RESUMEN
The prevalence of tick-borne pathogens (TBP), Orientia tsutsugamushi, Rickettsia and Borrelia spp. in wild small animals, namely wild rodents, is now widely investigated. This study is to present the prevalence and distribution of O. tsutsugamushi, Rickettsia and Borrelia spp. in wild small animals and ticks collected from Gyeonggi and Gangwon provinces, Republic of Korea (ROK) in 2014. A total of 131 wild small animals, rodents and shrews, and 2,954 ticks were collected from Gyeonggi and Gangwon provinces from May to November 2014. The wild small animals (KR1-9) and ticks (K1-17) were grouped in accordance with capture dates and locations. Among the wild small animals, a total of 393 tissues and blood samples were extracted from six selected small animal series (KR1-3, KR6-8). Also, each date and location-grouped ticks were identified for its species and pooled according to the stage of development. Molecular identification for Rickettsia, Orientia, and Borrelia species was performed using polymerase chain reaction (PCR). To detect TBPs among wild small animals and ticks, primer sets targeting the 56 kDa protein encoding gene of Orientia spp., outer membrane protein B gene (OmpB) of Rickettsia spp., and 5S-23S intergenic spacer region (IGS) gene of Borrelia spp. were used. Of the 393 wild small animals' blood and tissue samples, 199 (50.6%) were positive for Orientia spp., 158 (40.2%) were positive for Borrelia spp., and 55 (14.0%) were positive for Rickettsia spp. Moreover, a total of 14 tick pools (n = 377) was positive for Rickettsia spp. (n=128, 34.0%) and Borrelia spp. (n=33, 8.8%). High prevalence of Orientia spp. and Rickettsia spp. in rodents and shrews were observed. This study presents significant insights by presenting data collected in 2014 that the prevalence of TBP was already high in mid 2010s. This study highlights the sustainable routine surveillance model for TBP.
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Borrelia , Orientia tsutsugamushi , Rickettsia , Roedores , Musarañas , Garrapatas , Animales , Musarañas/parasitología , Musarañas/microbiología , Roedores/microbiología , Roedores/parasitología , Rickettsia/aislamiento & purificación , Rickettsia/genética , República de Corea/epidemiología , Orientia tsutsugamushi/genética , Orientia tsutsugamushi/aislamiento & purificación , Borrelia/aislamiento & purificación , Borrelia/genética , Garrapatas/microbiología , Enfermedades por Picaduras de Garrapatas/epidemiología , Enfermedades por Picaduras de Garrapatas/microbiología , Enfermedades por Picaduras de Garrapatas/veterinaria , Reacción en Cadena de la Polimerasa , Animales Salvajes/microbiología , Animales Salvajes/parasitología , Tifus por Ácaros/epidemiología , Tifus por Ácaros/veterinaria , Tifus por Ácaros/microbiologíaAsunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos , Hospitales , Microbiología del Agua , República de Corea/epidemiología , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Humanos , Hospitales/estadística & datos numéricos , Antibacterianos/farmacología , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/epidemiología , Carbapenémicos/farmacologíaRESUMEN
Human milk oligosaccharides (HMO) affect gut microbiota during neonatal development, particularly with respect to the immune system. Bovine milk-based infant formulas have low oligosaccharide contents. Thus, efforts to fortify infant formulas with HMO are being undertaken. Two major HMO, 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), exert anti-inflammatory effects; however, the associations between anti-inflammatory effects induced by 2'-FL and 6'-SL cotreatment and gut microbiota composition and metabolite modulation remain unclear. Therefore, in this study, we evaluated the effects of a mixture of these HMO. To determine the optimal HMO ratio for anti-inflammatory effects and elucidate its mode of action, LPS-induced inflammatory HT-29 epithelial cells and intestinal-inflamed suckling mice were treated with various mixtures of 2'-FL and 6'-SL. A 2'-FL:6'-SL ratio of 5:1 was identified as the most effective pretreatment HMO mixture in vitro; thus, this ratio was selected and used for low-, middle-, and high-dose treatments for subsequent in vivo studies. In vivo, high-dose HMO treatment restored LPS-induced inflammation symptoms, such as BW loss, colon length reduction, histological structural damage, and intestinal gene expression related to inflammatory responses. High-dose HMO was the only treatment that modulated the major phyla Bacteroidetes and Firmicutes and the genera Ihubacter, Mageeibacillus, and Saccharofermentans. These changes in microbial composition were correlated with intestinal inflammation-related gene expression and short-chain fatty acid production. To our knowledge, our study is the first to report the effects of Ihubacter, Mageeibacillus, and Saccharofermentans on short-chain fatty acid levels, which can subsequently affect inflammatory cytokine and tight junction protein levels. Conclusively, the HMO mixture exerted anti-inflammatory effects through changes in microbiota and metabolite production. These findings suggest that supplementation of infant formula with HMO may benefit formula-fed infants by forming unique microbiota contributing to neonatal development.
