Search

BackgroundPoor treatment outcomes among people with drug-resistant TB (DR-TB) are a major concern. Heteroresistance (presence of susceptible and resistant Mycobacterium tuberculosis in the same sample) has been identified in some people with TB, but its impact on treatment outcomes is unknown.MethodsWe used targeted deep sequencing to identify mutations associated with DR-TB and heteroresistance in culture samples of 624 people with DR-TB. We evaluated the association between heteroresistance and time to unfavorable treatment outcome using Cox proportional hazards regression.ResultsThe proportion of drug-resistant isolates with a known mutation conferring resistance was lower for streptomycin (45.2%) and second-line injectables (79.1%) than for fluoroquinolones (86.7%), isoniazid (93.2%) and rifampin (96.5%). Fifty-two (8.3%) had heteroresistance, and it was more common for fluoroquinolones (4.6%) than rifampin (2.2%), second-line injectables (1.4%), streptomycin (1.7%), or isoniazid (1.3%). There was no association between heteroresistance and time to unfavorable outcome among people with multidrug-resistant TB (adjusted hazard ratio [aHR] 1.74, 95% CI 0.39-7.72) or pre-extensively DR-TB (aHR 0.65, 95% CI 0.24-1.72).ConclusionsHeteroresistance was relatively common (8.3%) among people with DR-TB in the Philippines. However, we found insufficient evidence to demonstrate an impact on unfavorable treatment outcomes.

Apart from northern and central China, the fossil record of the latest Miocene and Early Pliocene of Asia is not well documented and the record of South China during this interval is especially poor. Shuitangba, a site in Yunnan Province, offers a rare window into the paleoenvironment of the latest Miocene in southwestern China. Over 2400 vertebrate and macrobotanical specimens have been recovered from the site. The faunal assemblage is dominated by aquatic avian taxa and many of the mammalian taxa are those that indicate densely vegetated, water-margin habitats. Pollen and carpological remains indicate a temperate to subtropical, broad-leaved/coniferous forest around standing water, with more open areas containing grasses and herbs. Analyses of clay minerals, chemical weathering, and enamel stable isotopes suggest that Shuitangba was warmer and more humid than today, possibly with more pronounced seasonality. Results of community structure analysis indicate that the Shuitangba mammalian community was different from those of other Late Miocene Chinese sites in the high proportions of aquatic-dependent mammalian taxa. While Shuitangba shared mammalian faunal elements with other Late Miocene sites in Yunnan, it was still faunally distinct. Further, Shuitangba was depauperate in its mammalian fauna, which may have been a result of the depositional setting rather than a true reflection of regional faunal diversity.

Patients with chronic inflammatory disorders such as psoriasis have an increased risk of cardiovascular disease and elevated levels of LL37, a cathelicidin host defense peptide that has both antimicrobial and proinflammatory properties. To explore whether LL37 could contribute to the risk of heart disease, we examined its effects on lipoprotein metabolism and show that LL37 enhanced LDL uptake in macrophages through the LDL receptor (LDLR), scavenger receptor class B member 1 (SR-B1), and CD36. This interaction led to increased cytosolic cholesterol in macrophages and changes in expression of lipid metabolism genes consistent with increased cholesterol uptake. Structure-function analysis and synchrotron small-angle x-ray scattering showed structural determinants of the LL37-LDL complex that underlie its ability to bind its receptors and promote uptake. This function of LDL uptake is unique to cathelicidins from humans and some primates and was not observed with cathelicidins from mice or rabbits. Notably, Apoe-/- mice expressing LL37 developed larger atheroma plaques than did control mice, and a positive correlation between plasma LL37 and oxidized phospholipid on apolipoprotein B (OxPL-apoB) levels was observed in individuals with cardiovascular disease. These findings provide evidence that LDL uptake can be increased via interaction with LL37 and may explain the increased risk of cardiovascular disease associated with chronic inflammatory disorders.

CUPID is a next-generation neutrinoless double-β decay experiment that will require cryogenic light detectors to improve background suppression, via the simultaneous readout of heat and light channels from its scintillating crystals. In this work, we showcase light detectors based on an alternative Ir-Pt bilayer transition-edge sensor. We have performed a systematic study to improve the thermal coupling between the photon absorber and the sensor, and thereby its responsivity. Our first devices meet CUPID's baseline noise requirement of

Chao-Bang Ma,1,* Cheng-Yang Zhang,1,* Cai-Li Gou,1 Zeng-Hui Liang,1 Jing-Xian Zhang,2 Fei Xing,1,3 Jing-Jing Yuan,1,3 Xin Wei,1,3 Ya-Bing Zhang,1 Zhong-Yu Wang1,3 1Department of Anesthesiology, Pain and Perioperative Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 3Henan Province International Joint Laboratory of Pain, Cognition and Emotion, Zhengzhou, Henan Province, People’s Republic of China; 2The Surgical Department of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhong-Yu Wang, Department of Anesthesiology, Pain and Perioperative Medicine, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou City, Henan Province, People’s Republic of China, Tel +86-13937165514, Email wzy781217@163.comPurpose: Postoperative delirium (POD) is a prevalent and severe complication in elderly patients undergoing major surgery, associated with increased morbidity and mortality. This randomized controlled trial aimed to investigate the effects of low-dose esketamine on the incidence of POD in elderly patients underwent total hip or knee arthroplasty.Patients and Methods: Two hundred and sixty elderly participants were randomly assigned to either the esketamine group (Group E) (0.20mg/kg loading, 0.125mg/kg/h infusion, 0.5 mg/kg for postoperative analgesia) or the placebo group (Group P) (received normal saline). The primary outcome was the incidence of POD, with secondary outcomes including delirium subtypes, duration, intraoperative analgesic consumption, operative and anesthesia times, hemodynamic changes, postoperative pain scores, sleep quality, and common postoperative adverse events.Results: There was no significant difference in the incidence of POD between Group E (8.5%) and Group P (10.8%). No significant differences were observed for the time of delirium onset, duration of delirium, and delirium subtype between the two groups. Patients in the esketamine group had more stable hemodynamic profile after induction and reduced the pain score of motion on the first two days postoperatively but increased the incidence of postoperative dizziness.Conclusion: The repeated infusion of low-dose esketamine did not reduce the incidence of POD during the initial three postoperative days in elderly patients following total hip or knee arthroplasty.Keywords: esketamine, delirium, aged, arthroplasty

Katherine McDermott,1,2 Alexander Mattia Presciutti,1,2 Nadine Levey,1 Julie Brewer,1 Christina L Rush,1,2 Natalia Giraldo-Santiago,1,3 Tony V Pham,1,2 Roger Pasinski,4 Neda Yousif,4 Milton Gholston,4 Vidya Raju,4 Jonathan Greenberg,1,3 Christine S Ritchie,2,3 Ana-Maria Vranceanu1,2 1Center for Health Outcomes and Interdisciplinary Research, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; 2Harvard Medical School, Boston, MA, USA; 3Center for Aging and Serious Illness, Massachusetts General Hospital, Boston, MA, USA; 4MGH Revere HealthCare Center, Revere, MA, USACorrespondence: Ana-Maria Vranceanu, Center for Health Outcomes and Interdisciplinary Research, Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, One Bowdoin Square, 1st Floor, Suite 100, Boston, MA, 02114, USA, Email avranceanu@mgh.harvard.eduPurpose: Chronic pain is highly prevalent and disabling for older adults, particularly those from underserved communities. However, there is an absence of research on how contextual (eg, community/societal) factors interact with pain for these patients. Informed by the socio-ecological model, this study aimed to elucidate the individual, interpersonal, community, and societal factors associated with chronic pain from the perceptions of older adult patients and medical staff in a community clinic.Patients and Methods: In this qualitative study, we conducted four focus groups and two interviews with medical staff (n=25) and three focus groups and seven individual interviews with older adult patients with chronic pain (n=18). Participants were recruited using purposive sampling from an ethnically and economically diverse primary care clinic in the greater Boston community. We transcribed assessments and thematically analyzed data using a hybrid deductive-inductive approach.Results: At the individual level, we identified three themes: (1) older adults with complex care needs, (2) impact of pain (including on physical, emotional, work, and identity functioning), and (3) coping with pain. At the interpersonal level, complex relationships with (1) social supports and (2) medical staff emerged as themes. The need for (1) resources and (2) culturally informed care was identified at the community level, and socioeconomic status impacting the availability of resources for managing chronic pain emerged for the societal domain.Conclusion: Findings underscore the intersection of factors contributing to the experience of pain among older adults from underserved communities. Our findings highlight the need to develop and implement treatments that fully address the experience of older adults with chronic pain at the individual, interpersonal, community, and societal levels.Keywords: community clinic, pain, health disparities

Ting Dai, Qian-Biao Gu, Ying-Jie Peng, Chuan-Lin Yu, Peng Liu, Ya-Qiong He Department of Radiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital), Changsha, Hunan, People’s Republic of ChinaCorrespondence: Ya-Qiong He, Email yaqionghe2021@163.comPurpose: This study aims to explore the value of radiomics combined with clinical parameters in predicting recurrence-free survival (RFS) after the resection of hepatocellular carcinoma (HCC).Patients and Methods: In this retrospective study, a total of 322 patients with HCC who underwent contrast-enhanced computed tomography (CT) and radical surgical resection were enrolled and randomly divided into a training group (n = 223) and a validation group (n = 97). In the training group, Univariate and multivariate Cox regression analyses were employed to obtain clinical variables related to RFS for constructing the clinical model. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were employed to construct the radiomics model, and the clinical-radiomics model was further constructed. Model prediction performance was subsequently assessed by the area under the time-dependent receiver operating characteristic curve (AUC) and calibration curve. Additionally, Kaplan-Meier analysis was used to evaluate the model’s value in predicting RFS. Correlations between radiomics features and pathological parameters were analyzed.Results: The clinical-radiomics model predicted RFS at 1, 2, and 3 years more accurately than the clinical or radiomics model alone (training group, AUC = 0.834, 0.765 and 0.831, respectively; validation group, AUC = 0.715, 0.710 and 0.793, respectively). The predicted high-risk subgroup based on the clinical-radiomics nomogram had shorter RFS than predicted low-risk subgroup in data sets, enabling risk stratification of various clinical subgroups. Correlation analysis revealed that the rad-score was positively related to microvascular invasion (MVI) and Edmondson-Steiner grade.Conclusion: The clinical-radiomics model effectively predicts RFS in HCC patients and identifies high-risk individuals for recurrence.Keywords: Hepatocellular carcinoma, computed tomography, radiomics, recurrence-free survival

Chi-Chen Huang,1 Sheng-Feng Tsai,2,3 Shu-Cheng Liu,4 Mei-Chen Yeh,5 Hao-Chang Hung,5 Chu-Wan Lee,6 Ching-Li Cheng,6 Pei-Ling Hsu,7– 9 Yu-Min Kuo2,3 1Division of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70403, Taiwan; 2Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan; 3Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan; 4Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70403, Taiwan; 5Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi Mei Medical Center, Tainan, 71004, Taiwan; 6Department of Nursing, National Tainan Junior College of Nursing, Tainan, 700007, Taiwan; 7Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; 8Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan; 9Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, 80708, TaiwanCorrespondence: Pei-Ling Hsu, Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan, 80708, Tel +886-7-3121101 ext. 2144#16, Fax +886-7-3119849, Email plhsu@kmu.edu.tw Yu-Min Kuo, Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, 1 Ta Hsueh Road, Tainan, 70101, Taiwan, Tel +886-6-2353535 ext. 5294, Fax +886-6-2093007, Email kuoym@mail.ncku.edu.twIntroduction: Insulin, the key hormone for glucose regulation, has garnered attention for its role as an immune modulator. Impaired insulin signaling in the central nervous system is linked to neuroinflammation and neurodegenerative diseases. Microglia, the resident macrophage-like immune cells in the brain, are key regulators of neuroinflammation. However, the mechanisms by which insulin influences microglial immune responses remain relatively unknown.Methods: This study aimed to assess the effects of post-treatment with insulin [30 minutes after lipopolysaccharide (LPS) exposure] on LPS-induced inflammatory responses in BV2 microglial cells.Results: Post-treatment with insulin potentiated LPS-induced production of nitric oxide and pro-inflammatory cytokines, such as TNF and IL-6, through activation of the Akt/NF-κB pathway. Insulin also enhanced the ability of BV2 cells to phagocytose bacteria particles and β-amyloid fibrils. Conversely, insulin inhibited activation of NADPH oxidase and reduced intracellular levels of reactive oxygen species in LPS-treated BV2 cells.Conclusion: Insulin enhances microglial immune competence when challenged by endotoxins but mitigates oxidative stress in these cells. Keywords: β-amyloid, p47phox, phagocytosis, superoxide dismutase

