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Background: Periprosthetic osteolysis is a prevalent complication following total ankle arthroplasty (TAA), implicating various cytokines in osteoclastogenesis as pivotal in this process. This study aimed to evaluate the relationship between osteolysis and the concentrations of osteoclastogenesis-related cytokines in synovial fluid and investigate its clinical value following TAA. Methods: Synovial fluid samples from 23 ankles that underwent revision surgery for osteolysis following TAA were analyzed as the osteolysis group. As a control group, we included synovial fluid samples obtained from 23 ankles during primary TAA for osteoarthritis. The receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in these samples was quantified using sandwich enzyme-linked immunosorbent assay techniques, and a bead-based multiplex immunoassay facilitated the detection of specific osteoclastogenesis-related cytokines. Results: RANKL levels averaged 487.9 pg/mL in 14 of 23 patients in the osteolysis group, with no detection in the control group's synovial fluid. Conversely, a significant reduction in OPG levels was observed in the osteolysis group (p = 0.002), resulting in a markedly higher mean RANKL/OPG ratio (0.23) relative to controls (p = 0.020). Moreover, the osteolysis group had increased concentrations of various osteoclastogenesis-related cytokines (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, IL-8, IP-10, and monocyte chemotactic protein-1) in the synovial fluid relative to the control group. Conclusions: Our results demonstrated that periprosthetic osteolysis was associated with osteoclastogenesis activation through an elevated RANKL/OPG ratio following TAA. We assume that RANKL and other osteoclastogenesis-related cytokines in the synovial fluid have clinical value as a potential marker for the development and progression of osteolysis following TAA.
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Artroplastia de Substituição do Tornozelo , Biomarcadores , Osteólise , Osteoprotegerina , Ligante RANK , Líquido Sinovial , Humanos , Líquido Sinovial/metabolismo , Líquido Sinovial/química , Osteólise/metabolismo , Osteólise/etiologia , Masculino , Feminino , Ligante RANK/metabolismo , Idoso , Pessoa de Meia-Idade , Artroplastia de Substituição do Tornozelo/efeitos adversos , Osteoprotegerina/metabolismo , Osteoprotegerina/análise , Biomarcadores/metabolismo , Biomarcadores/análise , Idoso de 80 Anos ou mais , Citocinas/metabolismo , Citocinas/análise , ReoperaçãoRESUMO
PURPOSE: To observe the rate of progressive retinal nerve fiber layer (RNFL) thinning in the unaffected eyes of patients with unilateral normal-tension glaucoma (NTG), in comparison with that of healthy subjects, and to identify the factors associated with progressive RNFL thinning. DESIGN: Retrospective, longitudinal, observational study. PARTICIPANTS: Ninety-five patients with unilateral NTG and 61 healthy controls. METHODS: This study included unilateral NTG and healthy control subjects who were followed up for longer than 4 years and in whom at least 5 reliable retinal nerve fiber layer thickness (RNFLT) measurements were performed using OCT. Factors associated with the rate of thinning of the unaffected eyes of unilateral patients with NTG were identified using regression analysis. MAIN OUTCOME MEASURES: The rate of progressive RNFL thinning and the associated factors. RESULTS: Retinal nerve fiber layer thickness decreased significantly in both the unaffected eyes of unilateral patients with NTG and the healthy eyes (both P < 0.001). The RNFL thinning was significantly faster in the unaffected eyes of unilateral patients with NTG than in the healthy eyes (P < 0.001), specifically in the temporal-inferior (TI) sector (P = 0.003). Factors associated with faster RNFL thinning in the unaffected eyes of unilateral patients with NTG were thicker baseline RNFL of the unaffected eyes (P = 0.002) and a worse visual field (VF) mean deviation (MD) in the NTG eyes (P = 0.040). In the healthy controls, the rate of RNFL thinning in the contralateral eyes was the only factor associated with faster thinning (P = 0.007). CONCLUSIONS: The unaffected eyes of unilateral patients with NTG showed faster RNFL thinning than healthy control eyes, more obviously in the TI sector, and were likely to progress faster when they had a thicker baseline RNFL, and when the NTG eyes had a worse VF MD. In unilateral patients with NTG, initiation of prophylactic treatment could be considered for the unaffected eyes when they are accompanied by a risk of developing glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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L-ascorbic acid (AA), a potent antioxidant, is commonly used topically in the pharmaceutical and cosmetic fields. However, the incorporation of AA into topical formulations is difficult because of its highly unstable nature and relatively poor skin permeability. In this study, we propose an alternative strategy for improving the solubility and topical delivery of AA through its conversion to a therapeutic deep eutectic system (THEDES). AA and betaine (Bet)-based THEDESs were prepared at certain molar ratios and characterized using polarized optical microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Solubility tests showed that AA in the form of THEDES was readily soluble in various polyols (glycerin, 1,3-butylene glycol, dipropylene glycol, and 1,3-propanediol) at a high concentration (approximately 40%). Furthermore, compared to AA alone or the physical mixture of AA and Bet, AA-based THEDES significantly enhanced AA delivery through porcine skin. In an in vivo human study, THEDES-containing serum reduced the markers of aging and induced an even skin tone. These findings indicate the utility of AA and Bet-based THEDES as novel transdermal delivery systems for AA. Furthermore, our approach also showed good extension to developing gluconolactone, a well-known natural antioxidant, and Bet-based THEDES, showing potential application in transdermal delivery systems.