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Lipopolisacáridos , Oligosacáridos , Ratones , Animales , Oligosacáridos/farmacología , Inflamación/tratamiento farmacológico , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Trisacáridos/farmacología , Lactosa/análogos & derivadosRESUMEN
This study aimed to detect signals of adverse drug reactions (ADRs) associated with biological disease-modifying antirheumatic drugs (DMARDs) and targeted therapies in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients. Utilizing the KOrean College of Rheumatology BIOlogics & Targeted Therapy Registry (KOBIO) data, we calculated relative risks, excluded previously reported drug-ADR pairs, and externally validated remaining pairs using US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and single centre's electronic health records (EHR) data. Analyzing data from 2279 RA and 1940 AS patients, we identified 35 significant drug-ADR pairs in RA and 26 in AS, previously unreported in drug labels. Among the novel drug-ADR pairs from KOBIO, 15 were also significant in the FAERS data. Additionally, 2 significant drug-laboratory abnormality pairs were found in RA using CDM MetaLAB analysis. Our findings contribute to the identification of 14 novel drug-ADR signals, expanding our understanding of potential adverse effects related to biological DMARDs and targeted therapies in RA and AS. These results emphasize the importance of ongoing pharmacovigilance for patient safety and optimal therapeutic interventions.
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Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Espondilitis Anquilosante , Humanos , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/inducido químicamente , Preparaciones Farmacéuticas , Datos de Salud Recolectados Rutinariamente , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inducido químicamente , Antirreumáticos/efectos adversos , Sistema de Registros , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Productos Biológicos/efectos adversos , República de Corea/epidemiologíaRESUMEN
BACKGROUND: A series of qualitative studies conducted by the OMERACT Myositis Working Group identified pain interference, fatigue, and physical function as highly important life impact domains for adults with idiopathic inflammatory myositis (IIM). In this study, our goal was to assess the responsiveness and minimal important difference of PROMIS pain interference (6a), fatigue (7a), and physical function (8b). METHODS: Adults with IIM from USA, Netherlands, Korea, Sweden, and Australia with two "clinical" visits were enrolled in this prospective study. Anchor questions on a Likert scale were collected at baseline, and manual muscle testing (MMT), physician and patient reported global disease activity, and PROMIS instruments were collected at both visits. Responsiveness was assessed with i) ANOVA, ii) paired t-test, effect size and standardized response mean, and iii) Pearson correlation. Minimal important difference (MID), minimal important change (MIC) and minimal detectable change (MDC) values were calculated. RESULTS: 114 patients with IIM (median age 60, 60 % female) completed both visits. Changes in PROMIS instruments were significantly different among anchor categories. Patients who reported improvement had a significant improvement in their PROMIS scores with at least medium effect size, while patients who reported worsening and stability did not show a significant change with weak effect size. PROMIS instruments had weak to moderate correlations with MMT, patient and physician global disease activity. MID was approximately 2-3 points for Pain Interference and 3-4 points for Fatigue and Physical Function forms based on the method used. MIC was approximately 4-5 for improvement of all the instruments, while MDC was 1.7-2 points for Pain Interference and Physical Function and 3.2-3.9 for Fatigue. CONCLUSION: This study provides evidence towards the responsiveness of the PROMIS instruments in a large international prospective cohort of adults with IIM supporting their use as PROMs in adult myositis.