Bo-Chieh Chang,1 Meng-Hsuan Kuo,1 Chi-Hui Lee,1 Ya-Lan Chu,1 Kuang-Peng Chen,2 Chun-Liong Tung,2 Ya-Hui Yang,3 Chuan-Sheng Hung,4 Jui-Hsiu Tsai,2,5 Hung-Yi Chuang6 1Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; 2Department of Psychiatry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; 3Department of Long-Term Care and Health Management, Cheng Shiu University, Kaohsiung, Taiwan; 4Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5School of Medicine, Tzu Chi University, Hualien, Taiwan; 6Department of Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Jui-Hsiu Tsai, Department of Psychiatry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Min-Sheng Road, Dalin Town, Chiayi, 622, Taiwan, Email faanvangogh@gmail.comIntroduction: Poor adherence to antipsychotics in patients with schizophrenia is a leading cause of relapse and functional deterioration. Long-acting injectable paliperidone may reduce relapse risks, health-care utilisation, and health-care costs in these patients.Methods: In this 24-month mirror-image study, we compared health-care utilization and costs before and after the initiation of paliperidone palmitate 3-monthly (PP3M) treatment in patients with schizophrenia spectrum disorders. Before the initiation of PP3M, the patients received paliperidone 1-monthly (PP1M) treatment. The primary study outcomes were changes in health-care utilisation and costs over the study period.Results: This study included 34 patients with schizophrenia spectrum disorders. During the 12-months period after the initiation of PP3M treatment, the mean duration of hospitalisation decreased from 57.7 to 28.5 days (p = 0.03). Moreover, significant reductions were noted in emergency room visits (PP1M vs PP3M: 0.3 vs 0.0, respectively; p = 0.05) and health-care costs (PP1M vs PP3M: 107,328.8 vs 57,848.6, respectively; p = 0.03).Conclusion: PP3M may significantly reduce hospitalisation duration, emergency room visits, and health-care costs in patients with schizophrenia.Keywords: schizophrenia, long-acting injectable antipsychotics, paliperidone palmitate, health-care cost, health-care utilisation

Chern-Horng Lee,1 Cheng-Li Lin,2 Tzung-Hai Yen,3 Sen-Yung Hsieh4,5 1Department of Geriatric Medicine and General Internal Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; 2Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; 3Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; 4Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; 5College of Medicine, Chang Gung University, Taoyuan, TaiwanCorrespondence: Sen-Yung Hsieh, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, 333, Taiwan, Tel +886-975368031, Fax +886-33272324, Email siming.shia@msa.hinet.net; siming@cgmh.org.twPurpose: Aspirin, known to reduce the risk of liver cancer, has been proposed as a preventive measure for patients with chronic hepatitis and cirrhosis. However, concerns regarding aspirin’s potential to cause gastrointestinal (GI) mucosal injury and bleeding have emerged. Several antiplatelets other than aspirin (APOA) that pose a smaller risk of GI bleeding than aspirin have been proposed as potential aspirin substitutes. This study investigated whether APOAs were effective at reducing the risk of hepatocellular carcinoma (HCC). Additionally, we evaluated the safety of APOAs, specifically regarding their potential to increase the risk of GI bleeding, in a nationwide cirrhosis cohort.Patients and Methods: For the period January 1, 2000, to December 31, 2017, we identified 686 993 patients with cirrhosis from a national database. A control group was established using 1:2 propensity score matching on the basis of sex, age, comorbidities, and medication use.Results: Daily use of APOAs was significantly associated with lower incidences of HCC (aHR 0.67; 95% CI, 0.60– 0.73; P < 0.001) and showed no significant increase in GI bleeding risk (aHR 1.04; 95% CI, 0.93– 1.15; P = 0.533) compared to nonuse of APOAs. However, the risks of intracranial hemorrhage (aHR, 1.41; 95% CI, 1.18 to 1.69; P < 0.001) and overall mortality (aHR, 2.03; 95% CI, 1.95 to 2.10; P < 0.001) were higher in the APOA user group.Conclusion: Our results suggest that although daily use of APOAs other than aspirin may decrease the HCC risk of patients with cirrhosis, it may also increase their risks of intracranial hemorrhage and overall mortality. Therefore, the use of APOAs as an alternative to aspirin for HCC prevention in patients with cirrhosis requires careful consideration.Keywords: cirrhosis, antiplatelet agents, hepatocellular carcinoma, intracranial hemorrhage, mortality

Clasina Leslie Smith,1,2,&ast; Bill Reddy,3,&ast; Charis M Wolf,4,5,&ast; Rosa N Schnyer,6,7,&ast; Korina St John,8,&ast; Lisa Conboy,4,7,9– 14,&ast; Jen Stone,15 Lixing Lao16– 18 1Chicago Healing Center, Chicago, IL, USA; 2School of Medicine, Southern Illinois University, Springfield, IL, USA; 3Vital Point Acupuncture, Annandale, VA, USA; 4Seattle Institute of East Asian Medicine, Seattle, WA, USA; 5Middle Way Acupuncture Institute, Seattle, WA, USA; 6School of Nursing, University of Texas, Austin, TX, USA; 7Oregon College of Oriental Medicine, Portland, OR, USA; 8Modern Medicine Woman, LLC, Palmer, AK, USA; 9Beth Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; 10California Institute of Integral Studies, San Francisco, CA, USA; 11Pacific College of Oriental Medicine, San Diego, CA, USA; 12YoSan University, Los Angeles, CA, USA; 13Five Branches University, Santa Cruz, CA, USA; 14American Academy of Health and Wellness, Roseville, MN, USA; 15CTSI, Indiana University School of Medicine, Indianapolis, IN, USA; 16Virginia University of Integrative Medicine, Vienna, VA, USA; 17School of Medicine, University of Maryland, Baltimore, MD, USA; 18School of Chinese Medicine, University of Hong Kong, Pokfulam, Hong Kong&ast;These authors contributed equally to this workCorrespondence: Clasina Leslie Smith, Chicago Healing Center, 1560 N Sandburg Ter, Unit 3215, Chicago, IL, 60610, USA, Tel +1-773-217-0567, Email LeslieTCM@gmail.comAbstract: The term “acupuncture” commonly refers to a non-pharmacologic therapy that is increasingly employed by diverse segments of the population for a wide variety of complaints including pain, insomnia, anxiety, depression, frozen shoulder, and other issues. The term is also used as a short-hand for the wider medical system from which the placement of needles into the skin for therapeutic benefit and related techniques evolved. Thus “acupuncture” refers both to the therapeutic technique and the therapeutic system of Acupuncture and Herbal Medicine (AHM). The other modalities included within AHM include a wide variety of physical and mechanical manipulations, herbal medicines, dietary recommendations, and lifestyle modifications. Clinically, acupuncture is increasingly offered in a variety of conventional medical settings such as hospitals, medical school clinics, veterans’ healthcare centers, oncology facilities, and rehabilitation centers, and its safety profile is excellent overall. Barriers to further incorporation of acupuncture into biomedical sites include insurance coverage of acupuncture, education of conventional medical practitioners and other stakeholders about the utility, efficacy, and evidence base of acupuncture. Acupuncturists in the United States are skilled practitioners who are highly educated in the complex therapeutic system from which acupuncture arose and in the technical aspects of its utility as a treatment modality. The training, certification, licensure, and regulation of acupuncturists is similar to that of conventional providers such has physician’s assistants, advanced practice nurses, and medical and osteopathic doctors. While clinical use and acceptance of acupuncture continues to grow, there is to date no definitive composite document explaining the utility of acupuncture in various healthcare settings, the current understanding of how acupuncture works, and the training, professional regulation, and certification of acupuncture practitioners. This article will address these topics and strive to create a reference for practitioners, administrators, legislators, insurance providers, patients and their families, and other stakeholders.Plain Language Summary: Acupuncture refers to the placement of thin, sterile needles into the skin to stimulate healing effects, and, in the United States, it also refers to the medical system from which the technique of acupuncture evolved. That system, Acupuncture and Herbal Medicine (AHM), uses acupuncture, dietary and lifestyle advice, herbal medicines, and other therapies to facilitate health and healing. Acupuncture is increasingly being used for a wide variety of medical problems including pain, difficulty sleeping, mental health concerns, and other issues in a wide variety of settings and is supported by a growing scientific basis for understanding why and how it works. Training and licensure of acupuncturists are similar to many conventional practitioners, and the process is accredited and overseen by various governmental and regulatory bodies. This paper aims to provide an overview of the use of acupuncture in the United States, the scientific basis for acupuncture, the training and licensure of acupuncturists, and the ways in which acupuncture is and might be incorporated into conventional medical settings.Keywords: acupuncture, herbal medicine, traditional Chinese medicine, integrative medicine, integrative health, medical policy

Chioma Laura Odimegwu,1 Samuel Nkachukwu Uwaezuoke,1 Ugo N Chikani,1 Ngozi Rita Mbanefo,1 Ken Daberechi Adiele,1 Charles Emeka Nwolisa,2 Chizoma Ihuarula Eneh,3 Chibuzo Obiora Ndiokwelu,1 Somkenechi C Okpala,1 Francis N Ogbuka,3 Kenneth E Odo,1 Ijeoma Onyinyechukwu Ohuche,1 Chinelo Elizabeth Obiora-Izuka1 1Department of Pediatrics, the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla Enugu, Nigeria; 2Department of Pediatrics, Federal University Teaching Hospital, Owerri, Nigeria; 3Department of Pediatrics, Enugu State University Teaching Hospital (ESUTH), Enugu, NigeriaCorrespondence: Samuel Nkachukwu Uwaezuoke, Department of Pediatrics, UNTH, Ituku-Ozalla Enugu, Nigeria, Tel +234 8033248108, Email samuel.uwaezuoke@unn.edu.ngAbstract: Although genetic, environmental, and lifestyle factors largely contribute to type 2 diabetes mellitus (T2DM) risk, the role of epigenetics in its pathogenesis is now well established. The epigenetic mechanisms in T2DM mainly consist of DNA methylation, histone modifications and regulation by noncoding RNAs (ncRNAs). For instance, DNA methylation at CpG islands in the promoter regions of specific genes encoding insulin signaling and glucose metabolism suppresses these genes. Modulating the enzyme mediators of these epigenetic marks aims to restore standard gene expression patterns and improve glycemic control. In targeting these epigenetic marks, using epigenetic drugs such as DNA methyltransferase (DNAMT), histone deacetylase (HDAC) and histone acetyltransferase (HAT) inhibitors has led to variable success in humans and experimental murine models. Specifically, the United States’ Food and Drug Administration (US FDA) has approved DNAMT inhibitors like 5-azacytidine and 5-aza-2ʹ-deoxycytidine for use in diabetic retinopathy: a T2DM microvascular complication. These DNAMT inhibitors block the genes for methylation of mitochondrial superoxide dismutase 2 (SOD2) and matrix metallopeptidase 9 (MMP-9): the epigenetic marks in diabetic retinopathy. Traditional pharmacotherapy with metformin also have epigenetic effects in T2DM and positively alter disease outcomes when combined with epigenetic drugs like DNAMT and HDAC inhibitors, raising the prospect of using epigenetic therapy as a valuable adjunct to pharmacotherapy. However, introducing small interfering RNAs (siRNAs) in cells to silence specific target genes remains in the exploratory phase. Future research should focus on regulating gene expression in T2DM using long noncoding RNA (lncRNA) molecules, another type of ncRNA. This review discusses the epigenetics of T2DM and that of its macro- and microvascular complications, and the potential benefits of combining epigenetic therapy with pharmacotherapy for optimal results.Keywords: type 2 diabetes mellitus, epigenetics, DNA methylation, histone modifications, noncoding RNA regulation, therapeutics, epigenetic therapy