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Purpose: Anti-obesity medications (AOMs), along with lifestyle interventions, are effective means of inducing and maintaining weight loss in patients with obesity. Although the efficacy of AOMs has been reported, there have been no direct comparisons of these drugs. Therefore, in the present study, we aimed to compare the efficacy of all the AOMs available in Korea in a real-world setting. Patients and Methods: The body weight and composition of 205 adults treated with phentermine, phentermine/topiramate, liraglutide, naltrexone/bupropion, lorcaserin, or orlistat for at least 6 months were analyzed at 2 month intervals. The prevalence of the achievement of a ≥5% weight loss and the changes in body composition were compared between participants using each AOM at each visit. Results: A total of 132 (64.4%) participants achieved ≥5% weight loss within 6 months (prevalence of ≥5% weight loss after 6 months: phentermine, 87.2%; phentermine/topiramate, 67.7%; liraglutide, 58.1%; naltrexone/bupropion, 35.3%; lorcaserin, 75%; orlistat, 50%). At each visit, after adjustment for age, sex, and baseline body weight, phentermine use was associated with a significantly higher prevalence of ≥5% weight loss than the use of the other AOMs, except for liraglutide. There were significant differences in the body weight, body mass index and body fat mass among the AOM groups by visit (P for interaction <0.05), but not in their waist circumference, skeletal muscle mass, percentage body fat, or visceral fat area. Conclusion: All the AOMs were effective at inducing and maintaining weight loss, in the absence of significant changes in muscle mass, over a 6 month period, and the short-term use of phentermine and the long-term use of phentermine/topiramate or liraglutide would be practical choices for the treatment of obesity. However, further, large-scale studies are necessary to confirm these findings.
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Fármacos Antiobesidade , Liraglutida , Adulto , Humanos , Orlistate/uso terapêutico , Topiramato/uso terapêutico , Liraglutida/uso terapêutico , Naltrexona/uso terapêutico , Bupropiona/uso terapêutico , Frutose , Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Peso Corporal , Fentermina/efeitos adversos , Redução de PesoRESUMO
BACKGROUND: Limited information is available concerning the epidemiology of stroke and acute myocardial infarction (AMI) in the Republic of Korea. This study aimed to develop a national surveillance system to monitor the incidence of stroke and AMI using national claims data. METHODS: We developed and validated identification algorithms for stroke and AMI using claims data. This validation involved a 2-stage stratified sampling method with a review of medical records for sampled cases. The weighted positive predictive value (PPV) and negative predictive value (NPV) were calculated based on the sampling structure and the corresponding sampling rates. Incident cases and the incidence rates of stroke and AMI in the Republic of Korea were estimated by applying the algorithms and weighted PPV and NPV to the 2018 National Health Insurance Service claims data. RESULTS: In total, 2,200 cases (1,086 stroke cases and 1,114 AMI cases) were sampled from the 2018 claims database. The sensitivity and specificity of the algorithms were 94.3% and 88.6% for stroke and 97.9% and 90.1% for AMI, respectively. The estimated number of cases, including recurrent events, was 150,837 for stroke and 40,529 for AMI in 2018. The age- and sex-standardized incidence rate for stroke and AMI was 180.2 and 46.1 cases per 100,000 person-years, respectively, in 2018. CONCLUSION: This study demonstrates the feasibility of developing a national surveillance system based on claims data and identification algorithms for stroke and AMI to monitor their incidence rates.