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Miositis , Medición de Resultados Informados por el Paciente , Adulto , Humanos , Femenino , Masculino , Estudios Prospectivos , Dolor , Miositis/complicaciones , Miositis/diagnóstico , Fatiga/diagnóstico , Fatiga/etiologíaRESUMEN
OBJECTIVE: This study aimed to explore socio-economic factors and medical conditions that affect regular stomach cancer (SC) screening among Korean adults. STUDY DESIGN: This was a retrospective observational study. METHODS: Study subjects were 5545 adults aged ≥40 years who participated in the 2007-2012 Korean National Health and Nutrition Examination Survey and were followed up to year 2017 based on data linking to the Korean National Health Insurance Service and Korean Health Insurance Review and Assessment. Socio-economic factors included sex, age, residential area, education, occupation, marital status, disability, public and private health insurance, service through local public health organizations, history of cancer except for SC, and family history of SC. Medical factors included six gastric lesions with the possibility of facilitating SC screening, including benign gastric neoplasm, chronic atrophic gastritis, gastric polyp, Helicobacter pylori infection, intestinal metaplasia, and peptic ulcers. The outcome was adherence to SC screening, which was divided into non-adherence, irregular adherence, and regular adherence. RESULTS: After adjusting for the effects of socio-economic factors, multivariate ordinal logistic regression revealed that participants with a history of four types of gastric lesions were more likely to regularly participate in SC screening: chronic atrophic gastritis (odds ratio [OR] 1.567; 95% confidence interval [CI] = 1.276-1.923), gastric polyps (OR 1.565; 95% CI = 1.223-2.003), H. pylori infection (OR 1.637; 95% CI = 1.338-2.003), and peptic ulcer (OR 2.226; 95% CI 1.750-2.831). CONCLUSIONS: To improve participation in SC screening, it is necessary to implement personalized strategies for individuals at risk for gastric cancer in addition to population-based strategies for vulnerable groups.
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Pólipos Adenomatosos , Gastritis Atrófica , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Adulto , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiología , Gastritis Atrófica/patología , Estudios Retrospectivos , Estudios Longitudinales , Detección Precoz del Cáncer , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/patología , Encuestas Nutricionales , Salud Pública , Factores Económicos , República de Corea/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: The severity of non-tuberculous mycobacterial pulmonary disease (NTM-PD) can be classified based on an assessment of the patient´s body mass index, age, presence of cavity, erythrocyte sediment rate and sex (BACES). In this study, changes in lung function according to disease severity were analysed.METHODS: Patients with NTM-PD who underwent at least two lung function tests between 1 January 2011 and 31 December 2021, were classified according to their BACES score into mild (0-1), moderate (2-3) and severe (4-5) groups, and changes in lung function were assessed using BACES scores.RESULTS: A total of 354 patients were divided into three groups: mild (n = 108), moderate (n = 216) and severe (n = 30). As disease severity increased, the decrease in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) was greater: respectively 26.4 mL/year, 31.3 mL/year and 35.7 mL/year in case of FEV1 (P for trend = 0.002); 18.9 mL/year, 25.5 mL/year and 48.9 mL/year in case of FVC (P for trend = 0.002); and 0.7%/year, 1.3%/year and 2.5%/year for DLCO (P for trend = 0.023) in the mild, moderate and severe groups.CONCLUSION: The decrease in lung function in NTM-PD was correlated with disease severity.
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Enfermedades Pulmonares , Pulmón , Humanos , Micobacterias no Tuberculosas , Volumen Espiratorio Forzado , Capacidad Vital , Gravedad del Paciente , Capacidad de Difusión PulmonarRESUMEN
BACKGROUND: There have been limited data on the risk of onward transmission from individuals with Omicron variant infections who return to work after a 5-day isolation. AIM: To evaluate the risk of transmission from healthcare workers (HCWs) with Omicron variant who returned to work after a 5-day isolation and the viable-virus shedding kinetics. METHODS: This investigation was performed in a tertiary care hospital, Seoul, South Korea. In a secondary transmission study, we retrospectively reviewed the data of HCWs confirmed as COVID-19 from March 14th to April 3rd, 2022 in units with five or more COVID-19-infected HCWs per week. In the viral shedding kinetics study, HCWs with Omicron variant infection who agreed with daily saliva sampling were enrolled between February and March, 2022. FINDINGS: Of the 248 HCWs who were diagnosed with COVID-19 within 5 days of the return of an infected HCW, 18 (7%) had contact with the returned HCW within 1-5 days after their return. Of these, nine (4%) had an epidemiologic link other than with the returning HCW, and nine (4%) had contact with the returning HCW, without any other epidemiologic link. In the study of the kinetics of virus shedding (N = 32), the median time from symptom onset to negative conversion of viable virus was four days (95% confidence interval: 3-5). CONCLUSION: Our data suggest that the residual risk of virus transmission after 5 days of isolation following diagnosis or symptom onset is low.