Introduction: Hyponatremia is a common electrolyte disorder in hospitalized patients and has been linked to increased morbidity and mortality in various clinical settings. Patients with ST-elevation myocardial infarction (STEMI) are at risk of developing hyponatremia due to complex interplay of pathophysiological mechanisms. This study aimed to investigate the prevalence, risk factors, and prognostic value of hyponatremia in patients with STEMI. Materials and Methods: This was a retrospective study of 192 patients with STEMI who were admitted to a tertiary care hospital between July 2021 and December 2021. Patients were divided into two groups based on their serum sodium levels during hospitalization: Hyponatremia group (serum sodium

Xi Cao,1 Yong-Li Xie,2,3 Jian-Ying Yi,1 Zhi-Li Liu,4 Meng Han,1 Ji-hui Duan,1 Qiang Gao,1 Hong Mu,1 Chun-lei Zhou1 1Department of Clinical Laboratory, Tianjin First Central Hospital, Tianjin, People’s Republic of China; 2Department of Clinical Laboratory, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, People’s Republic of China; 3Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, People’s Republic of China; 4Department of Clinical Laboratory, the Third Central Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Hong Mu; Chun-lei Zhou, Department of Clinical Laboratory, Tianjin First Central Hospital, Tianjin, People’s Republic of China, Email mutjyzxyy@163.com; tj_zcl@hotmail.comPurpose: The emergence of the SARS-CoV-2 Omicron variant has posed a significant global public health challenge. Elucidating the laboratory profiles of individuals infected with this variant is crucial for assessing organ damage. This study aimed to investigate the variations in liver function tests and their correlation with demographic characteristics and inflammatory markers in patients with early Omicron variant infections.Patients and Methods: A retrospective cohort study was conducted on 1133 mild or asymptomatic COVID-19 cases at Tianjin First Central Hospital. Data on age, gender, body mass index (BMI), and serum markers were collected and analyzed. Statistical analyses were performed using SPSS software, version 24.0.Results: Abnormal liver function parameters, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (TBIL), were observed in 314 (27.71%) patients. “Hepatocellular type” was identified in 56 (4.94%) patients, “cholestatic type” in 185 (16.33%) patients, and “mixed type” in 73 (6.44%) patients. In the mixed group, we observed a pronounced elevation in the levels of ALT, AST, and GGT. Moreover, the hepatocellular group exhibited a statistically significant increase in AST and ALT concentrations relative to both the normal and cholestatic groups. Notably, the cholestatic group demonstrated a substantial increment in ALP levels. Males had a significantly higher prevalence of “abnormal liver enzyme markers” compared to females. Patients with “abnormal liver enzyme markers” exhibited significantly decreased immunoglobulin G (IgG) levels and elevated levels of inflammatory markers, including procalcitonin (PCT), interleukin-6 (IL6), as well as C-reactive protein (CRP) compared to normal group. Logistic regression analysis revealed that male gender and PCT levels were significantly associated with the risk of abnormal liver enzyme markers. Patients in hepatocellular group were likely accompanied with high CRP levels, whereas those in the cholestatic type were associated with high IL6 levels.Conclusion: Early Omicron infection might cause liver stress response. Elevated liver enzyme marker levels were correlated with age, gender, inflammatory factors, and IgG.Keywords: Omicron variant, “abnormal liver enzyme markers”, male, inflammatory markers

John C Coffman,1 Justin Jones,2 Nasir Hussain,1 Mahmoud Abdel-Rasoul,3 Peter W Dienhart,1 Samiha M Nasser,1 Charles L Hamilton III,1 Jonathan A Lipps,1 Michael Kushelev1 1Department of Anesthesiology, The Ohio State University, Columbus, OH, USA; 2Department of Anesthesiology and Pain Management, The Metrohealth System, Cleveland, OH, USA; 3Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USACorrespondence: John C Coffman, Department of Anesthesiology, The Ohio State University, 410 W. 10th Ave, Columbus, OH, 43210, USA, Tel +1 614 293 8487, Email john.coffman@osumc.eduIntroduction: Hip arthroscopy is commonly performed as an outpatient procedure and effective postoperative pain management is important to provide quality patient care and enable timely discharge. Multiple regional nerve blocks have been described for pain relief after hip arthroscopy, but there is no consensus on the optimal technique. This retrospective investigation aimed to compare quadratus lumborum (QL) and pericapsular nerve group (PENG) blocks to determine if there are differences in analgesic outcomes after outpatient hip arthroscopy.Methods: A total of 50 consecutive patients that received QL block and 50 that received PENG block for outpatient hip arthroscopy were identified and compared to determine if there were any differences in the primary outcome of total perioperative opioid consumption prior to discharge from the surgery center. Important secondary analgesic outcomes include postoperative opioid consumption, verbal rating scale (VRS) pain scores or total time in the recovery area. Summary statistics of relevant variables are compared and reported between study groups (QL versus PENG).Results: For QL and PENG groups, no significant differences were observed in total perioperative oral morphine equivalents (OME) (69.5 vs 60mg; p=0.40), postoperative OME (15 vs 15.3mg; p=0.96) or maximum pain scores in the recovery area (7.0 vs 6.0; p=0.41). Postoperatively, QL block patients were in PACU for a greater length of time after surgery than PENG block patients (89.5 vs 72 minutes; p< 0.001). No patients had uncontrolled pain requiring emergency room visits or hospital admission within 24 hours. No neurologic complications or instances of motor weakness were reported after QL or PENG blocks.Conclusion: This retrospective study observed similar opioid requirements and pain scores for patients receiving QL versus PENG block for hip arthroscopy, though PENG block patients had shorter times in the recovery area. Prospective, controlled trials are required to further explore and confirm these findings.Keywords: quadratus lumborum, QL, pericapsular nerve group, PENG, Hip arthroscopy

Abstract The WHO recently published a Tobacco Knowledge Summary (TKS) synthesizing current evidence on tobacco and COPD, aiming to raise awareness among a broad audience of health care professionals. Furthermore, it can be used as an advocacy tool in the fight for tobacco control and prevention of tobacco-related disease. This article builds on the evidence presented in the TKS, with a greater level of detail intended for a lung-specialist audience. Pulmonologists have a vital role to play in advocating for the health of their patients and the wider population by sharing five key messages: (1) Smoking is the leading cause of COPD in high-income countries, contributing to approximately 70% of cases. Quitting tobacco is an essential step toward better lung health. (2) People with COPD face a significantly higher risk of developing lung cancer. Smoking cessation is a powerful measure to reduce cancer risk. (3) Cardiovascular disease, lung cancer and type-2 diabetes are common comorbidities in people with COPD. Quitting smoking not only improves COPD management, but also reduces the risk of developing these coexisting conditions. (4) Tobacco smoke also significantly impacts children’s lung growth and development, increasing the risk of respiratory infections, asthma and up to ten other conditions, and COPD later in life. Governments should implement effective tobacco control measures to protect vulnerable populations. (5) The tobacco industry’s aggressive strategies in the marketing of nicotine delivery systems and all tobacco products specifically target children, adolescents, and young adults. Protecting our youth from these harmful tactics is a top priority.

We present a sample-variance-limited measurement of the temperature power spectrum (TT) of the cosmic microwave background using observations of a ∼1500 deg2 field made by the SPT-3G in 2018. We report multifrequency power spectrum measurements at 95, 150, and 220 GHz covering the angular multipole range 750≤ℓ

ImportanceNeuropsychiatric symptoms are commonly encountered and are highly debilitating in patients with Alzheimer disease. Understanding their underpinnings has implications for identifying biomarkers and treatment for these symptoms.ObjectiveTo evaluate whether glial markers are associated with neuropsychiatric symptoms in individuals across the Alzheimer disease continuum.Design, setting, and participantsThis cross-sectional study was conducted from January to June 2023, leveraging data from the Translational Biomarkers in Aging and Dementia cohort at McGill University, Canada. Recruitment was based on referrals of individuals from the community or from outpatient clinics. Exclusion criteria included active substance abuse, major surgery, recent head trauma, safety contraindications for positron emission tomography (PET) or magnetic resonance imaging, being currently enrolled in other studies, and having inadequately treated systemic conditions.Main outcomes and measuresAll individuals underwent assessment for neuropsychiatric symptoms (Neuropsychiatry Inventory Questionnaire [NPI-Q]), and imaging for microglial activation ([11C]PBR28 PET), amyloid-β ([18F]AZD4694 PET), and tau tangles ([18F]MK6240 PET).ResultsOf the 109 participants, 72 (66%) were women and 37 (34%) were men; the median age was 71.8 years (range, 38.0-86.5 years). Overall, 70 had no cognitive impairment and 39 had cognitive impairment (25 mild; 14 Alzheimer disease dementia). Amyloid-β PET positivity was present in 21 cognitively unimpaired individuals (30%) and in 31 cognitively impaired individuals (79%). The NPI-Q severity score was associated with microglial activation in the frontal, temporal, and parietal cortices (β = 7.37; 95% CI, 1.34-13.41; P = .01). A leave-one-out approach revealed that irritability was the NPI-Q domain most closely associated with the presence of brain microglial activation (β = 6.86; 95% CI, 1.77-11.95; P = .008). Furthermore, we found that microglia-associated irritability was associated with study partner burden measured by NPI-Q distress score (β = 5.72; 95% CI, 0.33-11.10; P = .03).Conclusions and relevanceIn this cross-sectional study of 109 individuals across the AD continuum, microglial activation was associated with and a potential biomarker of neuropsychiatric symptoms in Alzheimer disease. Moreover, our findings suggest that the combination of amyloid-β- and microglia-targeted therapies could have an impact on relieving these symptoms.

COVID-19 is a disease of dysfunctional immune responses, but the mechanisms triggering immunopathogenesis are not established. The functional plasticity of macrophages allows this cell type to promote pathogen elimination and inflammation or suppress inflammation and promote tissue remodeling and injury repair. During an infection, the clearance of dead and dying cells, a process named efferocytosis, can modulate the interplay between these contrasting functions. Here, we show that engulfment of SARS-CoV-2-infected apoptotic cells exacerbates inflammatory cytokine production, inhibits the expression of efferocytic receptors, and impairs continual efferocytosis by macrophages. We also provide evidence supporting that lung monocytes and macrophages from severe COVID-19 patients have compromised efferocytic capacity. Our findings reveal that dysfunctional efferocytosis of SARS-CoV-2-infected cell corpses suppresses macrophage anti-inflammation and efficient tissue repair programs and provides mechanistic insights for the excessive production of pro-inflammatory cytokines and accumulation of tissue damage associated with COVID-19 immunopathogenesis.

Optomotor responses are a popular way to assess sub-cortical visual responses in mice. We studied photoreceptor inputs into optomotor circuits using genetically-modified mice lacking the exocytotic calcium sensors synaptotagmin 1 (Syt1) and 7 (Syt7) in rods or cones. We also tested mice that in which cone transducin, GNAT2, had been eliminated. We studied spatial frequency sensitivity under mesopic conditions by varying the spatial frequency of a grating rotating at 12 deg/s and contrast sensitivity by varying luminance contrast of 0.2c/deg gratings. We found that eliminating Syt1 from rods reduced responses to a low spatial frequency grating (0.05c/deg) consistent with low resolution in this pathway. Conversely, eliminating the ability of cones to respond to light (by eliminating GNAT2) or transmit light responses (by selectively eliminating Syt1) showed weaker responses to a high spatial frequency grating (3c/deg). Eliminating Syt7 from the entire optomotor pathway in a global knockout had no significant effect on optomotor responses. We isolated the secondary rod pathway involving transmission of rod responses to cones via gap junctions by simultaneously eliminating Syt1 from rods and GNAT2 from cones. We found that the secondary rod pathway is sufficient to drive robust optomotor responses under mesopic conditions. Finally, eliminating Syt1 from both rods and cones almost completely abolished optomotor responses, but we detected weak responses to large, bright rotating gratings that are likely driven by input from intrinsically photosensitive retinal ganglion cells.