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BACKGROUND: This study investigated the association between atherosclerosis and systemic inflammation markers, specifically the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), in healthy middle-aged adults. METHODS: A retrospective cross-sectional study was conducted on a total of 1264 Korean adults aged 40-65. We assessed these inflammatory markers and carotid metrics, such as carotid intima-media thickness (cIMT), plaque number (PN), plaque stenosis score (PSS), and plaque score (PS), using linear regression, logistic regression, and receiver operating characteristic analysis. RESULTS: In males, the ESR and CRP were significantly correlated with the PN (p < 0.001 and p = 0.048, respectively). The ESR was correlated with the PN in females (p = 0.004). The NLR and PLR both correlated with the PS in males (p < 0.001 and p = 0.015, respectively) and females (p = 0.015 and p = 0.023, respectively). The odds ratio for the NLR as a risk factor for increased cIMT was 1.15 (95% confidence interval [CI], 1.03-2.15) for males and 1.05 (95% CI, 1.01-1.29) for females. The AUC for the NLR and PLR as a predictor for the PS showed significance in both men and women. CONCLUSIONS: Inflammatory markers, particularly the NLR and PLR, demonstrate a correlation with carotid atherosclerosis. Both the NLR and PLR hold potential as valuable surrogate markers for carotid atherosclerosis. To further substantiate their predictive efficacy, further prospective studies are needed.
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BACKGROUND: Measurement of sodium intake in hospitalized patients is critical for their care. In this study, artificial intelligence (AI)-based imaging was performed to determine sodium intake in these patients. OBJECTIVE: The applicability of a diet management system was evaluated using AI-based imaging to assess the sodium content of diets prescribed for hospitalized patients. METHODS: Based on the information on the already investigated nutrients and quantity of food, consumed sodium was analyzed through photographs obtained before and after a meal. We used a hybrid model that first leveraged the capabilities of the You Only Look Once, version 4 (YOLOv4) architecture for the detection of food and dish areas in images. Following this initial detection, 2 distinct approaches were adopted for further classification: a custom ResNet-101 model and a hyperspectral imaging-based technique. These methodologies focused on accurate classification and estimation of the food quantity and sodium amount, respectively. The 24-hour urine sodium (UNa) value was measured as a reference for evaluating the sodium intake. RESULTS: Results were analyzed using complete data from 25 participants out of the total 54 enrolled individuals. The median sodium intake calculated by the AI algorithm (AI-Na) was determined to be 2022.7 mg per day/person (adjusted by administered fluids). A significant correlation was observed between AI-Na and 24-hour UNa, while there was a notable disparity between them. A regression analysis, considering patient characteristics (eg, gender, age, renal function, the use of diuretics, and administered fluids) yielded a formula accounting for the interaction between AI-Na and 24-hour UNa. Consequently, it was concluded that AI-Na holds clinical significance in estimating salt intake for hospitalized patients using images without the need for 24-hour UNa measurements. The degree of correlation between AI-Na and 24-hour UNa was found to vary depending on the use of diuretics. CONCLUSIONS: This study highlights the potential of AI-based imaging for determining sodium intake in hospitalized patients.