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COVID-19 , Humanos , SARS-CoV-2 , Estudios Retrospectivos , Cinética , Personal de SaludRESUMEN
BACKGROUND: Hospital infection control measures against coronavirus disease 2019 (COVID-19) are often based on expert discretion due to the lack of detailed guidelines. AIM: To survey the current strategies for preventing the transmission of COVID-19 in medical institutions. METHODS: Thirteen key issues related to the prevention of COVID-19 transmission within medical institutions were selected via discussion among infectious diseases specialists, and related critical questions were obtained following a review of national-level guidelines in government databases. Six hospitals had an open survey between 11th and 25th August 2020 to provide responses to these topics. An online questionnaire developed from these data was sent to infection control teams at 46 hospitals in South Korea between 31st January 2021 and 20th February 2021. FINDINGS: All 46 hospitals responded to the survey. All operated screening clinics, but 89.1% (41/46) allowed symptomatic patients without COVID-19-associated symptoms to visit general outpatient clinics. Most hospitals (87.2%, 34/39) conducted polymerase chain reaction (PCR) tests for all hospitalized patients. Of 35/46 (76.1%) hospitals with pre-emptive isolation policies for hospitalized patients, 31 (88.6%) released patients from isolation after a single negative PCR test, while most (76.9%, 20/26) allowed shared-room accommodation for patients meeting the national criteria for release from isolation despite positive PCR results with above cycle threshold values (34.6%, 9/26), or after a certain period that satisfied the national criteria (26.9%, 7/26). CONCLUSION: Individual hospitals in South Korea are currently relying on experience to frame relevant guidelines, and responded differently to some infection control issues on hospital settings during the COVID-19 pandemic.
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COVID-19 , Humanos , COVID-19/prevención & control , Pandemias/prevención & control , SARS-CoV-2 , República de Corea/epidemiología , Hospitales , Encuestas y CuestionariosRESUMEN
BACKGROUND AND PURPOSE: Data on SAH after M2 mechanical thrombectomy are limited. We aimed to determine the prevalence of sulcal SAH after mechanical thrombectomy for M2 occlusion, its associated predictors, and the resulting clinical outcome. MATERIALS AND METHODS: The study retrospectively reviewed the data of patients with acute ischemic stroke who underwent mechanical thrombectomy for isolated M2 occlusion. The patients were divided into 2 groups according to the presence of sulcal SAH after M2 mechanical thrombectomy. Angiographic and clinical outcomes were compared. Multivariable analysis was performed to identify independent predictors of sulcal SAH and unfavorable outcome (90-day mRS, 3-6). RESULTS: Of the 209 enrolled patients, sulcal SAH was observed in 33 (15.8%) patients. The sulcal SAH group showed a higher rate of distal M2 occlusion (69.7% versus 22.7%), a higher of rate of superior division occlusion (63.6% versus 43.8%), and a higher M2 angulation (median, 128° versus 106°) than the non-sulcal SAH group. Of the 33 sulcal SAH cases, 23 (66.7%) were covert without visible intraprocedural contrast extravasation. Distal M2 occlusion (OR, 12.04; 95% CI, 4.56-35.67; P < .001), superior division (OR, 3.83; 95% CI, 1.43-11.26; P = .010), M2 angulation (OR, 1.02; 95% CI, 1.01-1.04; P < .001), and the number of passes (OR, 1.58; 95% CI, 1.22-2.09; P < .001) were independent predictors of sulcal SAH. However, covert sulcal SAH was not associated with an unfavorable outcome (P = .830). CONCLUSIONS: After mechanical thrombectomy for M2 occlusion, sulcal SAH was not uncommon and occurred more frequently with distal M2 occlusion, superior division, acute M2 angulation, and multiple thrombectomy passes (≥3). The impact of covert sulcal SAH was mostly benign and was not associated with an unfavorable outcome.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Estudios Retrospectivos , Trombectomía/efectos adversos , Trombectomía/métodos , Resultado del Tratamiento , Accidente Cerebrovascular/epidemiologíaRESUMEN
OBJECTIVE: The aim of this study is to compare the risk of venous thromboembolic events (VTE) between patients suspending and continuing estrogen therapy perioperatively, in male to female gender-affirming surgery (vaginoplasty). MATERIALS AND METHODS: The authors conducted a systematic review and meta-analysis of existing research on male to female gender-affirming study, which compared the risk of VTE among the usage of estrogen perioperatively. RESULTS: A total of 209 studies were identified as potentially eligible among PubMed, Embase, and Cochrane library databases. Among the studies, 191 studies were excluded due to their abstract inappropriateness. Out of the remaining 18 studies, only 3 articles were eligible and were finally included. Meta-analysis was performed and showed odds ratio of 0.77 (95% CI: 0.04, 14.01). CONCLUSIONS: Perioperative estrogen therapy does not increase VTE risk on male to female gender-affirming surgery. Therefore, estrogen therapy may be continued perioperatively in vaginoplasty. More prospective studies are needed.