We cross-correlate positions of galaxies measured in data from the first three years of the Dark Energy Survey with Compton-y maps generated using data from the South Pole Telescope (SPT) and the Planck mission. We model this cross-correlation measurement together with the galaxy autocorrelation to constrain the distribution of gas in the Universe. We measure the hydrostatic mass bias or, equivalently, the mean halo bias-weighted electron pressure (bh Pe), using large-scale information. We find (bh Pe) to be [0.16+−000403, 0.28+−000504, 0.45+−001006, 0.54+−000708, 0.61+−000608, 0.63+−000807] meV cm−3 at redshifts z ∼ [0.30, 0.46, 0.62, 0.77, 0.89, 0.97]. These values are consistent with previous work where measurements exist in the redshift range. We also constrain the mean gas profile using small-scale information, enabled by the high-resolution of the SPT data. We compare our measurements to different parametrized profiles based on the cosmo-OWLS hydrodynamical simulations. We find that our data are consistent with the simulation that assumes an AGN heating temperature of 108.5 K but are incompatible with the model that assumes an AGN heating temperature of 108.0 K. These comparisons indicate that the data prefer a higher value of electron pressure than the simulations within r500c of the galaxies’ haloes.

Abstract Including millimeter-wave data in multiwavelength studies of the variability of active galactic nuclei (AGN) can provide insights into AGN physics that are not easily accessible at other wavelengths. We demonstrate in this work the potential of cosmic microwave background (CMB) telescopes to provide long-term, high-cadence millimeter-wave AGN monitoring over large fractions of sky. We report on a pilot study using data from the SPTpol instrument on the South Pole Telescope (SPT), which was designed to observe the CMB at arcminute and larger angular scales. Between 2013 and 2016, SPTpol was used primarily to observe a single 500 deg2 field, covering the entire field several times per day with detectors sensitive to radiation in bands centered at 95 and 150 GHz. We use SPT 150 GHz observations to create AGN light curves, and we compare these millimeter-wave light curves to those at other wavelengths, in particular γ-ray and optical. In this Letter, we focus on a single source, PKS 2326-502, which has extensive, day-timescale monitoring data in gamma-ray, optical, and now millimeter-wave between 2013 and 2016. We find PKS 2326-502 to be in a flaring state in the first 2 yr of this monitoring, and we present a search for evidence of correlated variability between millimeter-wave, optical R-band, and γ-ray observations. This pilot study is paving the way for AGN monitoring with current and upcoming CMB experiments such as SPT-3G, Simons Observatory, and CMB-S4, including multiwavelength studies with facilities such as Vera C. Rubin Observatories Large Synoptic Survey Telescope.

Matthew Slitzky,1 R Jason Yong,2 Giuliano Lo Bianco,3 Trent Emerick,4 Michael E Schatman,5,6 Christopher L Robinson2 1Burke Rehabilitation, Montefiore Health System, White Plains, NY, USA; 2Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA; 3Anesthesiology and Pain Department, Fondazione Istituto G. Giglio Cefalù, Palermo, Italy; 4Department of Anesthesiology and Perioperative Medicine, Chronic Pain Division, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 5Department of Anesthesiology, Perioperative Care, and Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 6Department of Population Health-Division of Medical Ethics, NYU Grossman School of Medicine, New York, NY, USACorrespondence: Christopher L Robinson, Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Brigham and Women’s Hospital, 75 Francis Street Boston, Boston, MA, 02118, USA, Email crobinson48@bwh.harvard.edu

Yi-Rong Lin,1 Wu-Chou Lin,1,2 Mei-Yao Wu,3– 5 Cheng-Li Lin,6 Su-Tso Yang,1,7,&ast; Hung-Rong Yen1,4,5,8,&ast; 1Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 404, Taiwan; 2Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, 404, Taiwan; 3School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 404, Taiwan; 4Department of Chinese Medicine, China Medical University Hospital, Taichung, 404, Taiwan; 5Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, 404, Taiwan; 6Management Office for Health Data, China Medical University Hospital, Taichung, 404, Taiwan; 7Department of Radiology, China Medical University Hospital, Taichung, 404, Taiwan; 8Chinese Medicine Research Center, China Medical University, Taichung, 404, Taiwan&ast;These authors contributed equally to this workCorrespondence: Hung-Rong Yen, School of Chinese Medicine, College of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, North District, Taichung, 404328, Taiwan, Tel +886-4-22053366 ext. 3001, Fax +886-4-22365141, Email hungrongyen@mail.cmu.edu.tw Su-Tso Yang, Department of Radiology, China Medical University Hospital, 2 Yude Road, North District, Taichung, 404327, Taiwan, Tel +886-4-22052121 ext. 5470, Fax +886-4-22365141, Email yangst@mail.cmu.edu.twBackground: Many patients with dysfunctional uterine bleeding (DUB) seek traditional medicine consultations. This study intended to investigate the association of complementary Chinese herbal medicine (CHM) with the surgery rate in patients with DUB in Taiwan.Methods: We enrolled 43,027 patients with newly diagnosed DUB (ICD-9-CM codes 626.8) from the National Health Insurance Research Database in Taiwan during the period of 1997 to 2010. Among them, 38,324 were CHM users, and 4703 did not receive CHM treatment. After performing a 1:1 propensity-score match based on patients’ age (per 5 years), comorbidities, conventional drugs, childbirth status, duration from the diagnosis year of DUB and index year, there were an equal number (n=4642) of patients in the CHM cohort and non-CHM cohort. The outcome measurement was the comparison of incidences of surgical events, including hysterectomy and endometrial ablation, in the two cohorts before the end of 2013.Results: CHM users had a lower incidence of surgery than non-CHM users (adjusted HR 0.27, 95% CI: 0.22– 0.33). The cumulative incidence of surgery was significantly lower in the CHM cohort during the follow-up period (Log rank test, p < 0.001). A total of 146 patients in the CHM cohort (4.99 per 1000 person-years) and 485 patients in the non-CHM cohort (20.19 per 1000 person-years) received surgery (adjusted HR 0.27, 95% CI: 0.22– 0.33). CHM also reduced the risk of surgery in DUB patients with or without comorbidities. Regardless of childbirth status or whether patients took NSAIDs, tranexamic acid or progesterone, fewer patients in the CHM cohort underwent surgery than in the non-CHM cohort. The most commonly prescribed single herb and formula were Yi-Mu-Cao (Herba Leonuri) and Jia-Wei-Xiao-Yao-San, respectively.Conclusion: The real-world data revealed that CHM is associated with a reduced surgery rate in DUB patients. This information may be provided for further clinical investigations and policy-making.Keywords: complementary and alternative medicine, Chinese herbal medicine, dysfunctional uterine bleeding, hysterectomy, National Health Insurance Research Database, surgery

Abstract Background Psychiatric emergency assessment of minors can be a complex process, especially for professional staff who are not specifically trained in handling child and adolescent emergency patients. As minors cannot usually express their feelings and experiences as well as adults, it is difficult to form an accurate picture of their condition and to determine what kind of emergency care is needed, for instance whether or not a psychiatric emergency admission is necessary. We lack insight in what professionals at emergency departments need to adequately assess these minors and their families. The aim of this study was to explore staff members’ experiences with assessing minors and explore recommendations for improving their ability to provide appropriate support. Methods Guided by a topic list with open-ended questions, we conducted 11 semi-structured interviews with staff working at psychiatric emergency services. Thematic analysis enabled us to identify five main themes: (1) young age and the crucial role of parents; (2) professionals’ feelings, especially uncertainty; (3) psychiatric emergency admissions and the alternatives to them; (4) regional differences in organization and tasks; and (5) options for improving care. Results The staff interviewed all agreed that it was often complicated and time consuming to take full responsibility when assessing minors with serious and urgent psychiatric problems. Most found it difficult to determine which behaviors were and were not age-appropriate, and how to handle systemic problems during the assessment. When assessing minors and their families in crisis, this led to uncertainty. Professionals were especially insecure when assessing children under age 12 and their families, feeling they lacked the appropriate knowledge and routine. Conclusion Customized expertise development and improved regional embedding of the psychiatric emergency service in the child and adolescent services will reduce professionals’ uncertainty and improve psychiatric emergency care for minors.

Introduction: The Malaysian Orthopaedic Journal (MOJ) (ISSN 1985-2533 / 2232-111X) is the official publication of the Malaysian Orthopaedic Association (MOA) and the ASEAN Orthopaedic Association (AOA). In May 2007, MOA published the first standalone issue of MOJ with the aim of disseminating new knowledge and providing updates in orthopaedics, trauma and musculoskeletal research. Since then, MOJ has grown significantly, achieving indexing in numerous databases and attaining a 2nd Quartile (Q2) rank in the Scopus database in 2022. This bibliometric analysis aims to explore the trends and distribution of articles published in MOJ. Materials and methods: Bibliometric data for MOJ was extracted from the SCOPUS database, covering the years from its indexing to 2022. Information such as authors, country, document type, author’s keywords, citations, and other parameters were extracted using the bibliometrix package in the R Studio software. The data were then presented in tables and illustrative graphs using the same software. Results: A total of 305 articles were retrieved from the Scopus database during the study period. Two-thirds of the articles were original articles and review articles. The highest number of citations received by an article is 56, and top ten articles in MOJ were authored by researchers from seven different countries, highlighting the journal’s diversity. Despite receiving submissions from various countries, there is minimal collaboration between authors of different countries. Keywords such as “covid-19” and “pandemic” dominate the authors’ keyword section due to the once-in-a-life-time COVID-19 which during the study period, resulting in numerous publications related to this issue. Conclusion: This bibliometric analysis reviews all the articles indexed in the Scopus database and provides insight into the contributors’ information and the trends in orthopaedic research. By identifying the lack of collaboration between countries, it is hoped that this analysis can inspire more orthopaedic surgeons and researchers to collaborate and produce high-quality publications.