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Background: This study aimed to evaluate the outcome of repeat cerclage (RC) in singleton pregnancies with prolapsed membranes following a prior cerclage and analyze predictive factors for delivery at ≥26 weeks of gestation following RC. Materials and methods: Patients who underwent RC between 2010 and 2020 at the Hallym University Medical Center were reviewed. Women with singleton pregnancies with prolapsed membranes following prior cerclage were candidates for RC. We analyzed the characteristics, pregnancy outcomes, perioperative clinical and laboratory findings, and postoperative cervical length (CL) to identify the factors for predicting delivery at ≥26 weeks following RC. Results: Thirty-five women with RC were identified; the median gestational age (GA) at a prior cerclage was 14 weeks, the average GA at RC was 21 + 3 weeks, and the median GA at delivery following RC was 26 + 2 weeks. Patients were divided into two groups based on their delivery status at 26 weeks: 17 women delivered at <26 weeks (range, 18 + 4-25 + 6 weeks) (Group A) and 18 women delivered at ≥26 weeks (range, 26 + 2-40 + 3 weeks) (Group B). The median GA at delivery in group A was 22 + 4 weeks, whereas that in group B was 33 + 4 weeks (p < 0.001). No differences in preoperative clinical and laboratory findings were observed between the two groups. However, the postoperative CL in group A was significantly shorter than that in group B (12 mm vs. 21.5 mm, p < 0.001). The ROC curve of postoperative CL predicting delivery at ≥26 weeks showed an AUC of 0.843; a CL of 20 mm showed a sensitivity of 61.1% and a specificity of 100%. Conclusion: RC may prolong singleton pregnancies with prolapsed membranes following prior cerclage. A postoperative CL ≥20 mm may predict the success of RC.
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Background: Chronic idiopathic hypophosphatemia (CIH) induced by X-linked hypophosphatemic rickets or tumor-induced osteomalacia is a rare inherited or acquired disorder. However, due to its rarity, little is known about the epidemiology and natural course of CIH. Therefore, we aimed to identify the prevalence and long-term health outcomes of CIH patients. Methods: Using the Korean Health Insurance Review and Assessment claims database, we evaluated the incidence of hypophosphatemia initially diagnosed from 2003 to 2018. After excluding secondary conditions that could change serum phosphorus levels, we identified 154 patients (76 men and 78 women) with non-secondary and non-renal hypophosphatemia. These hypophosphatemic patients were compared at a ratio of 1:10 with age-, sex-, and index-year-matched controls (n = 1,540). Results: In the distribution of age at diagnosis, a large peak was observed in patients aged 1-4 years and small peaks were observed in ages from 40-70 years. The age-standardized incidence rate showed non-statistically significant trend from 0.24 per 1,000,000 persons in 2003 to 0.30 in 2018. Hypophosphatemic patients had a higher risk of any complication (adjusted hazard ratio [aHR], 2.17; 95% confidence interval [CI], 1.67-2.69) including cardiovascular outcomes, chronic kidney disease, hyperparathyroidism, osteoporotic fractures, periodontitis, and depression. Hypophosphatemic patients also had higher risks of mortality and hospitalization than the controls (aHR, 3.26; 95% CI, 1.83-5.81; and aHR, 2.49; 95% CI, 1.97-3.16, respectively). Conclusion: This first nationwide study of CIH in South Korea found a bimodal age distribution and no sex differences among patients. Hypophosphatemic patients had higher risks of complications, mortality, and hospitalization compared to age- and sex-matched controls.
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Raquitismo Hipofosfatêmico Familiar , Hipofosfatemia , Feminino , Humanos , Masculino , Povo Asiático , Estudos de Coortes , Raquitismo Hipofosfatêmico Familiar/complicações , Raquitismo Hipofosfatêmico Familiar/epidemiologia , Raquitismo Hipofosfatêmico Familiar/mortalidade , Hipofosfatemia/epidemiologia , Hipofosfatemia/etiologia , Hipofosfatemia/mortalidade , Morbidade , Lactente , Pré-Escolar , Adulto , Pessoa de Meia-Idade , Idoso , República da CoreiaRESUMO
OBJECTIVES: To evaluate the influence of myoma characteristics on cesarean myomectomy and to demonstrate its additional advantages. METHODS: Retrospective data were collected from 292 women with myomas who had undergone cesarean section at Kangnam Sacred Heart Hospital between 2007 and 2019. We performed subgroup analysis according to the type, weight, number, and size of myomas. Preoperative and postoperative hemoglobin levels, operative time, estimated blood loss, length of hospital stay, incidence of transfusion, uterine artery embolization, ligation, hysterectomy, and postoperative complications were compared among subgroups. RESULTS: There were 119 patients who had cesarean myomectomy and 173 who had cesarean section only. An increase in postoperative hospitalization and operation time was observed in the cesarean myomectomy group compared to that in the caesarean section only group (mean difference, 0.7 days, p = 0.01, 13.5 minutes, p <0.001). Estimated blood loss, hemoglobin differences, and transfusion rates were higher in the cesarean myomectomy than in the cesarean section only group. There were no differences in postoperative complications (fever, bladder injury, and ileus) between the two groups. No hysterectomy cases were reported in the cesarean myomectomy group. In subgroup analysis, the larger and heavier the myoma, the higher the risk of bleeding that led to transfusion. Estimated blood loss, differences in hemoglobin, and transfusion rate increased depending on myoma size and weight. A significant increase in postoperative hospitalization was observed in women with larger and heavier myomas. However, there was no statistical difference among the three types of myomas. CONCLUSION: In cesarean myomectomy, larger (≥ 10 cm), and heavier myomas (≥ 500 g), were associated with postoperative outcomes, but not the number or type of myoma. The safety of cesarean myomectomy is not inferior to that of caesarean section only, considering its positive effects such as gynecological symptom relief and avoidance of the next surgery.