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Personas Transgénero , Tromboembolia Venosa , Trombosis de la Vena , Estrógenos/efectos adversos , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Masculino , Tromboembolia Venosa/inducido químicamente , Tromboembolia Venosa/epidemiologíaRESUMEN
OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a pandemic and leading cause of death. Beyond the deaths directly caused by the virus and the suicides related to the psychological response to the dramatic changes as socioeconomic related to the pandemic, there might also be suicides related to the inflammatory responses of the infection. Infection induces inflammation as a cytokine storm, and there is an increasing number of studies that report a relationship between infection and suicide. MATERIALS AND METHODS: We searched the World Health Organization status report and the PubMed database for keywords (COVID-19, suicide, infection, inflammation, cytokines), and reviewed five cytokine pathways between suicide and inflammation using two meta-analyses and two observational studies starting from November 31, 2020, focusing on the relationship between suicide and inflammation by infection. First, we discussed existing evidence explaining the relationship between suicidal behaviors and inflammation. Second, we summarized the inflammatory features found in COVID-19 patients. Finally, we highlight the potential for these factors to affect the risk of suicide in COVID-19 patients. RESULTS: Patients infected with COVID-19 have high amounts of IL-1ß, IFN-γ, IP10, and MCP1, which may lead to Th1 cell response activation. Also, Th2 cytokines (e.g., IL-4 and IL-10) were increased in COVID-19 infection. In COVID-19 patients, neurological conditions, like headache, dizziness, ataxia, seizures, and others have been observed. CONCLUSIONS: COVID-19 pandemic can serve as a significant environmental factor contributing directly to increased suicide risk; the role of inflammation by an infection should not be overlooked.
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COVID-19/inmunología , Citocinas/inmunología , Suicidio , COVID-19/psicología , Humanos , Factores de Riesgo , Suicidio/psicologíaRESUMEN
BACKGROUND AND PURPOSE: Data on adjunctive intra-arterial thrombolysis during mechanical thrombectomy for refractory thrombus are sparse. The aim of this study was to evaluate the efficacy and safety of local intra-arterial urokinase as an adjunct to mechanical thrombectomy for refractory large-vessel occlusion. MATERIALS AND METHODS: We retrospectively evaluated patients with acute ischemic stroke who underwent mechanical thrombectomy for anterior circulation large-vessel occlusion between January 2016 and December 2019. Patients were divided into 2 groups based on the use of intra-arterial urokinase as an adjunctive therapy during mechanical thrombectomy for refractory thrombus: the urokinase and nonurokinase groups. Herein, refractory thrombus was defined as the target occlusion with minimal reperfusion (TICI 0 or 1) despite >3 attempts with conventional mechanical thrombectomy. The baseline characteristics, procedural outcomes, and clinical outcome were compared between the 2 groups. RESULTS: One hundred fourteen cases of refractory thrombus were identified. A total of 45 and 69 patients were in the urokinase and the nonurokinase groups, respectively. The urokinase group compared with the nonurokinase group showed a higher rate of successful reperfusion (82.2% versus 63.8%, P = .034), with lower procedural times (54 versus 69 minutes, P = .137). The rates of good clinical outcome, distal embolism, and symptomatic intracranial hemorrhage were similar between the 2 groups. The use of intra-arterial urokinase (OR = 3.682; 95% CI, 1.156-11.730; P = .027) was an independent predictor of successful reperfusion. CONCLUSIONS: The use of local intra-arterial urokinase as an adjunct to mechanical thrombectomy may be an effective and safe method that provides better recanalization than the conventional mechanical thrombectomy for refractory thrombus in patients with embolic large-vessel occlusion.
