Minh City, VietnamCorrespondence: Huan Thanh Nguyen, Department of Geriatrics and Gerontology University of Medicine and Pharmacy at Ho Chi Minh City, 17 Hong Bang Street, Ward 11, District 5, Ho Chi Minh City, Vietnam, Tel +84-909097849, Email huannguyen@ump.edu.vnPurpose: To investigate the prevalence and factors associated with frailty and impact of frailty on hospitalization due to any cause in elderly patients with chronic coronary syndrome (CCS).Patients and Methods: We conducted a study wherein we assessed frailty using Fried frailty phenotype for outpatients aged ≥ 60 years with CCS. Logistic regression analysis was performed to assess the factors associated with frailty. Frailty was adjusted for demographic and geriatric variables and comorbidities to assess its impact on hospitalization.Results: Overall, 420 patients (median age 70 years [interquartile range, 65– 77]; men, 74.5%) who completed the 3-month follow-up period were analyzed. Coronary revascularization for > 1 year was the most common clinical scenario for CCS (59.8%; n = 251). The prevalence of non-frail, pre-frail, and frail patients were 22.4% (n = 94), 49.7% (n = 209), and 27.9% (n = 117), respectively. In the adjusted model, three factors associated with frailty were age ≥ 75 years (odds ratio [OR] 2.29, 95% confidence interval [CI] 1.39– 3.75, P = 0.001), limitations in instrumental activity of daily living (OR 3.89, 95% CI 2.33– 6.48, P < 0.001), and heart failure (OR 2.30, 95% CI 1.32– 4.02, P = 0.003). The overall 3-month hospitalization rate was higher in frail patients than in non-frail patients (23.9% vs 13.5%, P = 0.012). Frailty was associated with hospitalization (OR 1.85, 95% CI 1.04– 3.30, P = 0.037) but in a weak strength of association (r = 0.126).Conclusion: The prevalence of frailty was 27.9% in the elderly patients with CCS. Age ≥ 75 years, limitations in functional status, and heart failure were associated with increased odds of frailty. Frailty was a predictor of 3-month all-cause hospitalization in these patients.Keywords: frailty, chronic coronary syndrome, elderly

Jonas F Ludvigsson,1 Johan Askling,1 Sven Cnattingius,1 Per Hall,1 Lars Klareskog,1 Olof Nyren,1 John A Baron,2 Henrik Toft Sørensen3 1Karolinska Institutet, Solna, Sweden; 2University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 3Aarhus University, Aarhus, DenmarkCorrespondence: Jonas F Ludvigsson, Email jonasludvigsson@yahoo.com

Kuo-Feng Hua,1,2,&ast; Hsien-Ta Hsu,3,4,&ast; May-Shu Huang,5,6 Hsiao-Wen Chiu,1 Wei-Ting Wong,1 Chien-Hsiu Peng,1 Yu-Bei Lin,1 Ann Chen,7 Chien-Chun Wang,8,9 Chung-Hua Hsu,10,11 Chun-Hsien Wu,12 Wen-Yu Lin,1,12 Chen-Lung Ho,13 Lan-Hui Li14 1Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan; 2Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; 3Division of Neurosurgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 4School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan; 5Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 6Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 7Department of Pathology, Hualien Tzu Chi Hospital, Hualien, Taiwan; 8Infectious Disease Division, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan; 9Kunming Prevention and Control Center, Taipei City Hospital, Taipei, Taiwan; 10Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan; 11Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 12Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 13Division of Wood Cellulose, Taiwan Forestry Research Institute, Taipei, Taiwan; 14Department of Laboratory Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan&ast;These authors contributed equally to this workCorrespondence: Lan-Hui Li, Department of Laboratory Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, 100, Kunming Street, Wanhua District, Taipei City, 108203, Taiwan, Tel +886-2-23703739 &num; 1438, Fax +886-2-23885259, Email A1525@tpech.gov.twPurpose: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, crucial in infectious and inflammatory diseases by regulating IL-1β, presents a target for disease management. Neisseria gonorrhoeae causes gonorrhea in over 87 million people annually, with previous research revealing NLRP3 inflammasome activation in infected macrophages. No natural products have been reported to counteract this activation. Exploring honokiol, a phenolic compound from Chinese herbal medicine, we investigated its impact on NLRP3 inflammasome activation in N. gonorrhoeae-infected macrophages.Methods: Honokiol’s impact on the protein expression of pro-inflammatory mediators was analyzed using ELISA and Western blotting. The generation of intracellular H2O2 and mitochondrial reactive oxygen species (ROS) was detected through specific fluorescent probes (CM-H2DCFDA and MitoSOX, respectively) and analyzed by flow cytometry. Mitochondrial membrane integrity was assessed using specific fluorescent probes (MitoTracker and DiOC2(3)) and analyzed by flow cytometry. Additionally, the effect of honokiol on the viability of N. gonorrhoeae was examined through an in vitro colony-forming units assay.Results: Honokiol effectively inhibits caspase-1, caspase-11 and GSDMD activation and reduces the extracellular release of IL-1β, NLRP3, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in N. gonorrhoeae-infected macrophages. Detailed investigations have demonstrated that honokiol lowers the production of H2O2 and the phosphorylation of ERK1/2 in N. gonorrhoeae-infected macrophages. Importantly, the phosphorylation of JNK1/2 and p38 and the activation of NF-κB remain unaffected. Moreover, honokiol reduces the N. gonorrhoeae-mediated generation of reactive oxygen species within the mitochondria, preserving their integrity. Additionally, honokiol suppresses the expression of the pro-inflammatory mediator IL-6 and inducible nitric oxide synthase induced by N. gonorrhoeae independently of NLRP3. Impressively, honokiol exhibits in vitro anti-gonococcal activity against N. gonorrhoeae.Conclusion: Honokiol inhibits the NLRP3 inflammasome in N. gonorrhoeae-infected macrophages and holds great promise for further development as an active ingredient in the prevention and treatment of symptoms associated with gonorrhea.Keywords: Neisseria gonorrhoeae, honokiol, NLRP3 inflammasome, mitochondria, bactericiide

Søren Korsgaard, Frederikke Schønfeldt Troelsen, Katalin Veres, Cecilia Hvitfeldt Fuglsang, Henrik Toft Sørensen Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, DenmarkCorrespondence: Søren Korsgaard, Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Olof Palmes Allé 43– 45, Aarhus N, 8200, Denmark, Tel +45 87167212, Email soren.korsgaard@clin.au.dkPurpose: In the Danish National Patient Registry (DNPR), covering all Danish hospitals and widely used in research, diseases have been recorded using International Classification of Diseases (ICD) codes, transitioning from the Eighth to the Tenth revision in 1994. Uncertainty exists regarding whether including ICD-8 codes alongside ICD-10 is needed for complete disease identification. We assessed the extent of left-truncation and left-censoring in the DNPR arising from omitting ICD-8 codes.Patients and Methods: We sampled 500,000 Danes ≥ 40 years of age in 1995, 2010, and 2018. From the DNPR, we identified cardiovascular, endocrine, gastrointestinal, neurological, pulmonary, rheumatic, and urogenital diseases as well as fractures. We obtained the number of people with a disease recorded with ICD-8 codes only (ie, the ICD-8 record would be left-truncated by not using ICD-8 codes), ICD-8 plus ICD-10 codes (ie, the ICD-8 record would be left-censored by not using ICD-8 codes), and ICD-10 codes only. For each ICD group, we calculated the proportion of people with the disease relative to the total sample (ie, 500,000 people) and the total number of people with the disease across all ICD groups.Results: Overall, the left-truncation issue decreased over the years. Relative to all people with a disease, the left-truncated proportion was for example 59% in 1995 and < 2% in 2018 for diabetes mellitus; 93% in 1995, and 54% in 2018 for appendicitis. The left-truncation issue increased with age group for most diseases. The proportion of disease records left-censored by not using ICD-8 codes was generally low but highest for chronic diseases.Conclusion: The left-truncation issue diminished over sample years, particularly for chronic diseases, yet remained rather high for selected surgical diseases. The left-truncation issue increased with age group for most diseases. Left-censoring was overall a minor issue that primarily concerned chronic diseases.Keywords: epidemiology, methodology, bias, left-truncation, left-censoring

Anna Kurniati,1 Ferry Efendi,2,3 Ismawiningsih Ismawiningsih,1 Nila Mulyani,1 Zakaria Zakaria,1 Retno Ambarwati,1 Hutomo Tuhu Prasetyo,1 Endro Muljandari,1 Irni Damayanti,1 Arif Yustian Maulana Noor,4 Lisa McKenna,3 Iin Nurlinawati5 1Directorate of Health Workforce Deployment, Directorate General of Health Workforce, Ministry of Health, Jakarta, Indonesia; 2Faculty of Nursing, Universitas Airlangga, Surabaya, Indonesia; 3School of Nursing and Midwifery, La Trobe University, Melbourne, Australia; 4Agriculture Socio-Economic Department, Faculty of Agriculture, Brawijaya University, Malang, Indonesia; 5Badan Riset Inovasi Nasional, Jakarta, IndonesiaCorrespondence: Ferry Efendi, Faculty of Nursing, Universitas Airlangga, Campus C Mulyorejo, Surabaya, East Java, 60115, Indonesia, Tel +62 31 591 3754, Email ferry-e@fkp.unair.ac.idIntroduction: Retaining doctors and dentists in remote areas of Indonesia remains a national priority of the Indonesian government. The purpose of this study was to analyze the interventions for retention of doctors and dentists in remote areas using the discrete choice experiment (DCE) approach.Materials and Methods: A DCE was conducted to investigate preferences of doctors and dentists for retention in remote areas. This research was conducted in 78 primary healthcare settings across 15 provinces in Indonesia. The conditional logit model was used to explore stated preferences for each attribute.Results: The total number of respondents was 158, including 113 doctors and 45 dentists. In general, doctors placed the highest preference on getting priority for government scholarships to facilitate retention in remote areas (OR=5.65, p< 0.001). Specifically, dentists preferred security guarantees from local government (OR = 4.87, p< 0.001). Both groups valued having an official residence (OR=3.6, p< 0.001) as a factor for retention in remote areas.Conclusion: Scholarship, security guarantees, housing facilities, and medical facilities were the most considered factors for retaining doctors and dentists in a remote area. This study confirms the importance of a combination of interventions in maintaining doctors and dentists in remote areas. Policy options in the form of non-financial and financial intervention packages can be combined to improve their retention.Keywords: preferences, health systems, health workers, rural area, health workforces, DCE