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Laparoscopia , Leiomioma , Mioma , Miomectomia Uterina , Neoplasias Uterinas , Feminino , Humanos , Gravidez , Miomectomia Uterina/efeitos adversos , Leiomioma/cirurgia , Leiomioma/epidemiologia , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/epidemiologia , Cesárea/efeitos adversos , Estudos Retrospectivos , Mioma/etiologia , Mioma/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Fatores de Risco , Laparoscopia/efeitos adversosRESUMO
Purpose: To describe the parapapillary choroidal microvasculature dropout (CMvD) in glaucomatous eyes without ß-zone parapapillary atrophy (ß-PPA) and compare its characteristics with that of CMvD with ß-PPA. Methods: Peripapillary choroidal microvasculature was evaluated on en face images obtained using optical coherence tomography angiography. CMvD was defined as a focal sectoral capillary dropout with no visible microvascular network identified in the choroidal layer. Peripapillary and optic nerve head structures, including the presence of ß-PPA, peripapillary choroidal thickness and lamina cribrosa curvature index were evaluated using the images obtained by enhanced depth-imaging optical coherence tomography. Results: The study included 100 glaucomatous eyes with CMvD (25 without and 75 with ß-PPA) and 97 eyes without CMvD (57 without and 40 with ß-PPA). Regardless of the presence of ß-PPA, eyes with CMvD tended to have a worse visual field at a given RNFL thickness than eyes without CMvD, with patients having eyes with CMvD having lower diastolic blood pressure and more frequent cold extremities than patients with eyes lacking CMvD. Peripapillary choroidal thickness was significantly smaller in eyes with than without CMvD, but was not affected by the presence of ß-PPA. ß-PPA without CMvD was not associated with vascular variables. Conclusions: CMvD were found in the absence of ß-PPA in glaucomatous eyes. CMvDs had similar characteristics in the presence and absence of ß-PPA. Clinical and optic nerve head structural characteristics potentially relevant to compromised optic nerve head perfusion were dependent on the presence of CMvD, rather than the presence of ß-PPA.
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Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Pressão Intraocular , Corioide/irrigação sanguínea , Atrofia/patologia , Tomografia de Coerência Óptica/métodos , Microvasos/patologia , Glaucoma/patologiaRESUMO
PURPOSE: The purpose of this study was to report a case with bilateral paravascular inner retinal defects (PIRDs) enlarging with progressive myopia, which had different structural characteristics from the glaucomatous retinal nerve fiber layer (RNFL) defect. PATIENTS AND METHODS: A 10-year-old girl with high myopia was referred to a glaucoma clinic for evaluation of RNFL defects shown in color fundus photographs. Fundus photographs and optical coherence tomography examinations were serially reviewed to examine the changes in the RNFL. RESULTS: Cleavage of inner retinal layers involving the layers deeper than the RNFL was identified in optical coherence tomography, which appeared and enlarged in both eyes along with progressive myopia and axial elongation during the follow-up period of 8 years. CONCLUSIONS: PIRD developed and enlarged with progressive myopia and axial elongation in childhood. It should be differentiated from the widening of RNFL defect shown with glaucoma progression.