Chenkun Wang,1,2,&ast; Jing Gu,2,&ast; Hongwei Li,2,&ast; Bo Zhao,2 Tao Yu,1,2 Chun-Ling Guo,2 Mouxin Huang,2 Weiwei Jiang,1 Qin Ouyang2 1Department of Pharmacy, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Medicinal Chemistry, College of Pharmacy, Third Military Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiwei Jiang, Department of Pharmacy, the Second Affiliated Hospital, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400010, People’s Republic of China, Email 304035@cqmu.edu.cn Qin Ouyang, Department of Medicinal Chemistry, College of Pharmacy, Third Military Medical University, No. 30 Gaotanyan St., Shapingba District, Chongqing, 400038, People’s Republic of China, Email ouyangq@tmmu.edu.cnBackground and Objective: GIT1 (G-protein-coupled receptor kinase interacting protein-1) has been found to be highly related with cancer cell invasion and metastasis in many cancer types. β-Pix (p21-activated kinase-interacting exchange factor) is one of the proteins that interact with GIT1. Targeting GIT1/β-Pix complex might be a potential therapeutic strategy for interfering cancer metastasis. However, at present, no well-recognized small-molecule inhibitor targeting GIT1/β-Pix is available. Thus, we aim to discover novel GIT1/β-Pix inhibitors with simple scaffold, high activity and low toxicity to develop new therapeutic strategies to restrain cancer metastasis.Methods: GIT1/β-Pix inhibitors were identified from ChemBridge by virtual screening. Briefly, the modeling of GIT1 was performed and the establishment of GIT1/β-Pix binding pocket enabled the virtual screening to identify the inhibitor. In addition, direct binding of the candidate molecules to GIT1 was detected by biolayer interferometry (BLI) to discover the hit compound. Furthermore, the inhibitory effect on invasion of stomach and colon cancer cells in vitro was carried out by the transwell assay and detection of epithelial-mesenchymal transition (EMT)-related proteins. Finally, the binding mode of hit compound to GIT1 was estimated by molecular dynamics simulation to analyze the key amino residues to guide further optimization.Results: We selected the top 50 compounds from the ChemBridge library by virtual screening. Then, by skeleton similarity analysis nine compounds were selected for further study. Furthermore, the direct interaction of nine compounds to GIT1 was detected by BLI to obtain the best affinitive compound. Finally, 17302836 was successfully identified (KD = 84.1± 2.0 μM). In vitro tests on 17302836 showed significant anti-invasion effect on gastric cancer and colorectal cancer.Conclusion: We discovered a new GIT1/β-Pix inhibitor (17302836) against gastrointestinal cancer invasion and metastasis. This study provides a promising candidate for developing new GIT1/β-Pix inhibitors for tumor treatment.Keywords: hit discovery, virtual screening, GIT1, β-Pix, gastrointestinal cancers, invasion

Ming-Jr Jian,1,&ast; Tai-Han Lin,1,&ast; Hsing-Yi Chung,1,2 Chih-Kai Chang,1 Cherng-Lih Perng,1 Feng-Yee Chang,3 Hung-Sheng Shang1 1Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 2Graduate Institute of Medical Science, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 3Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan, Republic of China&ast;These authors contributed equally to this workCorrespondence: Hung-Sheng Shang, Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, No. 161, Sec. 6, Minquan E. Road, Neihu District, Taipei City, 11490, Taiwan, Republic of China, Tel +886920713130, Email iamkeith001@gmail.comPurpose: The World Health Organization has identified Klebsiella pneumoniae (KP) as a significant threat to global public health. The rising threat of carbapenem-resistant Klebsiella pneumoniae (CRKP) leads to prolonged hospital stays and higher medical costs, necessitating faster diagnostic methods. Traditional antibiotic susceptibility testing (AST) methods demand at least 4 days, requiring 3 days on average for culturing and isolating the bacteria and identifying the species using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), plus an extra day for interpreting AST results. This lengthy process makes traditional methods too slow for urgent clinical situations requiring rapid decision-making, potentially hindering prompt treatment decisions, especially for fast-spreading infections such as those caused by CRKP. This research leverages a cutting-edge diagnostic method that utilizes an artificial intelligence-clinical decision support system (AI-CDSS). It incorporates machine learning algorithms for the swift and precise detection of carbapenem-resistant and colistin-resistant strains.Patients and Methods: We selected 4307 KP samples out of a total of 52,827 bacterial samples due to concerns about multi-drug resistance using MALDI-TOF MS and Vitek-2 systems for AST. It involved thorough data preprocessing, feature extraction, and machine learning model training fine-tuned with GridSearchCV and 5-fold cross-validation, resulting in high predictive accuracy, as demonstrated by the receiver operating characteristic and area under the curve (AUC) scores, laying the groundwork for our AI-CDSS.Results: MALDI-TOF MS analysis revealed distinct intensity profiles differentiating CRKP and susceptible strains, as well as colistin-resistant Klebsiella pneumoniae (CoRKP) and susceptible strains. The Random Forest Classifier demonstrated superior discriminatory power, with an AUC of 0.96 for detecting CRKP and 0.98 for detecting CoRKP.Conclusion: Integrating MALDI-TOF MS with machine learning in an AI-CDSS has greatly expedited the detection of KP resistance by approximately 1 day. This system offers timely guidance, potentially enhancing clinical decision-making and improving treatment outcomes for KP infections.Keywords: carbapenem, colistin, diagnostic accuracy, antibiotic stewardship, MALDI-TOF MS

Wen Jun Zhang,&ast; Chong Ling Hu,&ast; Bing Ling Guo, Xi Ping Liang, Chao Yu Wang, Tao Yang Department of Hematology Oncology, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Yang, Department of Hematology Oncology, Chongqing University Cancer Hospital, No. 181, Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Tel +86-13527363925, Email ppyangtao@163.comObjective: The purpose of this study was to analyze the mechanism by which STAT5B inhibits ferroptosis in mantle cell lymphoma (MCL) by promoting DCAF13 transcriptional regulation of p53/xCT pathway.Methods: The correlations between STAT5B, DCAF13 and ferroptosis in MCL were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA, http://gepia.cancer-pku.cn/index.html). The expression levels and pairwise correlations of STAT5B, DCAF13, p53 and xCT in MCL patients were detected, respectively. STAT5B was silenced to confirm their criticality in MCL ferroptosis. the effects of blocking necrosis, apoptosis and ferroptosis on the anti-MCL effects of STAT5B were examined. Cells with STAT5B overexpression and/or DCAF13 silencing were constructed to confirm the involvement of DCAF13 in the STAT5B-regulated p53/xCT pathway. The regulation of p53 ubiquitination was confirmed by DCAF13 overexpression and MG132. The effects of silencing DCAF13 and MG132 on STAT5B overexpression on MCL was clarified by a tumor-bearing nude mouse model.Results: DCAF13 was overexpressed in MCL and positively correlated with STAT5B, negatively correlated with p53, and positively correlated with xCT. Inhibition of ferroptosis alleviated the inhibitory effects of siSTAT5B on MCL, while inhibition of necrosis and apoptosis had few effects. Silencing of DCAF13 led to the blocking of STAT5B regulation of p53/xCT and ferroptosis. The changes in DCAF13 and the addition of MG132 did not have statistically significant effects on p53 mRNA. Elevation of DCAF13 resulted in downregulation of p53 protein levels, and this inhibition was reversed by MG132. In animal models, the promotion of MCL and the inhibition of ferroptosis by STAT5B. Silencing of DCAF13 blocked STAT5B inhibition of p53 and induction of xCT, GPX4, and GSH.Conclusion: STAT5B suppresses ferroptosis by promoting DCAF13 transcription to regulate p53/xCT pathway to promote MCL progression.Keywords: mantle cell lymphoma, STAT5B, DCAF13, ferroptosis

Chih-Ying Wu,1– 3 Li-Wei Chou,4– 6 Shih-Wei Huang,7 Wen-Ling Liao,1,8 Shiaw-Meng Chang,9 Han-Chung Lee,10 Cheng-Di Chiu,3,11– 14 Chih-Hsin Tang,13,15– 18 Ching-Liang Hsieh16,19,20 1Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; 2Department of Neurosurgery, China Medical University Hsinchu Hospital, China Medical University, Hsinchu, Taiwan; 3Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan; 4Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; 5Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; 6Department of Physical Medicine and Rehabilitation, Asia University Hospital, Asia University, Taichung, Taiwan; 7Department of Traditional Chinese Medicine, China Medical University Hsinchu Hospital, China Medical University, Hsinchu, Taiwan; 8Center for Personalized Medicine, China Medical University Hospital, Taichung, Taiwan; 9Department of Industrial Engineering and Engineering Management, National Tsing Hua University, Hsinchu, Taiwan; 10Neuroscience center, Everan Hospital, Taichung, Taiwan; 11Spine Center, China Medical University Hospital, Taichung, Taiwan; 12School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; 13Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan; 14Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; 15Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan; 16Chinese Medicine Research Center, China Medical University, Taichung, Taiwan; 17Department of Medical Laboratory Science and Biotechnology, College of Health Science, Asia University, Taichung, Taiwan; 18Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan; 19Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; 20Graduate Institute of Acupuncture Science, China Medical University, Taichung, TaiwanCorrespondence: Chih-Hsin Tang, Graduate Institute of Biomedical Science, College of Medicine, China Medical University, Taichung, 40402, Taiwan, Email chtang@mail.cmu.edu.tw Ching-Liang Hsieh, Graduate Institute of Acupuncture Science, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan, Tel +886-4-22053366, Fax +886-4-22037690, Email clhsieh0826@gmail.comBackground: Fu’s subcutaneous needling (FSN) is a novel acupuncture technique for pain treatment. This study investigated the effects of postsurgical FSN on postoperative pain in patients receiving surgery for degenerative spinal disorders.Methods: This single-center, single-blind, randomized-controlled study involved patients undergoing surgery for degenerative spinal disorders. Participants were randomized into either an FSN group or a control group that received sham FSN. The primary outcomes were scores on the Brief Pain Inventory Taiwan version (BPI-T) and Oswestry Disability Index before and at 1, 24, and 48 hours after surgery. Secondary outcomes were muscle hardness, pethidine use, and inflammatory biomarker presence.Results: Initially, 51 patients met the inclusion criteria and were allocated (26 in the FSN group and 25 in the control group). Two patients were lost to follow-up, and finally, 49 patients (25 in the FSN group and 24 in the control group) who completed the study were analyzed. The FSN group had significantly lower pain intensity measured on the BPI-T compared with the control group at 1, 24, 48, and 72 hours after surgical treatment (all p < 0.001). Additionally, pain interference as measured on the BPI-T was lower in the FSN group than in the control group 1 hour (p = 0.001), 24 hours (p = 0.018), 48 hours (p = 0.001), and 72 hours (p = 0.017) after surgical treatment. Finally, the FSN group exhibited less muscle hardness in the latissimus dorsi and gluteus maximus 24, 48, and 72 hours (all p < 0.05) after surgery compared with the control group; patients in the FSN group also exhibited less muscle hardness in the L3 paraspinal muscle 48 hours (p = 0.001) and 72 hours (p < 0.001) after surgery compared with the control group. There were no significant differences in serum CRP, IL-1β, IL-2, IL-6, and TNF-α levels between the FSN and control groups at 24 hours, 72 hours, and 1-month post-surgery (all p > 0.05).Conclusion: FSN treatment can reduce postoperative pain in patients receiving surgery for degenerative spinal disorders. However, larger sample sizes and multicenter clinical trials are required to verify these findings.Keywords: Fu’s subcutaneous needling, degenerative spinal disorders, postoperative pain, surgical treatment, clinical trial

Shih-Ching Chin,1,&ast; Yun-Hsuan Chang,2– 6,&ast; Chih-Chun Huang,6,7 Ting-Hsi Chou,1 Chieh-Liang Huang,8 Hsiu-Man Lin,9 Marc N Potenza10 1Department of Psychology, Asia University, Taichung, Taiwan; 2Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Psychology, National Cheng Kung University, Tainan, Taiwan; 5Institute of Genomics and Bioinformatics, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan; 6Department of Psychiatry, National Cheng Kung University Hospital, Douliou Branch, Yunlin, Taiwan; 7Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Psychiatry, Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nantou, Taiwan; 9Department of Child and Adolescent Development and Mental Health, China Medical University Children’s Hospital, Taichung, Taiwan; 10Psychiatry, Child Study and Neuroscience, Center of Excellence in Gambling Research, Yale School of Medicine, New Haven, CT, USA&ast;These authors contributed equally to this workCorrespondence: Yun-Hsuan Chang, Licensed Clinical Psychologist, Institute of Gerontology, College of Medicine; Department of Psychology, National Cheng Kung University, No. 1., University Road, Tainan, Taiwan, Email z11108051@ncku.edu.tw; yh.chang.snoopy@gmail.comIntroduction: The surge in mobile gaming, fueled by smartphone and internet accessibility, lacks a comprehensive understanding of physiological changes during gameplay.Methods: This study, involving 93 participants (average age 21.75 years), categorized them into Problematic Mobile Gaming (PMG) and non-problematic Mobile Gaming (nPMG) groups based on Problematic Mobile Gaming Questionnaire (PMGQ) scores. The PMGQ is a 12-item scale developed in Taiwan to assess symptoms of problematic mobile gaming. The research delved into heart rate variability (HRV) alterations during real-time mobile gaming and self-gaming video viewing.Results: Results showed that the PMG group significantly presents a lower root mean square of successive differences (RMSSD), and High Frequency (lnHF) than does the nPMG group (F=4.73, p=0.03; F=10.65, p=0.002, respectively) at the baseline. In addition, the PMG group significantly displayed elevated HF and low-frequency to high-frequency (LF/HF) in the mobile-gaming (F=7.59, p=0.007; F=9.31, p=0.003) condition as well as in the watching self-gaming videos (F=9.75, p=0.002; F=9.02, p=0.003) than did the nPMG.Conclusion: The study suggests targeted interventions to mitigate autonomic arousal, offering a potential avenue to address adverse effects associated with problematic mobile gaming behavior. The PMG group displayed increased craving scores after real-time mobile gaming and watching self-gaming video excerpts, unlike the nPMG group. Elevated LF/HF ratios in frequent gaming cases heightened autonomic arousal, presenting challenges in relaxation after mobile gaming. These findings contribute to a nuanced understanding of the complex interplay between mobile gaming activities, physiological responses, and potential intervention strategies.Keywords: addictive behaviors, video games, internet addiction, autonomic nervous system, craving, heart rate variability, self-regulation