Bezina Arega Emeru,1 Dejene Getachew Dame,2 Haregawi Tesfaye Desta3 1Animal Biotechnology Research Program, National Agricultural Biotechnology Research Center, Ethiopian Institute of Agricultural Research, Holeta, Ethiopia; 2College of Agriculture and Veterinary Science, Ambo University, Ambo, Ethiopia; 3College of Agricultural and Veterinary Medicine, Jimma University, Jimma, EthiopiaCorrespondence: Bezina Arega Emeru, Animal Biotechnology Research Program, National Agricultural Biotechnology Research Center, Ethiopian Institute of Agricultural Research, P.O. Box 249, Holeta, Ethiopia, Tel +251 960167205, Fax +251112610053, Email bezinaemeru@gmail.comPurpose: The purpose of this research is to detect Newcastle disease virus and to assess the seropositivity among backyard, semi-intensive, and intensive farms located in central and southwestern areas of Ethiopia.Material and Methods: A total of 239 oropharyngeal and cloacal swab samples were collected from symptomatic birds found in Holeta, Burayu, Jimma towns as well as Seka Chekorsa and Nadhigibe woredas of Jimma Zone. In addition, ninety blood samples were collected from wing veins of unvaccinated birds found in the study areas of Jimma zone. Side-by-side information related to risk factors estimated to contribute to the susceptibility of the disease was collected by interviewing owners of sampled birds. Reverse transcription polymerase-chain reaction (RT-PCR) was conducted to detect NDV. Likewise, Enzyme-linked immunosorbent assay (ELISA) was performed to determine the seropositivity of ND.Results: The proportion of samples where NDV was detected was 24.6%. Similarly, 68.9% of the sampled birds were seropositive. It was observed that adult birds were more likely to encounter the disease than youngs (OR = 11.6; 95% CI: 4.0– 33.3; P = 0.000). Birds owned by respondents who leave diseased birds in the flock were more likely infected (OR = 6.2; 95% CI: 1.8– 21.2; P=0.004) as compared to those isolated and mode of disposal of dead chicken significantly affect exposure (OR = 0.13; 95% CI: 0.10– 4.88; P = 0.044). Likewise, access to veterinary services highly likely reduces susceptibility to the disease (OR = 12.4; 95% CI: 3.2– 46.9; P = 0.000). It was also found that birds farmed intensively were the most at risk (OR = 2.8; 95% CI: 0.58– 13.71; P = 0.199).Conclusion: Detection of ND from a significant proportion of sampled birds and their high seropositivity percentage revealed the circulation of the virus in the study areas.Keywords: Newcastle disease, RT-PCR, ELISA, susceptibility

Hamsah S Alqashqri,1 Ahmed Siddiqi,2 Halah T Albar,3 Enas H Alfalogy,1,4 Nahla H Hariri,1 Yosra Z Alhindi,5 Asim M Alshanberi,1 Safaa M Alsanosi,5 Alaa H Falemban5 1Department of Community Medicine and Pilgrims Health Care, Faculty of Medicine, Umm Al Qura University, Makkah, Saudi Arabia; 2Department of Internal Medicine, National Guard Hospital, Jeddah, Saudi Arabia; 3Department of Physiology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 4Family Medicine, Faculty of Medicine, Suez-Canal University, Ismailia, Egypt; 5Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al Qura University, Makkah, Saudi ArabiaCorrespondence: Alaa H Falemban, Email ahfalemban@uqu.edu.saIntroduction: As a result of the physiological decline in renal function that comes with age and the common failure to recognise renal insufficiency, older adults aged 65 and above are at increased risk of receiving medications that are inappropriate for their level of renal function which in turn lead to increased risk of adverse effects. Little is known about how many older adults receive medications that are inappropriate for their level of renal function. This study aimed to determine the prevalence of renally inappropriate medications in elderly adults by reviewing patient files and evaluating the appropriateness of medication doses relative to renal function in patients aged ≥ 65 years at inpatient healthcare departments.Methods: A retrospective cross-sectional study of patients aged ≥ 65 years was conducted, covering cases from 2015 to 2021. Patient’s medical records were reviewed, their renal function and medications lists were evaluated, determined whether they had been prescribed at least one renally inappropriate medication based on drug-dosing recommendations for different degrees of renal function.Results: A total of 317 elderly inpatients were included, 10% of whom had received inappropriate doses relative to their renal function. Glomerular filtration rate was associated with inappropriate dosing in this study. Of the patients CKD stage 5, 36.8% had at least one drug administered at an inappropriate dose, while this figure was 6.5% among the patients at CKD stage 1; this difference was statistically significant (p = 0.001).Conclusion: A notable portion of older adults may be at risk of adverse effects due to inappropriate medication dosing related to their renal function. Further studies with large samples, drug use analyses based on comprehensive geriatric references and a prioritisation of actual outcomes over potential outcomes are needed to further determine elderly adults’ exposure to inappropriate drugs.Keywords: older adults, geriatric, inappropriate medication, healthcare outcomes, elderly inpatients, renally inappropriate medication, physiological decline, healthcare evaluation, insufficiency

Mohab Basem,1 Kasper Bonnesen,1 Lars Pedersen,1 Henrik Toft Sørensen,1 Morten Schmidt1,2 1Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark; 2Department of Cardiology, Gødstrup Regional Hospital, Herning, DenmarkCorrespondence: Mohab Basem, Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Olof Palmes Allé 43– 45, Aarhus N, 8200, Denmark, Tel +45 87167212, Email mohabbasem@gmail.comAim: To examine whether low-density lipoprotein cholesterol (LDL-C) levels influence the cardiovascular risk associated with non-aspirin non-steroidal anti-inflammatory drug (NSAID) use after myocardial infarction (MI).Methods: Using Danish health registries, we conducted a population-based cohort study of all adult patients with first-time MI during 2010– 2020 with an LDL-C value before discharge. Based on the latest LDL-C value, we categorized patients into a low and a high LDL-C group (< 3.0 vs ≥ 3.0 mmol/L). We used time varying Cox regression to compute hazard ratios (HRs) with 95% confidence intervals of the association between NSAID use and a major adverse cardiovascular event (MACE: recurrent MI, ischemic stroke, and all-cause death).Results: We followed 50,573 patients for a median of 3.1 years. While exposed, 521 patients experienced a MACE: 312 in the low LDL-C group and 209 in the high LDL-C group. The HRs for MACE comparing NSAID use with non-use were 1.21 (1.11– 1.32) overall, 1.19 (1.06– 1.33) in the low LDL-C group, and 1.23 (1.07– 1.41) in the high LDL-group. The HRs for recurrent MI and ischemic stroke were comparable between the LDL-C subgroups. The HRs for all-cause death were 1.22 (1.07– 1.39) in the low LDL-C group and 1.54 (1.30– 1.83) in the high LDL-C group. Changing the cut-off value for LDL-C to 1.8 and 1.4 mmol/L showed consistent results.Conclusion: In patients with MI, LDL-C levels did not influence the increased risk of MACE associated with NSAID use, but might influence the association between NSAID use and all-cause death. Keywords: cardiovascular disease, non-steroidal anti-inflammatory drugs, cholesterol, low-density lipoprotein cholesterol, myocardial infarction, effect modification

Aurélie Mailhac,1 Lars Pedersen,1 Anton Pottegård,2 Jens Søndergaard,3 Torben Mogensen,4 Henrik Toft Sørensen,1 Reimar W Thomsen1 1Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark; 2Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark; 3Research Unit of General Practice, Department of Public Health, University of Southern Denmark, Odense, Denmark; 4Danish Pharmacovigilance Council, Danish Medicines Agency, Copenhagen, DenmarkCorrespondence: Reimar W Thomsen, Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark, Email rwt@clin.au.dkPurpose: A surge in the use of semaglutide injection (Ozempic®) approved to treat type 2 diabetes (T2D) has led to a global supply shortage. We investigated contemporary user rates and clinical characteristics of semaglutide (Ozempic®) users in Denmark, and the extent of “off-label” prescribing for weight loss.Patients and Methods: Nationwide population-based cross-sectional study based on linked health registries January 2018 through December 2023. All adults who received a first prescription of semaglutide once weekly (Ozempic®) were included. We examined quarterly rates of new users and total user prevalences, using other glucagon-like peptide-1 receptor agonists and weight loss medications as comparison. We also investigated user characteristics including T2D, glucose control, comedications, and cardiorenal disease.Results: The new user rate of semaglutide (Ozempic®) remained stable at approximately 4 per 1000 adult person-years between 2019 and 2021 and then accelerated, peaking at 10 per 1000 in the first quarter of 2023 after which it declined sharply. User prevalence increased to 91,626 users in Denmark in 2023. The proportion of semaglutide (Ozempic®) new users who had a record of T2D declined from 99% in 2018 to only 67% in 2022, increasing again to 87% in 2023. Among people with T2D who initiated semaglutide (Ozempic®) in 2023, 52% received antidiabetic polytherapy before initiation, 39% monotherapy, and 8% no antidiabetic therapy. Most T2D initiators had suboptimal glucose control, with 83% having an HbA1c ≥ 48 mmol/mol and 68% ≥ 53 mmol/mol despite use of antidiabetic medication, and 29% had established atherosclerotic cardiovascular disease or kidney disease.Conclusion: The use of semaglutide (Ozempic®) in Denmark has increased dramatically. Although not approved for weight loss without T2D, one-third of new users in 2022 did not have T2D. Conversely, most initiators with T2D had a clear medical indication for treatment intensification, and “off-label” use can only explain a minor part of the supply shortage.Keywords: drug utilization, epidemiology, anti-obesity drugs, glucose-lowering drugs, obesity, type 2 diabetes