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Glaucoma , Miopia Degenerativa , Doenças do Nervo Óptico , Doenças Retinianas , Feminino , Humanos , Criança , Miopia Degenerativa/complicações , Miopia Degenerativa/diagnóstico , Pressão Intraocular , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/etiologia , Células Ganglionares da Retina , Tomografia de Coerência Óptica/métodos , Fibras NervosasRESUMO
BACKGROUND: To compare the ability of multicolor imaging (MCI) with red-free fundus photography (RFP) to detect glaucomatous retinal nerve fiber layer (RNFL) thinning. METHODS: A total of 127 eyes of 79 patients with glaucoma underwent MCI using blue light, RFP, and circumpapillary optical coherence tomography (OCT) scanning on the same day. Angular location and width of the RNFL defects (RNFLDs) identified on the MCI and RFP were independently measured, and compared with those of RNFL thinning indicated by abnormal color codes on OCT. RESULTS: The angular location and width of the RNFLDs determined by both MCI and RFP were well correlated with those of RNFL thinning determined by OCT (all P ≤ 0.013). The correlation of angular width with OCT was significantly stronger for MCI than for RFP (R = 0.708 vs. R = 0.616, P = 0.009). The superiority of MCI to RFP in the detection of OCT-determined RNFL thinning was significant in the inferior (P = 0.025) and marginally significant in the superior (P = 0.084) hemisectors. Thinner RNFL and longer axial length were significantly associated with better visualization of RNFLD by MCI than by RFP, respectively in the superior (OR = 0.948, P = 0.048) and inferior (OR = 1.490, P = 0.012) hemisectors. CONCLUSIONS: RNFLD on MCI correlated well with OCT measurement of RNFL thinning in eyes with glaucoma. MCI performed better than conventional RFP in the detection of OCT-determined RNFL thinning, specifically in eyes with thinner RNFL and those with myopia. MCI may be more useful than conventional RFP in evaluating glaucomatous RNFL thinning.
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Glaucoma , Doenças do Nervo Óptico , Fotoquimioterapia , Humanos , Doenças do Nervo Óptico/diagnóstico , Pressão Intraocular , Células Ganglionares da Retina , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Glaucoma/diagnóstico , Fotografação , Tomografia de Coerência Óptica/métodos , Fibras NervosasRESUMO
This study aimed to compare adverse reactions following BNT162b2 and influenza vaccinations in healthcare workers. This study included healthcare workers who received the BNT162b2 vaccine and/or inactivated influenza vaccine, quadrivalent (IIV4), on 18-29 October 2021 at a tertiary hospital in Korea. IIV4 was administered and BNT162b2 was subsequently administered one week later. The participants responded to a mobile questionnaire regarding adverse events. The overall adverse reaction rates were 90.6% in the BNT162b2 + IIV4 group, 90.4% in the BNT162b2 alone group, and 44.1% in the IIV4 alone group (p < 0.001). Fever occurred in 19.5%, 26.9%, and 3.3% of participants in the BNT162b2 + IIV4, BNT162b2 alone, and IIV4 alone groups, respectively (p < 0.001). The most common local and systemic adverse reactions were injection site pain (65.0%) and fatigue (58.6%), respectively. Injection-site pain was experienced by 88.7%, 88.5%, and 37.5% of the BNT162b2 + IIV4, BNT162b2 alone, and IIV4 alone groups, respectively (p < 0.001). Fatigue was experienced by 74.8%, 78.8%, and 38.6% of the BNT162b2 + IIV4, BNT162b2 alone, and IIV4 alone groups, respectively (p < 0.001). Adverse reactions occurred at a significantly higher frequency after BNT162b2 than after IIV4. The frequency of adverse reactions one week after vaccination with IIV4 and BNT162b2 was not different from that after vaccination with BNT162b2 alone. Therefore, coadministration of influenza vaccine with BNT162b2 can be expected to be safe.