Cristina-Mihaela Popescu,1 Virginia Marina,2 Georgiana Avram,3 Carmen Laura Cristescu Budala3 1Dental-Medicine Department, Faculty of Medicine and Pharmacy, “dun&abreve;rea de Jos” University, Galați, 800201, Romania; 2Medical Department of Occupational Health, Faculty of Medicine and Pharmacy, “Dun&abreve;rea de Jos” University, Galați, 800201, Romania; 3“sf. Ioan” Clinical Emergency Children’s Hospital, Galați, 800487, RomaniaCorrespondence: Virginia Marina, Tel +40-770-89-82-74, Email virginia.marina@ugal.roAbstract: Head trauma (HT) in pediatric patients is the number one cause of mortality and morbidity in children. Although computer tomography (CT) imaging provides ample information in assessing acute traumatic brain injuries (TBIs), there are instances when magnetic resonance imaging (MRI) is needed. Due to its high sensitivity in diagnosing small bleeds, MRI offers a well-documented evaluation of primary acute TBIs. Our pictorial essay aims to present some of the latest imaging protocols employed in head trauma and review some practical considerations. Injury mechanisms in accidental HT, lesions’ topography, and hematoma signal variability over time are also discussed. Acute primary intra- and extra-axial lesions and their MRI aspect are showcased using images from patients in our hospital. This pictorial essay has an educational purpose. It is intended to guide young emergency and intensive care unit doctors, neurologists, and neurosurgeons in diagnosing acute primary TBIs on MRI while waiting for the official radiologist’s report. The presentation focuses on the most frequent traumatic lesions encountered in acute pediatric head trauma.Keywords: paediatric head trauma, traumatic brain injury, diffuse axonal injury, haemorrhagic cortical contusions, epidural haematoma

Chih-Yen Hsiao,1 Yi-Chien Lee,2,3 Douglas JH Shyu,4 Che-Ping Su,5 Man-Yi Lin,5 Nai-Yu Guo,6 Cheng-Lun Chiang,1 Yih-Yuan Chen5 1Division of Nephrology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan; 2Department of Internal Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan; 3School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 4Department of Biological Science and Technology, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan; 5Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan; 6Department of Respiratory Care, Chang-Gung University of Science and Technology, Chiayi, TaiwanCorrespondence: Yih-Yuan Chen, Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan, Tel +886-5-271-7795, Email yychen@mail.ncyu.edu.twObjective: The most common extraintestinal pathogen and infection site is uropathogenic Escherichia coli (UPEC), which causes urinary tract infections (UTIs). UPEC is also a common pathogen in bloodstream infections; in severe cases, it can lead to death. Although host and bacterial virulence factors have been demonstrated to be associated with UTI pathogenesis, the role of the related contributing factors in UTI and urinary source bacteremia is not yet fully understood. This study aimed to compare and analyze the factors contributing to urinary bacteremia in patients with UTI.Methods: A total of 171 E. coli strains collected from patients with UTI and urinary source bacteremia at Chiayi Christian Hospital were used. Phylogenetic groups and virulence factors were determined using PCR. Drug resistance patterns were determined using the disk diffusion assay.Results: Previous studies have demonstrated that fimbriae and papGII may be associated with first-step infections and severe UTIs, respectively. As expected, highly virulent E. coli strains (belonging to the phylogenetic B2 and D groups) were dominant in the bacteremic UTI (90%) and UTI (86.27%) groups. However, our results showed that the UTI group had a significantly higher prevalence of sfa/focDE (belonging to the S and FIC fimbriae) than the bacteremic UTI group (29.4% vs 12.5%; p=0.008). In the bacteremic group, we found that sfa/focDE was only detected in highly virulent strains. The bacteremic UTI group had a significantly higher prevalence of papGII (belonging to P fimbriae) than the UTI group (55.8% vs 37.3%; p=0.026). In addition, the P fimbriae gene cluster, including papC, papEF, and papGII, was predominant in highly virulent strains. Notably, our results show that multidrug-resistant (MDR) strains were significantly less virulent than non MDR strains.Conclusion: Taken together, our results provide insights into the contributing factors in patients with UTI and urinary bacteremia.Keywords: Escherichia coli, urinary tract infection, urinary source bacteremia, virulence factors, multidrug resistance

Objetivos: Avaliar o papel de polimorfismos no genoma completo de participantes com doença falciforme (DF) do estudo Recipient Epidemiology and Donor Evaluation Study III no desenvolvimento de Síndrome Torácica Aguda (STA), através do Genome Wide Association Study (GWAS). Material e métodos: Foram realizados questionários e coletas de amostras de 1.930 pacientes com DF em duas visitas diferentes aos Hemocentros de 4 locais do Brasil (SP, RJ, MG, PE), entre os anos de 2014 a 2017. Um microarray customizado foi projetado para cobrir mais de 800 mil polimorfismos usando a plataforma Affymetrix - Axiom Custom Genotyping Platform, sendo denominado como Transfusion Medicine Array. Com esses dados, realizou-se o GWAS, através do pacote R GMMAT, dos softwares PLINK e LocusZoom, realizando as correções para subestrutura populacional e parentesco enigmático, além de estipular um valor de P > 5×10-8 e MAF > 0.05. Resultados: Analisando a coorte completa de pacientes, não obtivemos genes que alteraram o risco da complicação, mas ao dividi-la entre adultos e crianças, um gene se destacou para o grupo infantil, embora não tenha ultrapassado o valor de threshold, sendo ele: ADIPOR2 (valor de p = 1,27 × 10-7), o qual desempenha papéis, na modulação de vias inflamatórias, estresse oxidativo e dissipação de energia, além de ter função na regulação do metabolismo de glicose e lipídeos. Discussão: No Brasil, entre 2017 a 2021, houveram cerca de 2.268 óbitos registrados nos estabelecimentos do SUS em consequência da DF. Atualmente a STA é a segunda maior causa de morte em pacientes com essa doença. O papel da modulação inflamatória no desenvolvimento desta complicação parece ser de extrema importância. A adiponectina, ligante de ADIPOR2, apresenta papel anti-inflamatório em condições pulmonares e sua expressão parece modular-se ao metabolismo energético. É possível que a via esteja relacionada ao aparecimento da complicação em pacientes com DF. Conclusão: Os resultados sugerem uma associação entre o polimorfismo de ADIPOR2 no desenvolvimento de STA. Os achados bibliográficos sobre ADIPOR2 foram condizentes com o que foi encontrado neste trabalho, visto que mostram um papel desse gene no desenvolvimento de doenças pulmonares, como asma, DPOC e doenças infecciosas de vias respiratórias.

Introdução/Objetivos: A doença falciforme é caracterizada pela presença do alelo βsque, quando em homozigose, identifica a anemia falciforme (HbSS). A fisiopatologia da doença induz à ativação e expressão de uma série de moléculas e células na circulação, responsáveis pela instauração de um processo inflamatório crônico. O fenótipo Duffy nulo, resultado de uma mutação pontual no box do promotor eritroide GATA-1, pode interferir nesse processo inflamatório, uma vez que leva ao silenciamento da expressão do antígeno Fyb na membrana das hemácias que, quando presente, atua como um receptor para quimiocinas pró-inflamatórias. Assim, o presente trabalho buscou identificar a influência da mutação em GATA-1 no processo inflamatório de indivíduos falciformes. Material e métodos: O genótipo Duffy de cada indivíduo foi identificado a partir da genotipagem dos alelos FY*01, FY*02 e FY*02N.01 em amostras de DNA de indivíduos falciformes e de doadores de sangue saudáveis. Também, foram coletadas amostras de soro de todos os indivíduos para realização da dosagem dos marcadores de inflamação e hemólise: proteína C reativa (PCR), interleucina-8 (IL-8), interleucina-1β (IL-1β) e lactato desidrogenase (LDH). Ainda, dados referentes ao uso de hidroxiureia pelos indivíduos falciformes foram coletados acessando o prontuário dos pacientes. Foram incluídos no estudo indivíduos HbSS estáveis e não transfundidos em pelo menos um mês anterior à coleta das amostras. Todos os indivíduos incluídos apresentaram idade igual ou maior a 18 anos. Resultados: Foram coletadas amostras de 37 indivíduos HbSS e 37 doadores de sangue saudáveis, sendo identificada diferença estatística significativa nos níveis de IL-8 (p < 0,001), PCR (p < 0,001) e LDH (p < 0,001) entre os grupos, onde os indivíduos falciformes apresentaram os maiores níveis séricos dos três marcadores. O uso de hidroxiureia pelos indivíduos falciformes não demonstrou interferência nos níveis das interleucinas analisadas, sendo identificada diferença apenas nos níveis de PCR e LDH com o uso do medicamento. Em relação aos genótipos, foi verificada diferença estatística significativa apenas nos níveis de IL-8 (p = 0,003), com os maiores níveis encontrados nas amostras de indivíduos mutados em homozigose (FY*02N.01/FY*02N.01). Discussão: Os resultados obtidos na comparação dos indivíduos falciformes com os doadores saudáveis já eram esperados devido a inflamação crônica presente no primeiro grupo. Apesar da influência da hidroxiureia nos níveis de PCR e LDH, os níveis de ambos os marcadores permaneceram significativamente maiores em comparação com os marcadores nos doadores saudáveis, não interferindo nas análises realizadas no estudo. Não há consenso na literatura acerca da influência do antígeno Duffy nos níveis de IL-8 em indivíduos falciformes, onde o presente trabalho contribui demonstrando que a mutação em GATA-1 em homozigose pode influenciar nos níveis de IL-8 nesses indivíduos, sugerindo um maior risco de vaso-oclusão, uma vez que a IL-8 tem importante efeito na formação de pequenos trombos e a própria fisiopatologia da doença leva a uma predisposição à ocorrência de crises vaso-oclusivas. Conclusão: A partir dos resultados, conclui-se que a presença do alelo mutado em homozigose tem associação com os níveis de IL-8, contribuindo para a manutenção do processo inflamatório e maior risco vaso-oclusivo nesses indivíduos.