Sara Hatam,1,&ast; Sean Timothy Scully,2,&ast; Sarah Cook,3,&ast; Hywel T Evans,2,&ast; Alastair Hume,4 Constantinos Kallis,3 Ian Farr,2 Chris Orton,2 Aziz Sheikh,1 Jennifer K Quint3 1Usher Institute, The University of Edinburgh, Edinburgh, UK; 2Population Data Science, Swansea University Medical School, Swansea, UK; 3School of Public Health, Imperial College London, London, UK; 4EPCC, The University of Edinburgh, Edinburgh, UK&ast;These authors contributed equally to this workCorrespondence: Jennifer K Quint, Email j.quint@imperial.ac.ukBackground: Electronic healthcare records (EHRs) are an important resource for health research that can be used to improve patient outcomes in chronic respiratory diseases. However, consistent approaches in the analysis of these datasets are needed for coherent messaging, and when undertaking comparative studies across different populations.Methods and Results: We developed a harmonised curation approach to generate comparable patient cohorts for asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) using datasets from within Clinical Practice Research Datalink (CPRD; for England), Secure Anonymised Information Linkage (SAIL; for Wales) and DataLoch (for Scotland) by defining commonly derived variables consistently between the datasets. By working in parallel on the curation methodology used for CPRD, SAIL and DataLoch for asthma, COPD and ILD, we were able to highlight key differences in coding and recording between the databases and identify solutions to enable valid comparisons.Conclusion: Codelists and metadata generated have been made available to help re-create the asthma, COPD and ILD cohorts in CPRD, SAIL and DataLoch for different time periods, and provide a starting point for the curation of respiratory datasets in other EHR databases, expediting further comparable respiratory research.Keywords: COPD, asthma, ILD, HER, harmonisation, data curation

Zoran Igrutinovi&cacute;,1,2 Hélène Louise Hooimeijer,3 Karim Kentouche,4 Jaco Botha,5 Peter L Turecek,6 Marta Kokot-Kierepa,5 Hanna T Gazda7 1Clinic of Pediatrics, Department of Hemato-Oncology, University Clinical Center of Kragujevac, Kragujevac, Serbia; 2Faculty of Medical Sciences, Department of Pediatrics, University of Kragujevac, Kragujevac, Serbia; 3Pediatric Hematology, Beatrix Children’s Hospital, University Medical Center Groningen, Groningen, the Netherlands; 4Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Jena, Jena, Deutschland; 5Takeda Pharmaceuticals International AG, Zürich, Switzerland; 6Baxalta Innovations GmbH, Part of Takeda, Vienna, Austria; 7Takeda Development Center Americas, Inc., Cambridge, MA, USACorrespondence: Hanna T Gazda, Takeda Development Center Americas, Inc., 650 East Kendall Street, Cambridge, MA, 02142, USA, Tel +1 617 869-2632, Email hanna.gazda@takeda.comIntroduction: Purified factor IX (FIX) concentrate (IMMUNINE®, Takeda Manufacturing Austria AG, Vienna, Austria) is indicated for the treatment and prophylaxis of bleeding episodes in patients with congenital hemophilia B. Data on the use of purified FIX concentrate in patients ≤ 6 years old with congenital hemophilia B are limited.Aim: Document real-world clinical experience with purified FIX concentrate in routine practice for pediatric patients with hemophilia B.Methods: This prospective post-authorization safety surveillance study enrolled patients ≤ 6 years old with moderate or severe hemophilia B (baseline FIX ≤ 5%) who were prescribed purified FIX concentrate, as determined by the treating physician. The planned observation period for each patient was either 12 months or ≥ 50 exposure days, whichever occurred first. The primary endpoints were the occurrence of treatment-related adverse events (AEs) and serious AEs (SAEs), and inhibitor development.Results: Thirteen male patients (mean ± standard deviation age, 3.80 ± 1.76 years) enrolled and received ≥ 1 treatment with purified FIX concentrate. Thirty-two AEs were reported in 6 patients; 4 were SAEs. No AEs were considered related to purified FIX concentrate. No patients developed inhibitory antibodies. Inhibitor testing was not conducted in 2 patients. Eighteen bleeding episodes were treated with purified FIX concentrate in 6 patients. Hemostatic efficacy was rated as either “excellent” or “good” in all patients with an available rating.Conclusion: No treatment-related AEs were reported, and purified FIX concentrate was shown to be effective in treating and preventing bleeding episodes in pediatric patients ≤ 6 years old with hemophilia B.Keywords: factor IX, hemophilia B, pediatrics, post-marketing product surveillance, surgery

Yu-Xian Tang,1,&ast; Zhi-Wei Fan,1,&ast; Jing Li,2,&ast; Hao-Dong Pan,3 Wen-Xin Su,1 Yusanjan Matniyaz,2 Hai-Tao Zhang,4 Yuan-Xi Luo,4 Zhi-Kang Lv,2 Wen-Zhe Wang,2 Ya-Xuan Gao,2 Tuo Pan,2,4 Wan-Zi Xu,1,2 Dong-Jin Wang1– 4 1Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 3Department of Clinical Medicine, Norman Bethune Health Science Center of Jilin University, Changchun, People’s Republic of China; 4Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong-Jin Wang; Wan-Zi Xu, Department of Cardiac surgery, Nanjing Drum Tower Hospital, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Email dongjin_wang@126.com; 582321957@qq.comBackground: Sivelestat, a neutrophil elastase inhibitor, is specifically developed to mitigate the occurrence of acute lung injury (ALI) in individuals who are undergoing cardiovascular surgery. However, its impact on patients who are at a heightened risk of developing ALI after scheduled cardiac surgery has yet to be determined. In order to address this knowledge gap, we undertook a study to assess the efficacy of sivelestat in protecting the lungs of these patients.Methods: We conducted a prospective cohort study involving 718 patients who were at high risk of developing postoperative acute lung injury (ALI) and underwent scheduled cardiac surgery between April 25th, 2022, and September 7th, 2023. Among them, 52 patients received sivelestat (administered at a dosage of 0.2mg/kg/h for 3 days), while 666 patients served as controls, not receiving sivelestat. The control conditions were the same for all patients, including ventilation strategy, extubating time, and fluid management. Subsequently, a propensity-score matched cohort was established, consisting of 40 patients in both the sivelestat and control groups. The primary outcome measure encompassed a composite of adverse outcomes, including 30-day mortality, ALI, acute respiratory distress syndrome (ARDS), and others. Secondary outcomes assessed included pneumonia, ventricular arrhythmias, mechanical ventilation (MV) time, and more.Results: After conducting propensity matching in our study, we observed that there were no significant differences in 30-day mortality between the sivelestat and control groups (0% vs 2.5%, P=0.32). However, the use of sivelestat exhibited a significant reduction in the incidence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) compared to the control group (0% vs 55%, P< 0.01), pneumonia (0 vs 37.5%, P< 0.01), MV time (median:8 hours, IQR:4– 14.8 hours vs median: 15.2 hours, IQR:14– 16.3 hours, P< 0.01). Compared to the control group, the sivelestat could significantly decrease white cell count (P< 0.01), neutrophile percentage (P< 0.01) and C-reactive protein (P< 0.01) in the period of postoperative 5 days.Conclusion: The prophylactic administration of sivelestat has shown promising results in reducing the occurrence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with a heightened risk of developing these conditions after elective cardiac surgery. Our study findings indicate that sivelestat may provide protective effects by suppressing inflammation triggered by neutrophil activation, thereby safeguarding pulmonary function.Registration: ChiCTR2200059102, https://www.chictr.org.cn/showproj.html?proj=166643.Keywords: sivelestat, cardiac surgery, acute lung injury, inflammation

Nguyen Van An,1,&ast; Le Ha long Hai,2,3,&ast; Vu Huy Luong,4,5 Nguyen Thi Ha Vinh,5,6 Pham Quynh Hoa,7 Le Van Hung,5,7 Nguyen Thai Son,1 Le Thu Hong,1 Dinh Viet Hung,8 Hoang Trung Kien,9 Minh Nhat Le,10,11 Nguyen Hoang Viet,12 Duc Hoang Nguyen,13 Ngai Van Pham,14 Ta Ba Thang,15 Tran Viet Tien,16 Le Huy Hoang17 1Department of Microbiology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 2Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 3Department of Biochemistry, Hematology and Immunology, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 4Department of Laser and Skin Care, National hospital of Dermatology and Venereology, Hanoi, Vietnam; 5Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; 6Department of General Planning, National hospital of Dermatology and Venereology, Hanoi, Vietnam; 7Department of Microbiology, Mycology and Parasitology, National hospital of Dermatology and Venereology, Hanoi, Vietnam; 8Department of Psychiatry, Military Medical 103, Vietnam Military Medical University, Hanoi, Vietnam; 9Department of Immunology, Vietnam Military Medical University, Hanoi, Vietnam; 10Tay Nguyen Institute of Science Research, Vietnam Academy of Science and Technology, VAST, Hanoi, Vietnam; 11Antimicrobial Resistance Research Center, National Institute of Infectious Disease, Tokyo, Japan; 12Molecular Pathology Department, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 13Cardiovascular Laboratories, Methodist Hospital, Merrillville, Indiana, USA; 14Medical Testing Center, Medlatec Group, Hanoi, Vietnam; 15Respiratory Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 16Department of Infectious diseases, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 17Department of Bacteriology, National of Hygiene and Epidemiology, Hanoi, Vietnam&ast;These authors contributed equally to this workCorrespondence: Le Huy Hoang, Department of Bacteriology, National of Hygiene and Epidemiology, Hanoi, 100000, Vietnam, Tel + 84 977 803 986, Email lehuyhoang2010@gmail.comPurpose: Staphylococcus aureus is a commensal bacteria species that can cause various illnesses, from mild skin infections to severe diseases, such as bacteremia. The distribution and antimicrobial resistance (AMR) pattern of S. aureus varies by population, time, geographic location, and hospital wards. In this study, we elucidated the epidemiology and AMR patterns of S. aureus isolated from a general hospital in Vietnam.Methods: This was a cross-sectional study. Data on all S. aureus infections from 2014 to 2021 were collected from the Microbiology department of Military Hospital 103, Vietnam. Only the first isolation from each kind of specimen from a particular patient was analyzed using the Cochran–Armitage and chi-square tests.Results: A total of 1130 individuals were diagnosed as S. aureus infection. Among them, 1087 strains were tested for AMR features. Most patients with S. aureus infection were in the age group of 41– 65 years (39.82%). S. aureus isolates were predominant in the surgery wards, and pus specimens were the most common source of isolates (50.62%). S. aureus was most resistant to azithromycin (82.28%), erythromycin (82.82%), and clindamycin (82.32%) and least resistant to teicoplanin (0.0%), tigecycline (0.16%), quinupristin-dalfopristin (0.43%), linezolid (0.62%), and vancomycin (2.92%). Methicillin-resistant S. aureus (MRSA) and multidrug-resistant (MDR) S. aureus were prevalent, accounting for 73.02% and 60.90% of the total strains respectively, and the strains isolated from the intensive care unit (ICU) had the highest percentage of multidrug resistance (77.78%) among the wards.Conclusion: These findings highlight the urgent need for continuous AMR surveillance and updated treatment guidelines, particularly considering high resistance in MRSA, MDR strains, and ICU isolates. Future research focusing on specific resistant populations and potential intervention strategies is crucial to combat this rising threat.Keywords: Staphylococcus aureus, antimicrobial resistance, methicillin-resistant S. aureus, multidrug resistance, Hanoi, Vietnam