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An aberrant late sodium current (INa,Late) caused by a mutation in the cardiac sodium channel (Nav1.5) has emerged as a contributor to electrical remodeling that causes susceptibility to atrial fibrillation (AF). Although downregulation of phosphoinositide 3-kinase (PI3K)/Akt signaling is associated with AF, the molecular mechanisms underlying the negative regulation of INa,Late in AF remain unclear, and potential therapeutic approaches are needed. In this work, we constructed a tachypacing-induced cellular model of AF by exposing HL-1 myocytes to rapid electrical stimulation (1.5 V/cm, 4 ms, 10 Hz) for 6 h. Then, we gathered data using confocal Ca2+ imaging, immunofluorescence, patch-clamp recordings, and immunoblots. The tachypacing cells displayed irregular Ca2+ release, delayed afterdepolarization, prolonged action potential duration, and reduced PI3K/Akt signaling compared with controls. Those detrimental effects were related to increased INa,Late and were significantly mediated by treatment with the INa,Late blocker ranolazine. Furthermore, decreased PI3K/Akt signaling via PI3K inhibition increased INa,Late and subsequent aberrant myocyte excitability, which were abolished by INa,Late inhibition, suggesting that PI3K/Akt signaling is responsible for regulating pathogenic INa,Late. These results indicate that PI3K/Akt signaling is critical for regulating INa,Late and electrical remodeling, supporting the use of PI3K/Akt-mediated INa,Late as a therapeutic target for AF.
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Fibrilação Atrial , Remodelamento Atrial , Humanos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinase/farmacologia , Remodelamento Atrial/fisiologia , Sódio , Miócitos Cardíacos/fisiologia , Potenciais de Ação , Átrios do CoraçãoRESUMO
We compare the outcomes of physical examination-indicated cerclage (PEIC) between singleton and twin pregnancies and analyze predictive factors for preterm birth < 28 weeks of gestation. Patients who underwent PEIC at our center were reviewed. We compared perinatal outcomes between singleton and twin pregnancies. The primary outcome was delivery before 28 weeks of gestation. Also, we analyzed perioperative clinical, laboratory, and sonographic findings to determine the risk factors for predicting preterm birth < 28 weeks. The rate of preterm birth < 28 weeks was not significantly different. Also, neonatal outcomes were not different. Also, we compared the outcomes according to GA (gestational age) at delivery before (Group A) or after (Group B) 28 weeks, which is the primary outcome. In perioperative findings, group A was likely to have more advanced cervical dilatation, bulging membranes into the vagina, positive fFN or IGFBP-1, and shorter postoperative CL (cervical length) than group B. Also, positive fFN or IGFBP-1 and postoperative CL < 21.6 mm were independently associated with a higher risk of preterm birth < 28 weeks. These findings provide the effectiveness of PEIC with twin pregnancy as well as singleton pregnancy and helpful predictive methods that might effectively identify women at high risk of preterm birth < 28 weeks following PEIC.
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The objective of this study was to determine whether multi-microRNA analysis using a combination of four microRNA biomarkers (miR-1246, 202, 21, and 219B) could improve the diagnostic performance of mammography in determining breast cancer risk by age group (under 50 vs. over 50) and distinguish breast cancer from benign breast diseases and other cancers (thyroid, colon, stomach, lung, liver, and cervix cancers). To verify breast cancer classification performance of the four miRNA biomarkers and whether the model providing breast cancer risk score could distinguish between benign breast disease and other cancers, the model was verified using nonlinear support vector machine (SVM) and generalized linear model (GLM) and age and four miRNA qRT-PCR analysis values (dCt) were input to these models. Breast cancer risk scores for each Breast Imaging-Reporting and Data System (BI-RADS) category in multi-microRNA analysis were analyzed to examine the correlation between breast cancer risk scores and mammography categories. We generated two models using two classification algorithms, SVM and GLM, with a combination of four miRNA biomarkers showing high performance and sensitivities of 84.5% and 82.1%, a specificity of 85%, and areas under the curve (AUCs) of 0.967 and 0.965, respectively, which showed consistent performance across all stages of breast cancer and patient ages. The results of this study showed that this multi-microRNA analysis using the four miRNA biomarkers was effective in classifying breast cancer in patients under the age of 50, which is challenging to accurately diagnose. In addition, breast cancer and benign breast diseases can be classified, showing the possibility of helping with diagnosis by mammography. Verification of the performance of the four miRNA biomarkers confirmed that multi-microRNA analysis could be used as a new breast cancer screening aid to improve the accuracy of mammography. However, many factors must be considered for clinical use. Further validation with an appropriate screening population in large clinical trials is required. This trial is registered with (KNUCH 2022-04-036).