Introdução/Objetivos: As razões derivadas do hemograma, como a razão neutrófilo-linfócito (NLR), razão plaqueta-linfócito (PLR), razão neutrófilo-plaqueta (NPR) e índice de imuno-inflamação sistêmica (SII), têm sido cada vez mais pesquisadas e utilizadas como preditores de severidade de diversas doenças e indicadores de inflamação sistêmica. A doença falciforme é caracterizada por uma inflamação crônica que pode ser influenciada por fatores imunológicos e/ou genéticos, os quais são capazes de modular a resposta inflamatória e, consequentemente, alterar o quadro clínico e a severidade da doença. Nesse sentido, a mutação em GATA-1 se apresenta como um possível interferente que leva a uma resposta inflamatória exacerbada, uma vez que o receptor que auxilia na modulação das citocinas não está presente na circulação. Dessa maneira, o objetivo do presente trabalho foi identificar as razões derivadas do hemograma em indivíduos falciformes e verificar a influência da mutação em GATA-1 nesses parâmetros. Material e métodos: As razões derivadas do hemograma analisadas foram a NLR, PLR, NPR e SII. Os dados utilizados para os cálculos das razões foram coletados a partir do hemograma de indivíduos falciformes (HbSS) estáveis e de controles aparentemente saudáveis, ou seja, indivíduos que não apresentaram alteração dos parâmetros hematológicos, detectados pelos resultados do hemograma. A pesquisa pela mutação em GATA-1 foi realizada utilizando a técnica de genotipagem (PCR-SSP) a partir do DNA extraído das amostras de sangue total dos indivíduos falciformes. Todos os indivíduos incluídos no estudo apresentaram idade maior ou igual a 18 anos. A análise estatística foi realizada utilizando-se os testes U de Mann-Whitney ou T student. Resultados: Foram analisados os dados de 37 indivíduos falciformes e 37 controles. Foi verificado aumento significativo nos valores de PLR (136 ± 53; 109 ± 33, p = 0,012) e SII (631 ± 417; 342 ± 129, p < 0,001) nos indivíduos falciformes com relação aos controles. Em relação à presença da mutação em GATA-1, foi verificado aumento significativo (p = 0,023) apenas nos valores medianos de PLR nos indivíduos falciformes mutados (176; 116 - 196) com relação aos não mutados (103; 79 - 163). Discussão: Os valores de SII maiores nos indivíduos falciformes em comparação aos controles indica uma relação descompensada entre inflamação e resposta imune nos indivíduos HbSS, resultado que reforça a inflamação crônica presente nesses indivíduos. A PLR é um marcador que revela mudanças nas contagens de plaquetas e linfócitos devido a estados inflamatórios e pró-trombóticos. A diferença observada nos valores de PLR entre os indivíduos falciformes e os controles já era esperada, uma vez que esse parâmetro está associado à trombocitose, fator diretamente relacionado à fisiopatologia da doença falciforme e que leva à vaso-oclusão. Ainda, os maiores valores de PLR encontrado nos indivíduos falciformes GATA-1 mutados em comparação aos indivíduos não mutados, sugere o aumento do estado inflamatório e pró-trombótico no primeiro grupo. Conclusão: Os resultados obtidos reforçam a presença de um estado inflamatório crônico no indivíduo HbSS e indicam uma possível interferência da mutação em GATA-1 na intensidade inflamatória e no estado pró-trombótico da doença falciforme.

Introdução: A Doença Relacionada a Imunoglobulina G4 (DR-IgG4) é um distúrbio imunomediado fibroinflamatório raro que pode afetar vários órgãos. A incidência estimada de 0,78-1,39 por 100.000 pessoas/ano. A fibrose retroperitoneal é comumente encontrada na DR-IgG4. Atinge homens entre a 6ª e 7ª décadas de vida. Os critérios diagnósticos ainda não estão bem estabelecidos, pois a clínica é variada. O curso da doença tem sido alterado com uso de corticoides e imunossupressores. Objetivo: Relatar o caso de um paciente com massa retroperitoneal com suspeita de linfoma de alto grau, cujo diagnóstico foi de fibrose associada à DR-IgG4. Relato: Paciente masculino, 40 anos, de Andorinha-BA, procurou atendimento em unidade hematológica particular em outubro de 2023, com queixa de mal-estar, náuseas, redução de forças em membros inferiores e perda ponderal de 9 kg em 2 meses. No exame físico apresentava-se descorado (+/4+), com massa palpável em região periumbilical de cerca de 5 cm, indolor à palpação. Exames laboratoriais: hemoglobina 10,8 g/dL; leucócitos 4580/mm3; plaquetas 256 mil/mm3; creatinina 4,4 mg/dL; ureia 210 mg/dL; cálcio 9,1 mg/dL. Ultrassonografia evidenciou hidronefrose bilateral. Encaminhado ao nefrologista, que solicitou tomografia computadorizada de urgência. Foi evidenciada massa em região retroperitoneal em torno da aorta e das artérias ilíacas, englobando estruturas vasculares e segmentos médios de ambos ureteres, com redução do calibre da veia renal esquerda e sinais de nefropatia crônica do rim esquerdo, com possibilidade de fibrose retroperitoneal. O urologista indicou cateter duplo J e linfadenectomia cervical esquerda. O anatomopatológico foi negativo. Foi encaminhado ao hematologista, que solicitou uma biópsia aberta abdominal revelando presença de tecido fibroso associado à infiltrado inflamatório mononuclear crônico e ausência de malignidade. Referenciado à reumatologia com suspeita de DR-IgG4, que durante investigação detectou níveis aumentados de IgG4 (214 mg/dL). Iniciou corticoterapia oral e Azatioprina, com regressão total dos sintomas em 2 semanas. Paciente manteve acompanhamento com reumatologista, nefrologista e urologista, e após 4 meses de tratamento, houve normalização da função renal e redução significativa da massa abdominal. Segue em programação para retirada de duplo J. Discussão: A DR-IgG4 pode afetar diversos órgãos. Há uma resposta imunológica anormal, com infiltração de células plasmáticas produtoras de IgG4 e subsequente fibrose podendo causar obstrução ureteral e insuficiência renal. Os pacientes são assintomáticos, mas em uma minoria há linfadenopatia acompanhada de sintomas sistêmicos, como febre e perda de peso, sendo importante considerar o linfoma e a leucemia como diagnósticos diferenciais. A identificação precoce é crucial para prevenir danos irreversíveis aos órgãos. A elevação sérica de IgG4 é um marcador importante para o diagnóstico, juntamente com o histopatológico. O tratamento padrão envolve o uso de corticoides, que são eficazes na maioria dos casos. O uso de Azatioprina e Rituximabe é uma alternativa farmacológica para terapias de manutenção com intuito de evitar recidivas e controlar a atividade da doença a longo prazo. Conclusão: O diagnóstico é desafiador pela possibilidade de simular outras doenças linfoproliferativas e a busca pelo diagnóstico é crucial para o tratamento e prognóstico do paciente.

Introduction: Idiopathic multicentric Castleman's disease (iMCD) is an ultra rare lymphoproliferative disorder difficult to diagnose due to its rarity (prevalence of 6.9-9.7 cases per million in the United States) and the lack of awareness among physicians. Median time between symptoms onset and the diagnosis of iMCD in Brazil is estimated to be 18 months. We propose that an artificial intelligence (AI)-based algorithm working on electronic health records may help to identify patients suspected of Castleman disease that were missed during medical evaluation. Methods: Firstly, symptoms listed in the CDCN iMCD criteria [Fajgenbaum DC, et al. Blood. 2017;129(12):1646-57] were defined by medical terms. Medical definition contained ICD - 10 codes, lab test results and phrases that may be found in the medical texts (descriptions of imaging tests, interviews, epicrisis). SPACY models with in house developed regular expressions (regex) were used to identify phrases (entities) assigned to symptoms in the unstructured medical texts. Entity context defined as negation, family relation, historical or hypothetical event was determined by the BERTH model that went through additional training on the Saventic database. Patients were ranked based on the symptoms they possessed. Patients were ranked only when lymphadenopathy was identified and patients already diagnosed with iMCD (four cases) were excluded. Physicians with expertise in iMCD led the review of patients’ charts with the highest score. Results: 594 953 patients'charts from a tertiary Brazilian hospital were screened by the algorithm and iMCD clinical and/or laboratory features were identified in 102 patients, which had higher probability of having iMCD. Of those, 12 had mimicker conditions with overlapping iMCD features and three others required further assessment. Conclusion: This AI driven tool was able to identify patients who have iMCD features. Screening with this tool found at least three candidates for additional evaluation. In the future, algorithms like the one we present may facilitate screening for iMCD. Conflicts of interest: AAGSB, DL: Saventic Health (honoraria). MK, WA, GB, KL, MJD, MD: Saventic Health (current employment).

Introdução: Osteopetrose é um grupo de displasias ósseas raras e hereditárias, caracterizadas pelo aumento da massa óssea. Há diferentes subtipos e pode se manifestar de forma leve a fatal. A osteopetrose maligna da infância possui alta morbimortalidade, com formas graves surgindo logo após o nascimento. Objetivos: Descrever características clínicas, radiológicas e laboratoriais de uma paciente com Osteopetrose Maligna e realizar uma revisão bibliográfica não sistemática com base em artigos publicados em banco de dados de periódicos nacionais e internacionais nos últimos dez anos. Relato do caso: Lactente de 1 ano e 10 meses, previamente hígida, foi diagnosticada com anemia grave e plaquetopenia leve em exames pré-operatórios para correção de craniossinostose, sendo encaminhada para investigação pela Hematologia Pediátrica. Além da craniossinostose, apresentava esplenomegalia e sangue periférico leucoeritroblástico. O aspirado e a biópsia de medula óssea foram tecnicamente difíceis de serem realizados e imediatamente levantaram a suspeita de osteopetrose, a imunofenotipagem afastou leucemias. O inventário radiológico revelou aumento difuso da densidade óssea, com imagens características de osteopetrose, como vértebras em sanduíche. A tomografia de crânio mostrou hipertensão intracraniana compensada, com sinais de compressão de canal auditivo, órbita e nervo óptico; ainda sem manifestações clínicas, exceto pelo papiledema. Além de anemia, leucocitose e plaquetopenia, hipocalcemia e hiperfosfatemia também foram encontradas. A paciente foi encaminhada para avaliação pelo centro transplantador em cinco meses após o diagnóstico, para ser submetida ao transplante de células tronco hematopoiéticas (TCTH) alogênico não aparentado. Discussão: Osteopetrose é um grupo raro de doenças hereditárias caracterizado pelo aumento anormal da densidade óssea. Na maior parte dos casos, o crescimento ósseo excessivo ocorre devido à redução da reabsorção osteoclástica e compromete funções hematológicas e neurológicas. Achados como anemia, hepatoesplenomegalia, cegueira, surdez e paralisias por compressões nervosas podem ocorrer. As manifestações podem ser leves a graves, relacionadas a mutações genéticas. Os tipos principais incluem a forma infantil autossômica recessiva também chamada de maligna da infância, a intermediária e as autossômicas dominantes tipo I e II. Cada subtipo apresenta padrões radiológicos distintos, facilitando o diagnóstico. A radiografia também é capaz de monitorar progressão de doença e resposta ao tratamento. Mutações em genes como TCIRG1, OSTM1 e CLCN7 são associadas à osteopetrose. O exame genético é o padrão ouro para determinar mutação, subtipo e prognóstico, porém há difícil acessibilidade no sistema público de saúde. O TCTH é eficaz nas formas graves, mas contraindicado em casos neurodegenerativos ou algumas mutações específicas. A abordagem multidisciplinar é essencial para o tratamento. Diagnóstico precoce e tratamento rápido também permitem que danos secundários como perda visual e auditiva, que não são revertidos com TCTH, sejam evitados, o que também é ainda distante da realidade atual por desconhecimento da doença. É importante que haja ampla divulgação do tema entre os profissionais de saúde. Conclusão: Por ser uma condição rara e grave, é necessária a suspeição clínica e diagnóstico precoce para que a terapêutica rápida e o acompanhamento multidisciplinar sejam mais efetivos.