Jan P Vandenbroucke,1– 3 Henrik Toft Sørensen,1,4 David H Rehkopf,5 Jaimie L Gradus,6 Johan P Mackenbach,7 M Maria Glymour,8 Sandro Galea,9 Victor W Henderson1,10 1Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark; 2Leiden University, Leiden, Netherlands; 3London School of Hygiene & Tropical Medicine, London, UK; 4Aarhus University Hospital, Aarhus, Denmark; 5Stanford Center for Population Health Sciences, Stanford University, CA, USA; 6Department of Epidemiology, School of Public Health, Boston University, Boston, MA, USA; 7Department of Public Health, Erasmus University Rotterdam, Rotterdam, Holland; 8Department of Epidemiology, Boston University School of Public Health, Boston University, Boston, MA, USA; 9School of Public Health, Boston University, Boston, MA, USA; 10Departments of Epidemiology & Population Health and of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USAAbstract: This paper is a summary of key presentations from a workshop in Iceland on May 3– 4, 2023 arranged by Aarhus University and with participation of the below-mentioned scientists.Below you will find the key messages from the presentations made by:Professor Jan Vandenbroucke, Department of Clinical Epidemiology, Aarhus University, Emeritus Professor, Leiden University; Honorary Professor, London School of Hygiene & Tropical Medicine, UKProfessor, Chair Henrik Toft Sørensen, Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, DenmarkProfessor David H. Rehkopf, Director, the Stanford Center for Population Health Sciences, Stanford University, CA., USProfessor Jaimie Gradus, Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts, USProfessor Johan Mackenbach, Emeritus Professor, Department of Public Health, Erasmus University Rotterdam, HollandProfessor, Chair M Maria Glymour, Department of Epidemiology, Boston University School of Public Health, Boston University, Boston, Massachusetts, USProfessor, Dean Sandro Galea, School of Public Health, Boston University, Boston, Massachusetts, USProfessor Victor W. Henderson, Departments of Epidemiology & Population Health and of Neurology & Neurological Sciences, Stanford University, Stanford, CA, US; Department of Clinical Epidemiology, Aarhus University, Aarhus, DKKeywords: Ageing, Multimorbidity, Social inequality

Hang-Tsung Liu,1,&ast; Cheng-Shyuan Rau,2,&ast; Yueh-Wei Liu,3 Ting-Min Hsieh,1 Chun-Ying Huang,1 Peng-Chen Chien,4 Hui-Ping Lin,4 Chia-Jung Wu,4 Pei-Chin Chuang,5 Ching-Hua Hsieh4 1Department of Trauma Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan; 2Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan; 3Department of General Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan; 4Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan; 5Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan&ast;These authors contributed equally to this workCorrespondence: Pei-Chin Chuang; Ching-Hua Hsieh, Tel +886-7-3454746, Email pcjchuang@gmail.com; m93chinghua@gmail.comIntroduction: RNA modifications mediated by the m6A, m1A, and m5C regulatory genes are crucial for the progression of malignancy. This study aimed to explore the expression of regulator genes for m6A/m5C/m1A methylation at the single-cell level and to validate their expression in cancerous and adjacent para-cancerous liver tissues of adult patients with HCC who underwent tumor resection.Methods: The bulk sequencing from The Cancer Genome Atlas (TCGA) database and the single-cell RNA sequencing (scRNA-seq) data obtained from the Gene Expression Omnibus (GEO) database were used to identify the dysregulated m6A/m5C/m1A genes for hepatocellular carcinoma (HCC). A real-time polymerase chain reaction (real-time PCR) was used to measure the expression of dysregulated m6A/m5C/m1A genes in collected human HCC tissues and compared with adjacent para-cancerous liver tissues. Immune cell infiltration with these significantly expressed methylation-related genes was evaluated using Timer2.0.Results: A discrepancy in m6A/m5C/m1A gene expression was observed between bulk sequencing and scRNA-seq. The clustered heatmap of the scRNA-seq-identified dysregulated m6A/m5C/m1A genes in TCGA cohort revealed heterogeneous expression of these methylation regulators within the cancer, whereas their expression in the adjacent liver tissues was more homogeneous. The real-time PCR validated the significant overexpression of DNMT1, NSUN5, TRMT6, IGF2BP1, and IGFBP3, which were identified using scRNA-seq, and IGFBP2, which was identified using bulk sequencing. These dysregulated methylation genes are mainly correlated with the infiltration of natural killer cells.Discussion: This study suggests that cellular diversity inside tumors contributes to the discrepancy in the expression of methylation regulator genes between traditional bulk sequencing and scRNA-seq. This study identified five regulatory genes that will be the focus of further studies regarding the function of m6A/m5C/m1A in HCC.Keywords: hepatocellular carcinoma, HCC, methylation, N6-methyladenosine, m6A, N1-methyladenosine, m1A, 5-methylcytidine, m5C, bulk sequencing, single-cell RNA sequencing, scRNA-seq

Pei-Chi Lee,1,&ast; Cun-Zhao Li,2,&ast; Chun-Te Lu,3,4,&ast; Min-Han Zhao,2 Syu-Ming Lai,2 Man-Hua Liao,5 Cheng-Liang Peng,6 Hsin-Tung Liu,1 Ping-Shan Lai2 1xTrans Corporate Research and Innovation Center, Taipei City, Taiwan; 2Department of Chemistry, National Chung Hsing University, Taichung, Taiwan; 3Division of Plastic and Reconstructive Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan; 4Institute of Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 5Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan; 6Isotope Application Division, National Atomic Research Institute, Taoyuan, Taiwan&ast;These authors contributed equally to this workCorrespondence: Ping-Shan Lai, Department of Chemistry, National Chung Hsing University, No. 145, Xingda Road, Taichung, 402, Taiwan, Tel +886-4-22840411 ext. 428, Fax +886-4-22862547, Email pslai@email.nchu.edu.twPurpose: Larger nanoparticles of bioactive compounds deposit high concentrations in follicular ducts after skin penetration. In this study, we investigated the effects of microcurrent cloth on the skin penetration and translocation of large nanoparticle applied for wound repair applications.Methods: A self-assembly of curcumin-loaded micelles (CMs) was prepared to improve the water solubility and transdermal efficiency of curcumin. Microcurrent cloth (M) was produced by Zn/Ag electrofabric printing to facilitate iontophoretic transdermal delivery. The transdermal performance of CMs combined with M was evaluated by a transdermal system and confocal microscopy. The CMs/iontophoretic combination effects on nitric oxide (NO) production and inflammatory cytokines were evaluated in Raw 264.7 cells. The wound-healing property of the combined treatment was assessed in a surgically created full-thickness circular wound mouse model.Results: Energy-dispersive X-ray spectroscopy confirmed the presence of Zn/Ag on the microcurrent cloth. The average potential of M was measured to be +214.6 mV in PBS. Large particle CMs (CM-L) prepared using surfactant/cosurfactant present a particle size of 142.9 nm with a polydispersity index of 0.319. The solubility of curcumin in CM-L was 2143.67 μg/mL, indicating 250-fold higher than native curcumin (8.68 μg/mL). The combined treatment (CM-L+M) demonstrated a significant ability to inhibit NO production and increase IL-6 and IL-10 secretion. Surprisingly, microcurrent application significantly improved 20.01-fold transdermal performance of curcumin in CM-L with an obvious escape of CM-L from follicular ducts to surrounding observed by confocal microscopy. The CM-L+M group also exhibited a better wound-closure rate (77.94% on day 4) and the regenerated collagen intensity was approximately 2.66-fold higher than the control group, with a closure rate greater than 90% on day 8 in vivo.Conclusion: Microcurrent cloth play as a promising iontophoretic transdermal drug delivery accelerator that enhances skin penetration and assists CMs to escape from follicular ducts for wound repair applications.Keywords: Zn/Ag electrofabrics, iontophoretic, self-assembly, anti-inflammatory agent, skin penetration, drug delivery

Henrik Toft Sørensen,1 Tina Christensen,1 Hans Erik Bøtker,2 Christian Fynbo Christiansen,1 Cecilia H Fuglsang,1 Sigrid B Gribsholt,1 Frederik Pagh Bredahl Kristensen,1 Kristina Laugesen,1 Anne Sofie D Laursen,1 Mette Nørgaard,1 Morten Schmidt,1 Nils Skajaa,1 Frederikke S Troelsen,1 Lars Pedersen1 1Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkCorrespondence: Henrik Toft Sørensen, Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Olof Palmes Allé 43-45, Aarhus, 8200, Denmark, Tel +45 87 16 82 15, Email hts@clin.au.dkPurpose: Humans are living longer and may develop multiple chronic diseases in later life. The Better Health in Late Life cohort study aims to improve our understanding of the risks and outcomes of multimorbidity in the Danish population.Methods: A randomly-selected sample of Danish residents who were 50– 65 years of age received a questionnaire and an invitation to participate in this study. Respondents completed an online survey between October 2021 and January 2022 which addressed topics that included self-assessed health, mental health, sleep, specific medical conditions, use of painkillers, diet, alcohol consumption, smoking, physical activity, and body composition. This information was linked to the Danish health and social registries (some established in 1943 and onwards) that maintain data on filled prescriptions, hospital records, socioeconomic status, and health care utilization.Results: Responses were received from 115,431 of the 301,244 residents invited to participate (38%). We excluded respondents who answered none of the questions as well as those who provided no information on sex or indicated an age other than 50– 65 years. Of the 114,283 eligible respondents, 54.8% were female, 30.3% were overweight, and 16.7% were obese. Most participants reported a weekly alcohol consumption of less than seven units and 13.3% were current smokers; 5.2% had a history of hospitalization for solid cancer, and 3.0%, 2.3%, 2.0%, and 0.9% reported chronic pulmonary disease, diabetes, stroke, and myocardial infarction, respectively. The most frequently filled prescriptions were for medications used to treat the nervous system and cardiovascular diseases (38.1% and 37.4%, respectively).Keywords: aging, epidemiology, health registries, life course epidemiology, multimorbidity, prospective cohort