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Neoplasias da Mama , Doença da Mama Fibrocística , MicroRNAs , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , MicroRNAs/genética , Mamografia/métodos , Mama , BiomarcadoresRESUMO
Background: To report the pregnancy and neonatal outcomes in patients with twin pregnancies who underwent ultrasound-indicated cerclage (UIC) and to compare them to patients with singleton pregnancies undergoing the same procedures. Methods: Patients who underwent UIC between January 2010 and December 2020 at Kangnam Sacred Heart Hospital were reviewed. We compared characteristics, pregnancy, and neonatal outcomes between patients with singleton and twin pregnancies. Results: A total of 94 women (56 singleton and 38 twin pregnancies) underwent UIC were included. The mean gestational age (GA) at cerclage and preoperative cervical length (CL) were not significantly different. Twin pregnancies were more likely to deliver at earlier median gestations than singletons (singleton, 36 + 1 weeks vs twin, 32 + 6 weeks, and p = 0.004). The frequency of preterm delivery <34 weeks in twin group was higher than in singleton group (15 (26.8%) vs 20 (52.6%) and p =0.016). However, the frequency of preterm delivery <32, <28, and <24 weeks was not significantly different between two groups. Although neonatal weights in singleton pregnancies were heavier than twin pregnancies, neonatal mortality and morbidities were not significantly different between two groups. Among various factors contributing to preterm birth, preoperative CL ≤ 15 mm was independently associated with a higher risk of preterm delivery before 34 weeks. Furthermore, pregnancy and neonatal outcomes of twin pregnancies with cervical length ≤ 15 mm are comparable with those of singleton pregnancies (GA at delivery, singleton, 35 + 1 weeks vs twin, 32 + 5 weeks, and p = 0.24; neonatal mortality, singleton, 3.4% vs twin, 4.8%, and p = 0.64). Conclusion: The pregnancy and neonatal outcomes of UIC in twin pregnancies were comparable to those in singleton pregnancies, especially when CL is ≤15 mm. UIC might be considered a safe procedure for twin pregnancies.
Assuntos
Cerclagem Cervical , Nascimento Prematuro , Gravidez , Humanos , Recém-Nascido , Feminino , Estudos de Coortes , Resultado da Gravidez , Estudos RetrospectivosRESUMO
Microneedles have emerged as a novel transdermal delivery tool that enables the delivery of various products such as drugs, vaccines, or cosmetic ingredients. Although the demand for solid microneedles composed of biocompatible polymer is increasing, the manufacture of microneedles using poly-lactic acid (PLA) with rapid drug-releasing is yet to be established and the process is still in its infancy. Here, we propose a novel strategy for the fabrication of PLA solid microneedles which enable a drug to be burst-released based on a solvent-casting process. This approach offers extreme simplicity, broad geometric capability, cost-effectiveness, and scalability based on high fidelity-replicas. It was verified that microneedles of various heights (250-500 µm) could be fabricated with appropriate mechanical strength to penetrate the stratum corneum layer of skin. By adding sugar in the composition of PLA microneedle, it was observed that both hydrophilic and hydrophobic drugs can be rapidly released within 30 min. Our burst drug-releasing PLA microneedle having both characteristics of solid microneedle and soluble microneedle and its fabrication approach based on solvent-casting will contribute to getting microneedle technology close to commercialization and beyond existing technical limitations.
RESUMO
This study aimed to present the prognosis after minor acute ischemic stroke (AIS) or transient ischemic attack (TIA), using a definition of subsequent stroke in accordance with recent clinical trials. In total, 9,506 patients with minor AIS (National Institutes of Health Stroke Scale ≤ 5) or high-risk TIA (acute lesions or ≥ 50% cerebral artery steno-occlusion) admitted between November 2010 and October 2013 were included. The primary outcome was the composite of stroke (progression of initial event or a subsequent event) and all-cause mortality. The cumulative incidence of stroke or death was 11.2% at 1 month, 13.3% at 3 months and 16.7% at 1 year. Incidence rate of stroke or death in the first month was 12.5 per 100 person-months: highest in patients with large artery atherosclerosis (17.0). The risk of subsequent events shortly after a minor AIS or high-risk TIA was substantial, particularly in patients with large artery atherosclerosis.