Introdução: Alguns pacientes apresentam reações alérgicas às proteínas do plasma presentes em pequeno volume no concentrado de hemácias, sendo necessário um procedimento para remoção do mesmo. É necessário que o concentrado de hemácias seja submetido ao procedimento de “lavagem”com o uso de salina 0.9% a 4ºC e através de centrifugação, o plasma é removido juntamente com restos celulares e alguns leucócitos. O manual (AABB) preconiza o uso do volume de salina entre 1.000 e 2.000 ml garantindo que a qualidade final do hemocomponente esteja conforme com a legislação vigente. Os pacientes com indicação de uso de hemácias”lavadas”são: paciente com deficiência de IgA, História de reação alérgica grave ou reação anafilática em transfusão anterior, História de reação alérgica moderada ou leve mesmo com o uso pré-transfusional preventivo de antialérgicos. Materiais e métodos: Foi realizado um estudo retrospectivo a partir de janeiro de 2021 até dezembro de 2023, com o objetivo de avaliar os parâmetros de qualidade dos concentrados de hemácias lavados no Banco de sangue Vita Hemoterapia da Bahia. Resultados: Foram avaliadas 13 unidades de concentrado de hemácias (CH) com aditivo SAGM, antes e após o procedimento de lavagem. O CH lavado é obtido após três lavagens sucessivas das hemácias com solução salina 0,9%, a fim de remover a maior quantidade possível de plasma. O procedimento de lavagem é realizado em CH com até 10 dias de coleta e com prova de compatibilidade negativa. Constitui em centrifugar o CH a 2.500 rpm por 7 minutos ou 4000 rpm por 10 minutos, dependendo da centrifuga utilizada, a temperatura de 4ºC. O soro fisiológico 0,9% é colocado previamente na geladeira, temperatura entre 2ºe 6 ºC, para atingir a mesma temperatura do CH. A centrifuga é ligada 30 minutos antes e programada para temperatura de 4°C. O sobrenadante é desprezado, e acrescentado 250 ml de salina, através de conexão estéril (Genesis BPS) por três vezes. Após descartar o sobrenadante da terceira lavagem, adicionar aproximadamente 100 ml de solução fisiológica 0,9% à bolsa de concentrado de hemácias para manter o hematócrito conforme legislação vigente. Amostras foram coletadas por conexão estéril, antes e após o procedimento para realização do controle de qualidade. Os valores médios obtidos do CH pós lavagem foram: recuperação celular de 96 %, hematócrito de 51 %, grau de hemólise 0,4 % e proteínas totais igual a 0,4 g/unidade. Todas apresentaram resultados negativos no teste microbiológico. As transfusões foram realizadas sem intercorrências. Conclusão: O processo de lavagem de CH mostrou-se eficiente. Foi usando um volume aproximado de 1000 ml de salina 0,9%, sem interferir na qualidade final do hemocomponente conforme os parâmetros estabelecidos na legislação vigente, proporcionando uma transfusão segura e sem prejuízo para o paciente.

Objetivos: Analisar as solicitações, distribuição e descarte de Concentrado de Hemácia (CH) através do estoque estratégico do Hemocentro do HCFMB, para atender a demanda das Agências Transfusionais da região de abrangência. Material e métodos: Os dados foram obtidos nos registros do Laboratório de Componentes Lábeis do Hemocentro do HCFMB no período de 2021 a 2023. Foram analisadas as solicitações para estoque das Agências transfusionais identificadas como X, Y, Z, W, A, B, C e o índice de descarte de CH dos anos 2022 e 2023. Resultados: Somando os três anos, o Hemocentro distribuiu 14.102 bolsas de CH, sendo em 2021 enviados 4.830, em 2022 enviados 4.397 e em 2023 enviados 4.875. Em relação às Agências, somando a quantidade de CH solicitados e enviados, dos últimos três anos, 21,43% do que foi pedido não foi enviado, sendo 24,08% em 2021, 23,87% em 2022 e 16,36% em 2023. Entretanto, mesmo não sendo enviados em suas totalidades, em 2022 a média de bolsas enviadas que foram descartadas foi de 15% e em 2023 de 14,28%. Em 2022, a cidade X registrou uma média de 22,75% não enviadas e 6,81% de descartadas. Na cidade Y, as médias foram de 29,39% e 9,80%, respectivamente. Já a cidade Z apresentou uma média de 9,24% de não enviadas e 11,20% de descartadas. A cidade W teve uma média de 18,74% de não enviadas e 8,28% de descartadas, enquanto a cidade B registrou 29,38% de não enviadas e 36,32% de descartadas. A cidade A teve uma média de 26,27% de não enviadas e 21,30% de descartadas, e a cidade C apresentou 16,98% de não enviadas e 14,67% de descartadas. Já em 2023 a cidade X reduziu suas taxas para 13,25% de não enviadas e teve um aumento na porcentagem de descartadas, sendo 9,55%. A cidade Y também teve uma queda, com 20,3% de não enviadas e o mesmo padrão de aumento de descartadas, sendo 11,75%. A cidade Z obteve melhorias consideráveis, com apenas 5,41% de não enviadas e 9,97% de descartadas. Na cidade W, as taxas foram de 17,1% de não enviadas e 8,48% de descartadas. A cidade B, demonstrou uma queda na quantidade de não enviadas e descartadas, sendo respectivamente 20,29% e 31,81%. A cidade A apresentou 20,87% de não enviadas e 15,43% de descartadas. Por fim, a cidade C teve 11,11% de não enviadas e 13,01% de descartadas. Discussão: Nota-se que houve em vários pedidos a solicitação das cidades sem o uso do estoque estratégico, e verificamos a distribuição sem seguir o estoque pré-estabelecido. Essa análise justifica algumas situações de descarte que poderiam ser evitadas, se houvesse o emprego dos valores estabelecidos pelo cálculo de estoque estratégico. Conclusão: Identificamos fragilidades no manejo do estoque estratégico, problema enfrentado globalmente devido à natureza perecível do sangue e a sazonalidade das demandas. Sugerimos o uso habitual do estoque estratégico na distribuição mediante as solicitações de CH evitando o descarte de sangue. Além da implementação de um manejo eficiente na utilização de sangue, com a adoção dos protocolos de PBM (Patient Blood Management).

Introdução: Nos EEUU, estima-se transfusões em 11 milhões de unidades de concentradode hemácias, 2,5 milhões de plaquetas, 2,2 milhões de bolsas de plasma e 1,2 milhões decrioprecipitados ao ano. Embora não dispondo de dados no Brasil, pode-se inferir que aordem de grandeza seja semelhante. Dentro deste contexto, a doação de sangue é atohumano, crucial para a prática médica e consequente busca de recuperação de pacientesem suas mais diversas comorbidades. O ato de doação não pode ser recompensadofinanceiramente em nosso país, dependendo apenas de empatia e boa vontade , por nãohaver substituto para sangue humano só podendo conseguí-lo através da doaçãovoluntária. Em nosso Hemocentro estima-se perda mensal de cerca de 25% de doadoresdevido a aferição de hemoglobina capilar estar acima de 18 g/dL, caracterizandopoliglobulia. Este achado demanda avaliação em dois braços principais: a) poliglobuliaclonal, causada por mutação genética estabelecida, caracterizando hemopatia primária(Policitemia Vera); b) secundária, relacionada a condição comórbida (ex: Tabagismo, DPOC, SAHOS, Cistos renais e hepáticos, leiomiomas, etc.) ou dependente do grau de hidratação(suficiente vs insuficiente), quando o doador está desidratado. Isto leva a reduzido volumeplasmático, que culmina em aparente aumento dos valores numéricos de hematócrito ehemoglobina, consideradas as unidades em volume plasmático de plasma (Ht%) ehemácias (/mm 3 ) em ambas as aferições. Este trabalho buscou avaliar este segundo grupode pacientes tomados como poliglobúlicos, de forma a propor intervenção simples eacessível, como hidratação oral para reversão do achado eritrométrico que dispensavapotenciais doadores e consequente perda da doação. Objetivo: Relatar recuperação dedoadores anteriormente rejeitados e aprovados após hidratação oral, no Hemocentro HC-FMB-UNESP. Método: Através de duas aferições iniciais de Hb capilar maior que 18 g/dL,instituíu-se o seguinte protocolo: 3 a 4 copos de água aguardando-se 30 minutos deintervalo, seguido de nova aferição de Hb capilar. Se o valor de Hb se mantivesse apóshidratação, ao paciente seria negada a realização da doação; porém se o valor diminuisseabaixo de 18 g/dL, o doador seria liberado para doação. Foram acompanhadas as doaçõesdo período de julho de 2023 a maio de 2024. Resultados: Nos meses de Julho, Agosto eSetembro/2023 obteve-se recuperação de cerca de 40% dos doadores após a hidrataçãooral. De Outubro a Dezembro/2023 a recuperação foi de cerca de 50% dos doadores; emJaneiro/2024 foi de 70% dos doadores, seguido de 40% em Fevereiro, e de 70% em Marçodo mesmo ano. Em Abril registrou-se 50% de doadores aptos à doação após hidratação,fechando o período em maio com 35% de recaptação. No período analisado, a média derecuperação foi de 49,5%, resultando em um ganho de n = 103 bolsas de sangue, que nãoseriam coletadas, caso não houvesse sido implementada esta intervenção. Conclusão: Anecessidade de se criar estratégias que diminuam a perda de doações de bolsas de sangue– as quais constituem em terapia utilizada para procedimentos decisivos e que mudam ocurso evolutivo de muitos pacientes, se faz necessária, considerando-se a frequência comque se prescreve transfusões de sangue. Desta forma, o presente projeto buscou criarestratégia simples, barata e efetiva para recuperar potenciais doadores no Hemocentro deBotucatu e que se mostrou efetiva e eficaz.

Objetivo: Avaliar os fatores pré-operatórios e intraoperatórios associados à utilização de concentrado de hemácias em cirurgias cardíacas eletivas realizadas no Hospital das Clínicas da Faculdade de Medicina de Botucatu. Material e métodos: Um estudo retrospectivo observacional com coleta de dados foi realizado, entre 2018 e 2021, o qual se obteve 741 indivíduos. Os dados alcançados foram avaliados por meio de análise descritiva, teste Qui-quadrado e Regressão Logística (stepwase), considerando o nível de significância de 5%. Resultados: Parâmetros pré-operatórios, como feminino biológico feminino (OR 9,074; IC95% 5,218; p < 0,0001), seguido do hematócrito baixo (OR 7,498; IC95% 4,362; p = 0,0034), presença de diabete mellitus (DM) (OR 1,779; IC95% 1,052; p = 0,0318) e intraoperatório, como tempo de circulação extracorpórea acima de 90 minutos (OR 1,68; IC95% 1,013; p = 0,0442) mostraram-se de riscos para o sangramento excessivo e/ou indispensabilidade do uso de concentrados de hemácias durante a cirurgia. Discussão: Sabe-se que as mulheres, em sua maioria, apresentam maior prevalência de anemia, principalmente associados a fatores como menstruação, gravidez e lactação. Sob a mesma perspectiva, a anemia pré-operatória possui associação a comorbidades, idade avançada e o sexo feminino, sendo todos eles destacados pela literatura como fatores de risco para resultados adversos após cirúrgicas cardíacas. Em relação ao tempo de circulação extracorpórea (CEC) acima de 90 minutos, sabe-se que a técnica de CEC, é potencialmente categorizada como uma das principais causas de sangramento em todo o período perioperatório, tendo em vista os distúrbios de coagulação e ativação de fibrinólise, fatores esses que são reforçados com a presença do enorme tempo de uso e, o último, considerado um dos principais fatores de sangramento em cirurgias cardíacas com uso de CEC. Somado a esses fatores, ressalta-se que um paciente que apresenta hematócrito abaixo de 40% e necessidade do uso de CEC, tem maior chance de usar sangue em cirurgias de revascularização do miocárdio, concernindo ao uso de hemocomponentes encontrado no presente trabalho. Embora a literatura apresente grandes estudos sobre DM, ainda não é possível comprovar a relação entre a presença dessa comorbidade e a necessidade transfusional na literatura, levantando-se três possíveis fatores envolvidos nessa relação para os resultados encontrados no presente estudo: complicações vasculares devido a resistência à insulina, a prevalente presença de anemia em pacientes com DM e, por conseguinte, necessidade transfusional, e o fato do sexo feminino estar mais associado a complicações vasculares na DM, todos achados correlacionados entre si e com os resultados do presente trabalho. Conclusão: Os fatores de risco pré-operatórios, como sexo biológico feminino, hematócrito diminuído e presença de diabetes mellitus, e intraoperatórios, como o uso de circulação extracorpórea acima de 90 minutos, demonstraram-se estar associados à utilização de concentrados de hemácias em cirurgias cardíacas eletivas realizadas entre 2018 e 2021.