Lam Van Nguyen,1 Huy Quang Ly,1 Hau Thi Vo,1 Thao Thanh Pham,2 Nam Ky Nguyen,3 Thi Van Vo,4 Trung Quoc Phan,1 Phuong Thi Ngoc Tran,1 Hung Huynh Vinh Ly,5 Ha Thi Thao Mai1 1Department of Cosmetic Plastic Surgery, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam; 2Department of Dermato-Venereology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam; 3Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam; 4Department of Pediatrics, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam; 5Department of Orthopedics, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, VietnamCorrespondence: Hung Huynh Vinh Ly, Department of Orthopedics, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, No. 179, Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho, 900000, Vietnam, Email 1853010822@student.ctump.edu.vnBackground: Excessive scarring is a common problem that can have significant cosmetic and psychological consequences for patients. Intralesional injection therapy, such as the use of triamcinolone, has emerged as an effective treatment option for hypertrophic scars. The objective of this study was to describe the morphological features of hypertrophic scars, categorize them, and evaluate the efficacy of triamcinolone injection therapy in treating these scars.Materials and Methods: A cross-sectional descriptive study of 80 patients with hypertrophic scars treated with triamcinolone intralesional injection at Can Tho University of Medicine and Pharmacy Hospital from 5/2018 to 5/2021.Results: There were 80 patients in all, with a male/female ratio of 1/1.05 and a median age of 15– 35. There were 129 scars in all, with scar age > 1 year accounting for 83%, keloid scars accounting for 64%, and hypertrophic scars accounting for the remaining 36%. Scars are most commonly seen on the trunk, accounting for 53.5% of all scars, particularly on the anterior chest wall. When the source of scars was discovered, trauma and acne accounted for 24% and 23%, respectively, while the rest were predominantly spontaneous scars, accounting for 49%. Scarring and discomfort of mild to moderate severity were common clinical symptoms; scars larger than 5cm in size had more symptoms than scars smaller than 5cm. Prior to the therapy, the mean Vancouver Score Scale-VSS was 6.55± 2.13. After 24 weeks of the therapy, 96.7% of patients had entirely improved itching symptoms, 75% had completely improved pain, and 25% still had minimal pain. After therapy, the mean Vancouver Score Scale-VSS was 2.55± 1.81 (p< 0.05). At week 24, 3.75% of patients experienced skin shrinkage, 3.75% experienced depigmentation, and 13.75% experienced vasodilation.Conclusion: Triamcinolone intralesional injection should be utilized as a first-line therapy for hypertrophic scarring.Plain Language Summary: This study looked at the effectiveness of triamcinolone injection (TAC) therapy in treating hypertrophic scars, which can cause significant cosmetic and psychological problems for patients. The study included 80 patients who had hypertrophic scars and were treated with triamcinolone injections over a period of 24 weeks. The majority of the scars were keloid scars (64%) and had an age of over one year (83%). Scars were most commonly found on the trunk, especially the anterior chest wall. The most common sources of scarring were trauma and acne. Mild to moderate scarring and discomfort were common symptoms, with larger scars having more symptoms. Before treatment, the mean Vancouver Score Scale-VSS was 6.55± 2.13. After 24 weeks of treatment, 96.7% of patients had improved itching symptoms, 75% had improved pain, and 25% still had minimal pain. The mean Vancouver Score Scale-VSS was also significantly reduced after treatment (2.55± 1.81). Some side effects were observed, such as skin shrinkage, depigmentation, and vasodilation, but these were experienced by a small percentage of patients. Based on these results, the study concludes that triamcinolone injection therapy should be considered as the first-line treatment for hypertrophic scarring. This therapy was found to be effective in reducing symptoms and the overall appearance of scars, with few side effects. This study provides valuable information for healthcare professionals who treat patients with hypertrophic scars, and may help improve the quality of life for those affected by this condition.Keywords: clinical features, hypertrophic scar, triamcinolone intralesional injection

Kuo-Feng Hua,1,2,&ast; Lan-Hui Li,3,&ast; Hsin-Chiao Yu,4 Wei-Ting Wong,1 Hsien-Ta Hsu4,5 1Department of Biotechnology and Animal Science, National Ilan University, Yilan, 26047, Taiwan; 2Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404333, Taiwan; 3Department of Laboratory Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, 108, Taiwan; 4Division of Neurosurgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, 231, Taiwan; 5School of Medicine, Buddhist Tzu Chi University, Hualien, 970, Taiwan&ast;These authors contributed equally to this workCorrespondence: Hsien-Ta Hsu, Division of Neurosurgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289, Jianguo Road, Xindian Dist, New Taipei City, 231016, Taiwan, Tel +866-2-6628-9779, Email j1208192@ms45.hinet.netPurpose: Intervertebral disc (IVD) degeneration, associated with aging, may cause low back pain and disability, with obesity as a significant risk factor. In a prior study, we found a positive correlation between IVD degeneration and levels of matrix metalloproteinase-1 (MMP-1) and leptin. Yet, the interaction between MMP-1 and leptin in IVD degeneration is unclear. Our research seeks to explore leptin’s influence on MMP-1 expression and the underlying mechanisms in human intervertebral disc cartilage endplate-derived stem cells, specifically SV40 cells.Methods: The mRNA and protein expression in leptin-stimulated SV40 cells were assessed using RT-real-time PCR and Western blotting or ELISA, respectively. We examined leptin-mediated RhoA activation through a GTP-bound RhoA pull-down assay. Furthermore, the phosphorylation levels of mitogen-activated protein kinases and AKT in leptin-stimulated SV40 cells were analyzed using Western blotting. The activation of NF-κB by leptin was investigated by assessing phosphorylation of IKKα/β, IκBα, and NF-κB p65, along with the nuclear translocation of NF-κB p65. To understand the underlying mechanism behind leptin-mediated MMP-1 expression, we employed specific inhibitors.Results: Leptin triggered the mRNA and protein expression of MMP-1 in SV40 cells. In-depth mechanistic investigations uncovered that leptin heightened RhoA activity, promoted ERK1/2 phosphorylation, and increased NF-κB activity. However, leptin did not induce phosphorylation of JNK1/2, p38, or AKT. When we inhibited RhoA, ERK1/2, and NF-κB, it resulted in a decrease in MMP-1 expression. Conversely, inhibition of reactive oxygen species and NADPH oxidase did not yield the same outcome. Additionally, inhibiting RhoA or ERK1/2 led to a reduction in leptin-induced NF-κB activation. Moreover, inhibiting RhoA also decreased leptin-mediated ERK1/2 phosphorylation.Conclusion: These results indicated that leptin induced MMP-1 expression in SV40 cells through the RhoA/ERK1/2/NF-κB axis. This study provided the pathogenic role of leptin and suggested the potential therapeutic target for IVD degeneration. Keywords: intervertebral disc degeneration, leptin, matrix metalloproteinase, intervertebral disc cartilage endplate-derived stem cells, RhoA, ERK1/2

Chanda Simfukwe, Su-Hyun Han, Ho Tae Jeong, Young Chul Youn Department of Neurology, Chung-Ang University College of Medicine, Seoul, South KoreaCorrespondence: Young Chul Youn; Su-Hyun Han, Department of Neurology, Chung-Ang University Hospital, Seoul, Republic of Korea, Email neudoc@cau.ac.kr; freesu84@cau.ac.krPurpose: Electroencephalography (EEG) is a non-intrusive technique that provides comprehensive insights into the electrical activities of the brain’s cerebral cortex. The brain signals obtained from EEGs can be used as a neuropsychological biomarker to detect different stages of Alzheimer’s disease (AD) through quantitative EEG (qEEG) analysis. This paper investigates the difference in the abnormalities of resting state EEG (rEEG) signals between eyes-open (EOR) and eyes-closed (ECR) in AD by analyzing 19-scalp electrode EEG signals and making a comparison with healthy controls (HC).Participants and Methods: The rEEG data from 534 subjects (ages 40– 90) consisting of 269 HC and 265 AD subjects in South Korea were used in this study. The qEEG for EOR and ECR states were performed separately for HC and AD subjects to measure the relative power spectrum density (PSD) and coherence with functional connectivity to evaluate abnormalities. The rEEG data were preprocessed and analyzed using EEGlab and Brainstorm toolboxes in MATLAB R2021a software, and statistical analyses were carried out using ANOVA.Results: Based on the Welch method, the relative PSD of the EEG EOR and ECR states difference in the AD group showed a significant increase in the delta frequency band of 19 EEG channels, particularly in the frontal, parietal, and temporal, than the HC groups. The delta power band on the source level was increased for the AD group and decreased for the HC group. In contrast, the source activities of alpha, beta, and gamma frequency bands were significantly reduced in the AD group, with a high decrease in the beta frequency band in all brain areas. Furthermore, the coherence of rEEG among different EEG electrodes was analyzed in the beta frequency band. It showed that pair-wise coherence between different brain areas in the AD group is remarkably increased in the ECR state and decreased after subtracting out the EOR state.Conclusion: The findings suggest that examining PSD and functional connectivity through coherence analysis could serve as a promising and comprehensive approach to differentiate individuals with AD from normal, which may benefit our understanding of the disease.Keywords: Alzheimer’s disease, electroencephalography, power spectral density, coherence

Hai-Tao Zhang,1 Kuo Wang,2 Ze-Shi Li,1 Chuang-Shi Wang,3 Xi-Kun Han,4,5 Wei Chen,6 Fu-Dong Fan,7 Jun Pan,7 Qing Zhou,7 Hai-Long Cao,7 Hao-Dong Pan,8 Xiateke Hafu,9 Chen Li,10 Guo-Liang Fan,10 Tuo Pan,1 Dong-Jin Wang,1,2,6,7 Wei Wang9 1Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, Jiangsu, 210008, People’s Republic of China; 2Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, the Affiliated Clinical College of Xuzhou Medical University, Nanjing, Jiangsu, 210008, People’s Republic of China; 3Medical Research and Biometrics Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 102300, People’s Republic of China; 4Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA; 5Program in Genetic Epidemiology and Statistical Genetics, Harvard T. H. Chan School of Public Health, Boston, MA, USA; 6Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210008, People’s Republic of China; 7Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, People’s Republic of China; 8Department of Clinical Medicine, Norman Bethune Health Science Center of Jilin university, Changchun, Jilin, 130021, People’s Republic of China; 9The Xinhua Hospital of Ili Kazak Autonomous Prefecture, Ili, Xinjiang, People’s Republic of China; 10Department of Cardiac Surgery, Dong Fang Hospital Affiliated to Tongji University, Shanghai, 200120, People’s Republic of ChinaCorrespondence: Dong-Jin Wang, Chief of department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Number 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Email dongjin_wang@126.com Wei Wang, The Xinhua Hospital of Ili Kazak Autonomous Prefecture, Ili, Xinjiang, People’s Republic of China, Email wangwei3342@163.comBackground: Early postoperative bacterial pneumonia and sepsis (ePOPS), which occurs within the first 48 hours after cardiovascular surgery, is a serious life-threatening complication. Diagnosis of ePOPS is extremely challenging, and the existing diagnostic tools are insufficient. The purpose of this study was to construct a novel diagnostic prediction model for ePOPS.Methods: Least Absolute Shrinkage and Selection Operator (LASSO) with logistic regression was used to construct a model to diagnose ePOPS based on patients’ comorbidities, medical history, and laboratory findings. The area under the receiver operating characteristic curve (AUC) was used to evaluate the model discrimination.Results: A total of 1203 patients were recruited and randomly split into a training and validation set in a 7:3 ratio. By early morning on the 3rd postoperative day (POD3), 103 patients had experienced 133 episodes of bacterial pneumonia or sepsis (15 patients had both). LASSO logistic regression model showed that duration of mechanical ventilation (P=0.015), NYHA class ≥ III (P=0.001), diabetes (P< 0.001), exudation on chest radiograph (P=0.011) and IL-6 on POD3 (P< 0.001) were independent risk factors. Based on these factors, we created a nomogram named DICS-I with an AUC of 0.787 in the training set and 0.739 in the validation set.Conclusion: The DICS-I model may be used to predict the risk of ePOPS after cardiovascular surgery, and is also especially suitable for predicting the risk of IRAO. The DICS-I model could help clinicians to adjust antibiotics on the POD3.Keywords: early postoperative pneumonia and sepsis, IL-6, LASSO, nomogram

Fang-bo Li,1,&ast; Ping Lu,2,&ast; Hai-tao Wu,1 Ming-han Wang,1 Jing-dong Wang1 1Graduate School, Guangzhou Sport University, Guangzhou, Guangdong, 510500, People’s Republic of China; 2School of PE and Health, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang-bo Li, Graduate School, Guangzhou Sport University, Linhe West Road, Tianhe District, Guangzhou, Guangdong, 510500, People’s Republic of China, Tel +86 18860292906, Email 975394244@qq.comObjective: To assess the therapeutic impacts of exercise, massage, and music interventions on college students experiencing depression by employing a mesh meta-analysis approach. This research intends to offer valuable insights to aid in the development of non-pharmaceutical treatment strategies for depression.Methods: We conducted a thorough search across various databases including Cochrane, PubMed, Embase, Web of Science, CNKI, and Wanfang to explore the effects of music, massage, aerobic exercise, fitness Qigong, yoga, tai chi, ball games, strength training, dance, whole body vibration training, and high-intensity interval training on the treatment of depression in college students. The search period was from January 1, 2023, which marks the establishment of each database. Subsequently, a mesh meta-analysis was performed using the “Stata 15.1” software, incorporating outcome indicators from 24 included literature comprising a total of 1458 patients.Results: Based on the ranking of the optimal intervention effects of various non-pharmaceutical methods, the order, from highest to lowest probability, was as follows: high-intensity interval training (96%), yoga (94.90%), dance (78.30%), music (73.30%), ball games (62.50%), strength training (51.70%), aerobic training (45.30%), tai chi (35.40%), vibration training (27.30%), massage (20.10%), qigong (14.30%), and no intervention (1.00%). This ranking aligns closely with the findings obtained from pairwise comparisons between different interventions.Conclusion: High-intensity interval training is likely to yield the most effective therapeutic results for college students with depression. In the pairwise comparison of different interventions, High-intensity interval training is also better than most interventions. However, to establish its intervention effect more conclusively, further validation through additional high-quality randomized controlled trials is necessary.Keywords: depression, music, exercise, college student, network meta-analysis

Hatim Almahdi,1 Tariq Abdullatif Alnaeem,2 Hussien Tawfiq Alshawaf,2 Ahmed Jassim Alsubaya,2 Abdullah Amin Bu Hulayqah,2 Mohammed Yaseer Al khars2 1Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, King Faisal University, AlAhsaa, Saudi Arabia; 2King Faisal University Dental Complex, College of Dentistry, King Faisal University, AlAhsaa, Saudi ArabiaCorrespondence: Hatim Almahdi, Email hyagoob@kfu.edu.saIntroduction: Assessing graduates’ performance is essential to identify the strengths and weaknesses in dental education. This study examined the self-perceived preparedness of dental graduates at King Faisal University (KFU), Saudi Arabia, using the Dental Undergraduates Preparedness Assessment Scale (DU-PAS).Materials and Methods: Using a cross-sectional design, this study assesses dental graduates’ preparedness. This assessment measures various skills and attributes expected of dental graduates based on the DU-PAS. From January to April 2021, an electronic form was distributed to 102 eligible dental graduates of KFU. The response rate was 92.15%. The total preparedness score ranged from 0 to 100. The questionnaire consisted of two parts, the first investigating preparedness in clinical procedures (24 items) and the second investigating preparedness regarding cognition, communication, and professionalism skills (26 items). Data are analyzed using SPSS Descriptive analysis using frequencies and percentages.Results: The study included 94 participants, all of them male, with a response rate of 92.4%, who graduated from the College of Dentistry KFU in Saudi Arabia. The participants’ median age was 25. The mean DU-PAS score for the participants was 79.08 (SD ± 12.15; range, 47.84– 100). The mean score for Part A of the scale, which comprises the clinical skills, was 84.55 (SD ± 13.56; range, 43.75– 100). It revealed that participants felt they had no experience with the four procedures. The mean score for Part B of the scale comprising cognitive and behavioural attributes was 73.60 (SD ± 16.29; range, 36.54– 100). More than one-third of the participants reported limited experience in attributes related to items B30 (suspected oral cancer, 36.2%), and B33 (evaluating new dental materials, 22.3%).Conclusion: In this study, dental graduates of KFU reported a high level of self-perceived confidence in their skills. Consequently, they will be able to integrate seamlessly into general dental practice. However, the participants’ feedback reflects certain deficiencies in practising specific clinical procedures.Keywords: DU-PASS, preparedness, dental graduates, Saudi Arabia, self-perceived, assessment

Vagner Loduca Lima,1 Larissa Caroline Mansano Soares,1 Leonardo Amarante Pereira,1 Priscila Alves Nascimento,1 Luciano Rabello Netto Cirillo,1 Hebert Toshiaki Sakuma,1 Glaucia Luciano da Veiga,1,2 Julio Zaki Abucham-Neto,1 Fernando Luiz Affonso Fonseca1– 3 1Departamento de Oftalmologia, Faculdade de Medicina do ABC, Santo André, Brazil; 2Laboratório de Análises Clínicas, Faculdade de Medicina do ABC, Santo André, Brasil; 3Departamento de Ciências Farmacêuticas da Universidade Federal de São Paulo/UNIFESP, Diadema, BrasilCorrespondence: Glaucia Luciano da Veiga, Departamento de Oftalmologia, Faculdade de Medicina ABC, 2000 Lauro Gomes Avenue, Santo André, SP, 09069-870, Brazil, Tel +55 11 4993-5488, Email grlveiga@gmail.comBackground and Aim: To identify ocular findings related to SARS-CoV-2 infection in patients after the resolution of COVID-19 using complete ocular examinations and optical coherence tomography (OCT).Methods: In this cross-sectional study, conducted from May 30 to October 30, 2020, patients who recovered from various stages COVID-19 underwent eye examination and multimodal retinal imaging (Retinographies and Spectral-OCT).Results: We included 50 patients, 29 (58%) males, median age of 46.5 [standard deviation 15.8]. Of these, 42% (21) had mild, 18% (9) had severe and 40% (20) had critical disease. The median time interquartile range (IQR) between symptom onset and ocular examination was 55 days [IQR 39– 71]. Seven patients (14%) reported ophthalmic symptoms, transitory low visual acuity (6%) and retroocular pain (8%). On OCT, one patient without comorbidities had sectoral retinal pallor suggestive of acute retinal ischaemia and oedema of the retina’s inner layers and atrophy. All findings progressively and spontaneously improved months after resolution of COVID-19.Conclusion: Patients with COVID-19 present findings compatible with the general population depending on age and comorbidities; nevertheless, acute retinal findings associated with the disease may be present, such as caused either by the direct effects of retinal SARS-CoV-2 infection, by indirect effects of the cytokine storm or by the pro-thrombotic state associated with COVID-19. Therefore, retinal involvement in patients with COVID-19 remains subject to considerable discussion and study.Keywords: COVID-19, retina, ophthalmology, Sars-Cov-2, eye manifestations

Fang Yuan,1,&ast; Feng-Na Zhu,2,&ast; Xiao-Juan Liu,1,&ast; Jun Li,3 Hong-Tao Xu1 1Department of Pediatrics, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, 430070, People’s Republic of China; 2Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Wuhan, 430070, People’s Republic of China; 3Department of Blood Purification, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, 430070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li; Hong-Tao Xu, General Hospital of Central Theater Command of the People’s Liberation Army, 627&num;, Wuluo Road, Wuchang District, Wuhan, Hubei Province, 430070, People’s Republic of China, Tel +86-13659846692, Fax +86-27-50773333, Email lijun15261@163.com; xuht5409@163.comBackground: Incontinentia pigmenti (IP), also known as Bloch-Sulzberger syndrome, is an X-linked dominant genetic disease involving multiple systems. Previous literature has not reported the case of parents with negative genetic test results, and typical early clinical symptoms and auxiliary inspection results were also lacking.Case Report: A female child was found to have broken skin immediately after birth with no family inheritance disease, and the area of the broken skin increased. Immediately afterward, Head magnetic resonance imaging (MRI) showed multiple blood lesions in the brain. Then, the wide-angle digital retinal imaging system suggesting that fundus fluorescein angiography showed fundus vascular loop-like changes. And blood genetic testing showed that exons 4– 10 of the NEMO gene located in Xq28 were deleted. The patient was eventually diagnosed with IP. However, her parents were a non-consanguineous healthy couple, with no specific skin, oral, or perineal diseases. And her parents’ blood genetic testing showed that the parents and sisters of the patient did not have the NEMO gene exon deletion of Xq28.Conclusion: This case demonstrates the process from suspected neonatal IP cases without familial inheritance to diagnosis, which showed the typical early clinical symptoms and auxiliary inspection results. This case showed that the parents of patients with IP do not necessarily have clinical symptoms and positive symptoms of genetic testing results.Keywords: incontinentia pigment, genodermatosis, Bloch-Sulzberger syndrome, skin disease, NEMO gene

Søren Hauge Okholm,1 Dávid Nagy,1 Dóra Körmendiné Farkas,1 Cecilia Hvitfeldt Fuglsang,1 Frederikke Schønfeldt Troelsen,1 Victor W Henderson,1,2 Henrik Toft Sørensen1 1Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 2Departments of Epidemiology & Population Health and of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USACorrespondence: Henrik Toft Sørensen, Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Olof Palmes Allé 43-45, Aarhus N, 8200, Denmark, Tel +45 87 16 82 15, Email hts@clin.au.dkIntroduction: Cancer may increase the risk of bleeding. However, whether subdural hematoma is a marker of occult cancer remains unknown. We examined the association between non-traumatic subdural hematoma and cancer risk in a cohort study.Materials and Methods: Using Danish nationwide health registries, we identified 2713 patients with non-traumatic subdural hematoma and no previous cancer diagnosis, who were hospitalized between April 1, 1996 and December 31, 2019. We computed age-, sex-, and calendar year-standardized incidence ratios (SIRs) as the ratio of the observed to expected number of patients with cancer by using national incidence rates as reference as a measure of relative risk.Results: We identified 77 cancer cases within the first year of follow-up and 272 cancer cases thereafter. The one-year risk of cancer was 2.8% (95% confidence interval: 2.2– 3.5), and the one-year SIR was 1.7 (95% confidence interval: 1.3– 2.1). During the subsequent years, the SIR was 1.0 (95% confidence interval: 0.9– 1.1). The relative risk was elevated for some hematological and liver cancers.Conclusion: The risk of a new cancer diagnosis was clearly increased in patients with non-traumatic subdural hematoma compared with the general population during the first year of follow-up. However, the absolute risk was low, thus limiting the clinical relevance of pursuing early cancer detection in these patients.Keywords: cancer, cohort study, epidemiology, non-traumatic subdural hematoma, population-based

Hui Pi,1,2,&ast; Ming-Fang Xu,3,&ast; Hai-Tao Lu3 1Yangtze University Health Science Center, Jingzhou, 434020, People’s Republic of China; 2Department of Otolaryngology, GongAn County People’s Hospital, Jingzhou, 434300, People’s Republic of China; 3Department of Otolaryngology, Jingzhou Central Hospital, Jingzhou, 434020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hai-Tao Lu, Department of Otolaryngology, Jingzhou Central Hospital, No. 26 Chuyuan Avenue, Jingzhou District, Jingzhou, 434020, People’s Republic of China, Tel +86 18107167033, Email haitaolu02@126.comObjective: To investigate the expression and correlation of autophagy-related microtubule-associated protein 1 light chain 3 beta LC3 and interleukin-5 IL-5 in allergic rhinitis AR.Methods: Fifty-six 7-week-old BALC/C mice were randomly divided into experimental group (n = 56) and control group (n = 8). The experimental group used Dermatophagoides farinae (Der f) for AR modeling, and control group used PBS solution. As the experimental group sampled at 6 time points, and 8 mice were sacrificed each time, while the control group was sacrificed 24 hours after the last dose. The contents of serum IL-4, IL-5, and dust mite specific IgE HDM-sIgE in mice were detected by enzyme-linked immunosorbent assay ELISA, and the morphological changes of nasal mucosa were detected by a hematoxylin-eosin H&E staining. The expression of LC3 in mouse nasal mucosa was detected by immunohistochemical staining. Spearman correlation coefficient was used to assess the relationship between LC3 and IL-5 levels.Results: In AR mice modelled with dust mites, the serum levels of IL-4 and HDM-sIgE increased gradually, and the serum IL-5 concentration had a peak at the early intraperitoneal administration stage similar to that at the end of modelling. The LC3 level in nasal mucosa of AR mice modelled with dust mites increased gradually in the early stages, but stabilized in the later stages. The expression of LC3 level in nasal mucosa was a positively correlated ration between serum IL-5 level in AR mice.Conclusion: In the early stage of AR mice, the level of nasal mucosal autophagy and serum IL-5 levels were significantly increased and correlated, suggesting that nasal mucosal autophagy played a promoting role in the early stage of AR.Keywords: allergic rhinitis, animal model, autophagy IL-5

Nam Quang Tran,1,2 Bao Hoang Le,1 Chi Khanh Hoang,1 Huu-Thinh Nguyen,3 Truc Thanh Thai4 1Department of Endocrinology, University Medical Center at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Department of Endocrinology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 3Department of Health Checkup, University Medical Center at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 4Faculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, VietnamCorrespondence: Truc Thanh Thai, University of Medicine and Pharmacy at Ho Chi Minh City, 217 Hong Bang, Ward 11, District 5, Ho Chi Minh City, Vietnam, Tel +84 908 381 266, Email thaithanhtruc@ump.edu.vnBackground: Thyroid nodule is a common disorder normally detected by ultrasound. However, little is known about the population prevalence of thyroid nodules in a Vietnamese population. This study aimed to estimate the prevalence of thyroid nodules, its characteristics, and associated factors in a large number of people undergoing annual health checkups.Methods: A retrospective, cross-sectional descriptive study was conducted, based on electronic medical records of people undergoing health checkups at the Health Checkup Department, University Medical Center at Ho Chi Minh City. All of the participants underwent thyroid ultrasonography, anthropometric measurements, and serum examinations.Results: A total of 16,784 participants (mean age: 40.4 ± 12.7 years, 45.1% female) were included in this study. The overall prevalence of thyroid nodules was 48.4%. The mean diameter of nodules was 7.2 ± 5.8 mm. The prevalence of nodules with malignant characteristics was 36.9%. Women had a significantly higher prevalence of thyroid nodules than men (55.2% vs 42.9%, p< 0.001). Advanced age, hypertension, and hyperglycemia were significantly associated with thyroid nodules in both genders. In men, significant factors also included increased body mass index. In women, these included increased total cholesterol and LDLc, hypertriglyceridemia, and hyperuricemia.Conclusion: This study showed a high prevalence of TNs in Vietnamese people undergoing general health checkups. Importantly, the proportion of TNs with malignant risk was quite high. Therefore, screening for TNs should be added to annual health checkups to improve early detection of TNs, targeting those who have a high-risk profile based on factors identified in this study.Keywords: thyroid nodules, malignant thyroid nodules, thyroid ultrasound, general health checkup

Karin EM Diderich, Jasmijn E Klapwijk, Vyne van der Schoot, Hennie T Brüggenwirth, Marieke Joosten, Malgorzata I Srebniak Department of Clinical Genetics, Erasmus MC, Rotterdam, the NetherlandsCorrespondence: Karin EM Diderich, Department of Clinical Genetics, Erasmus MC, Wytemaweg 50, Rotterdam, the Netherlands, Tel +31 10 70 43214, Email k.diderich@erasmusmc.nlAbstract: The yield of genetic prenatal diagnosis has been notably improved by introducing whole genome chromosomal microarray (CMA) and prenatal exome sequencing (pES). However, together with increased numbers of diagnoses made, the need to manage challenging findings such as variants of unknown significance (VUS) and incidental findings (IF) also increased. We have summarized the current guidelines and recommendations and we have shown current solutions used in our tertiary center in the Netherlands. We discuss four of the most common clinical situations: fetus with normal pES results, fetus with a pathogenic finding explaining the fetal phenotype, fetus with a variant of uncertain clinical significance fitting the phenotype and fetus with a variant leading to an incidental diagnosis. Additionally, we reflect on solutions in order to facilitate genetic counseling in an NGS-era.Keywords: exome sequencing, genetic counseling, prenatal diagnosis, incidental findings, variants of unknown significance, VUS, IF

Ha Thi Thu Tran,1,&ast; Yen Hoang Nguyen,1,&ast; Thuy Dinh Vuong,2 Loi Van Bui,3 Hue Thi Doan,1 Ha Thi Thu Le,1 Thien Cong Le,1 Thai Quoc Nguyen,4 Son Ngoc Do,5 Phuong Doan Nguyen,6 Chinh Quoc Luong,5 Tung Son Vu,7 Son Nam Tran,8 Ngoc Bao Doan,9 Long Bao Hoang,10 Tuan Van Nguyen1,11 1Department of Psychiatry, Hanoi Medical University, Hanoi, Vietnam; 2Department of Schizophrenia, Vietnam National Institute of Mental Health, Hanoi, Vietnam; 3Department of Stress-Related Disorders, Vietnam National Institute of Mental Health, Hanoi, Vietnam; 4Center of Tropical Diseases, Bach Mai Hospital, Hanoi, Vietnam; 5Center for Emergency Medicine, Bach Mai Hospital, Hanoi, Vietnam; 6Outpatient Department, Construction Hospital, Hanoi, Vietnam; 7Department of Mood Disorders, Vietnam National Institute of Mental Health, Hanoi, Vietnam; 8Department of Oncology, Vietnam National Hospital of Traditional Medicine, Hanoi, Vietnam; 9School of Preventive medicine and Public health, Hanoi Medical University, Hanoi, Vietnam; 10Research and Training Management Department, Institute of Gastroenterology and Hepatology, Hanoi, Vietnam; 11Vietnam National Institute of Mental Health, Hanoi, Vietnam&ast;These authors contributed equally to this workCorrespondence: Ha Thi Thu Tran, Email tran_thuha@hmu.edu.vnObjective: To evaluate the prevalence of post-traumatic stress disorder (PTSD) and other psychological disturbances in the Vietnamese healthcare workers (HCWs) at COVID-19 field hospitals.Methods: A cross-sectional study was conducted using the Impact of Event Scale–Revised (IES-R) to measure PTSD and the Depression Anxiety Stress scale (DASS) to measure other psychological disturbances. The anxiety about COVID-19 was evaluated by the fear of COVID-19 (FOC) scale. A self-developed questionnaire was used to assess work conditions and HCW’s major concerns and preparedness. Ordinal logistic regression was used to identify factors associated with the severity of PTSD. A structural modeling equation (SEM) model was fitted to examine the correlation between PTSD and other psychological disturbances.Results: A total of 542 HCWs participated in this study. The prevalence of PTSD was 21.2%, most cases were mild. In the ordinal logistic regression analysis, a history of mental illness, poor preparedness, working in a condition with poor resources, a greater number of concerns, and greater fear of COVID-19 were independently associated with higher severity of PTSD. The prevalence of depression, anxiety, and stress was 46.8%, 38.3%, and 60.2, respectively. In the SEM model, PTSD and psychological disturbances had a strong correlation (standardized covariance 0.86).Conclusion: The prevalence of PTSD and other psychological disturbances was alarmingly high among HCWs who worked at COVID-19 field hospitals. The reported associated factors can be useful for policymakers and health authorities in the preparation for future pandemics.Keywords: PTSD, COVID-19, healthcare workers, DASS, fear of COVID, psychological disturbances

Hou-Hsun Liao,1– 3 Hsiao-Tien Chen,4 Hanoch Livneh,5 Hua-Lung Huang,6 Ning-Sheng Lai,7,8 Ming-Chi Lu,7,8 Chia-Chou Yeh,1,2,9 Tzung-Yi Tsai3,10,11 1Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 2Department of Chinese Medicine, Dalin Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Chiayi, Taiwan; 3Department of Nursing, Tzu Chi University of Science and Technology, Hualien, Taiwan; 4Department of Chinese Medicine, Chi Mei Medical Center, Tainan, Taiwan; 5Rehabilitation Counseling Program, Portland State University, Portland, OR, USA; 6Department of Rehabilitation, Dalin Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Chiayi, Taiwan; 7School of Medicine, Tzu Chi University, Hualien, Taiwan; 8Division of Allergy, Immunology and Rheumatology, Dalin Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Chiayi, Taiwan; 9School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan; 10Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 11Department of Medical Research, Dalin Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Chiayi, TaiwanCorrespondence: Chia-Chou Yeh; Tzung-Yi Tsai, Tel +886-5-2648000-8713 ; +886-5-2648000 ext. 3209, Fax +886-5-2648006, Email yehcc0530@gmail.com; dm732024@tzuchi.com.twObjective: Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used as the first-line agents for the symptomatic relief of rheumatoid arthritis (RA), but it may insidiously provoke the onset of renal diseases, especially chronic kidney disease (CKD). While Chinese herbal medicine (CHM) has become an increasingly popular adjunctive therapy among RA groups, there are currently no available data on the effect of CHM use towards risk of CKD. This study aimed to explore on a population-level whether CHM use decreases sequent CKD risk among them.Methods: In this nested case–control study retrieved from the nationwide insurance database of Taiwan from 2000 to 2012, we looked at the association between CHM use and the likelihood of developing CKD, with a focus on usage intensity. Cases with CKD claims were defined and matched to one randomly selected control case. Conditional logistic regression was then applied to estimate odds ratio (OR) of CKD from CHM treatment measured before the index date. For each OR, we calculated a 95% confidence interval for CHM use relative to the matched control.Results: This nested case–control study included 5464 patients with RA, where after matching comprised 2712 cases and 2712 controls. Among them, there were 706 and 1199 cases that ever received CHM treatment, respectively. After the adjustment, CHM use in RA individuals was related to a lower likelihood of CKD, with an adjusted OR of 0.49 (95% CI: 0.44– 0.56). Additionally, a dose-dependent, reverse association was found between the cumulative duration of CHM use and risk of CKD.Conclusion: Integrating CHM into conventional therapy may reduce the likelihood of developing CKD, which could be a reference in instituting novel preventive strategies to improve treatment outcomes and reduce related fatalities for RA subjects.Keywords: rheumatoid arthritis, chronic kidney disease, Chinese herbal medicine, nested case–control study

Kien Xuan Nguyen,1,&ast; Tien Bui Minh,2,&ast; Hoa Trung Dinh,3,4 Tien Viet Tran,5 Tuan Dinh Le,5,&ast; Nga Phi Thi Nguyen,6 Thi Thanh Hoa Tran,3 Trinh Hien Vu,3 Lan Ho Thi Nguyen,3 Kien Trung Nguyen,2 Nguyen Huy Thong,6 Khanh Do,6 Trung Kien Nguyen,7 Hung Nguyen Dao,8 Son Tien Nguyen6,&ast; 1Department of Military Medical Command and Organization, Vietnam Medical Military University, Ha Noi, Vietnam; 2Department of Obstetrics and Gynecology, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam; 3Department of Requested Treatment, National Hospital of Endocrinology, Ha Noi, Vietnam; 4National Hospital of Endocrinology, Ha Noi, Vietnam; 5Department of Infectious Diseases, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 6Department of Rheumatology and Endocrinology, Military Hospital 103, Vietnam Military Medical University, Ha Noi, Vietnam; 7Hematology and Blood Transfusion Center, Military Hospital 103, Vietnam Military Medical University, Ha Noi, Vietnam; 8Department of Obstetrics and Gynecology, Military Hospital 103, Vietnam Military Medical University, Ha Noi, Vietnam&ast;These authors contributed equally to this workCorrespondence: Son Tien Nguyen, Department of Rheumatology and Endocrinology, Military Hospital 103, Vietnam Military Medical University, 160 Phung Hung Street, Phuc La Ward, Ha Dong District, Hanoi City, Vietnam, Email ntson4879@gmail.comIntroduction: Chronic low-grade inflammation (LGI) plays a role in the pathogenesis of gestational diabetes mellitus (GDM). LGI, on the one hand, promotes insulin resistance and at the same time, affects fetal development. The study aimed to use clinically feasible means to evaluate the association between maternal LGI and maternal insulin resistance and fetal growth indices by ultrasound in the third trimester.Methods: A crossectional and descriptive study on 248 first-time diagnosed GDM in Vietnam.Results: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) indices were significantly higher in GDM than in normal glucose-tolerant pregnancies (p = 0.048 and 0.016, respectively). GDM with LGI witnessed significantly higher systolic blood pressure, BMI, HbA1c, and significantly lower quantitative Insulin Sensitivity Check Index (QUICKI) than those without LGI. After adjusting for maternal BMI, fasting plasma glucose (FPG), age, and parity, C-reactive protein (CRP) was positively correlated with HOMA2-IR (B=0.13, p< 0.01) and Mathews index (B=0.29, p< 0.01). Regarding fetal characteristics, LGI was associated with fetal growth indices in the third trimester of GDM. NLR was negatively correlated with estimated fetal weight (EFW) (B=− 64.4, p< 0.05) after adjusting for maternal BMI and FPG. After adjusting for maternal BMI, FPG, age, and parity, PLR was negatively correlated with biparietal diameter (B=− 0.02, p< 0.01) and abdominal circumference (AC) (B=− 0.16, p< 0.05), and EFW (B=− 1.1, p< 0.01), and head circumference (HC) (B=− 0.06, p< 0.01); CRP was negatively correlated with AC (B=− 0.16, p< 0.001), EFW (B=− 85.3, p< 0.001), and HC (B=− 5.0, p< 0.001).Conclusion: In the third trimester, LGI was associated with maternal glucose and insulin resistance in GDM. Moreover, LGI was associated with fetal characteristics in ultrasonic images. There were negative correlations between LGI and fetal developmental characteristics.Keywords: gestational diabetes mellitus, low-grade inflammation, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, fetal ultrasound parameters

Chantelli Iamblaudiot Razafindrazoto,1 Nitah Harivony Randriamifidy,1 Behoavy Mahafaly Ralaizanaka,2 Jean Tsitamita Andrianoelison,1 Haga Tsilavo Ravelomanantsoa,1 Mialitiana Rakotomaharo,1 Domoina Harivonjy Hasina Laingonirina,1 Sonny Maherison,1 Jolivet Auguste Rakotomalala,3 Anjaramalala Sitraka Rasolonjatovo,1 Andry Lalaina Rinà Rakotozafindrabe,1 Tovo Harimanana Rabenjanahary,1 Soloniaina Hélio Razafimahefa,2 Rado Manitrala Ramanampamonjy1 1Gastroenterology Unit, University Hospital Joseph Raseta Befelatanana, Antananarivo, Madagascar; 2Hepato-Gastroenterology Unit, University Hospital Andrainjato, Fianarantsoa, Madagascar; 3Hepato-Gastroenterology Unit, University Hospital Mahavoky Atsimo, Mahajanga, MadagascarCorrespondence: Chantelli Iamblaudiot Razafindrazoto, Gastroenterology Unit, University Hospital Joseph Raseta Befelatanana, Antananarivo, Madagascar, Email iamblaudiotchantelli@yahoo.comBackground: Cirrhosis is a pathology responsible for a significant hospital morbidity and mortality. The objective of this study was to determine the factors associated with hospital mortality in a sample of Malagasy cirrhotics.Patients and Methods: This was a retrospective cohort study from January 2018 to August 2020 conducted in the Hepato-Gastroenterology Unity, University Hospital Joseph Raseta Befelatanana, Antananarivo, Madagascar.Results: One hundred and eight patients were included. The mean age was 51.13± 13.50 years with a sex ratio of 2.37. The etiology of cirrhosis was dominated by alcohol (44.44%), hepatitis B virus (24.07%) and hepatitis C virus (13.89%). Twenty-eight patients (25.93%) had died. Factors associated with in-hospital mortality were hepatic encephalopathy (OR: 14.16; 95% CI: 5.08– 39.4; p: 0.000), renal failure (OR: 8.55; 95% CI: 2.03– 39.9; p: 0.0034), gastrointestinal bleeding (OR: 3.25; 95% CI: 1.32– 7.92; p: 0.0099), hyponatraemia < 130mmol/L (OR: 3.34; 95% CI: 1.04– 10.6; p=0.046), Child-Pugh C classification (OR: 0.19; 95% CI: 0.12– 0.21; p: 0.000), and MELD-Na score > 32 (OR: 27.5; 95% CI: 4.32– 174.8; p: 0.004).Conclusion: The in-hospital mortality rate during acute decompensation of cirrhosis remains high in Madagascar. Hepatic encephalopathy, renal failure, GI bleeding and hyponatraemia are the main clinico-biological factors affecting in-hospital mortality. Early intervention on these modifiable factors is an important step to improve hospital outcomes. The natraemia, MELD score and MELD-Na score should be used in routine practice in Madagascar to identify patients with acute decompensation of cirrhosis at high risk of death.Keywords: risk factors, in-hospital mortality, liver cirrhosis, Madagascar