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Isquemia Encefálica , Trombolisis Mecánica , Accidente Cerebrovascular , Humanos , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía , Terapia Trombolítica , Resultado del TratamientoRESUMEN
BACKGROUND: In this study, we evaluated the association between genetic polymorphisms of 23 genes associated with gemcitabine metabolism and the clinical efficacy of gemcitabine in breast cancer patients. PATIENTS AND METHODS: This prospective, pharmacogenetic study was conducted in cooperation with a phase II clinical trial. A total of 103 genetic polymorphisms of the 23 genes involved in gemcitabine transport and metabolism were selected for genotyping. The associations of genetic polymorphisms with overall survival, progression-free survival (PFS), and 6-month PFS were analyzed. RESULTS: A total of 91 breast cancer patients were enrolled in this study. In terms of 6-month PFS, rs1044457 in CMPK1 was the most significant genetic polymorphism [55.9% for CT and TT and 78.9% for CC, P < 0.001, hazard ratio (HR): 4.444, 95% confidence interval (CI): 1.905-10.363]. For the rs693955 in SLC29A1, the median duration of PFS was 5.4 months for AA and 10.5 months for CA and CC (P = 0.002, HR: 3.704, 95% CI: 1.615-8.497). For the rs2807312 in TLE4, the median duration of PFS was 5.7 months for TT and 10.4 months for CT and CC (P = 0.005, HR: 4.948, 95% CI: 1.612-15.190). In survival analysis with a multi-gene model, the TT genotype of rs2807312 had the worst PFS regardless of other genetic polymorphisms, whereas the CA genotype of rs693955 or the CT genotype of rs2807312 without the AA genotype of rs693955 had the best PFS compared with those of other genetic groups (P < 0.001). CONCLUSIONS: Genetic polymorphisms of rs1044457 in CMPK1, rs693955 in SLC29A1, and rs2807312 in TLE4 were significantly associated with the 6-month PFS rate and/or the duration of PFS. Further studies with a larger sample size and expression study would be helpful to validate the association of genetic polymorphisms and clinical efficacy of gemcitabine.
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Neoplasias de la Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Desoxicitidina/análogos & derivados , Tranportador Equilibrativo 1 de Nucleósido , Femenino , Furanos , Humanos , Cetonas , Proteínas Nucleares/uso terapéutico , Paclitaxel/uso terapéutico , Pruebas de Farmacogenómica , Polimorfismo Genético , Estudios Prospectivos , Proteínas Represoras/uso terapéutico , GemcitabinaRESUMEN
BACKGROUND: Angiotensin-converting enzyme 2 (ACE2), a receptor targeted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the nasal mucosa. Chronic rhinosinusitis (CRS) shows diverse endotypes and is aggravated by viral infection. Whether viral stimulation and CRS endotype influence ACE2 expression remains unclear. We investigated the expression of ACE2 and the transmembrane protease, serine 2 (TMPRSS2), which mediate the entry of SARS-CoV-2 into cells, and assessed polyinosinic:polycytidylic acid (poly[I:C])-induced changes based on CRS endotype. METHODOLOGY: ACE2 and TMPRSS2 expression was evaluated based on CRS phenotype, endotype, and tissue type. Correlations between ACE2/TMPRSS2 expression and inflammatory mediators in nasal polyps (NP) were examined. Air-liquid interface culture experiments were performed to assess the effects of major cytokines or poly(I:C) stimulation on ACE2/TMPRSS2 expression in primary epithelial cells from healthy nasal mucosa, eosinophilic NP (ENP), and non-eosinophilic NP (NENP). RESULTS: In primary nasal epithelial cells, interleukin (IL)-13 decreased ACE2 expression but increased TMPRSS2. Eosinophilic CRS showed lower ACE2 expression than non-eosinophilic CRS, regardless of CRS phenotype. CRS endotype was an independent factor associated with ACE2/TMPRSS2 expression in NP. Serum and tissue eosinophilic marker levels were inversely correlated with ACE2 expression, whereas tissue neutrophilic marker levels and ACE2 expression were positively correlated in NP. ACE2 expression was suppressed in ENP tissues; however, a combination of poly(I:C) and IL-13 induced ACE2/TMPRSS2 upregulation in ENP. CONCLUSIONS: ENP tissues have lower ACE2 expression than NENP; however, viral stimulation promotes ACE2/TMPRSS2 upregulation in ENP.
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COVID-19 , Sinusitis , Enzima Convertidora de Angiotensina 2 , Humanos , Peptidil-Dipeptidasa A , SARS-CoV-2RESUMEN
Selecting an appropriate allergen-specific immunotherapy (AIT) regimen for polysensitised allergic rhinitis (AR) patients is challenging for clinicians. Although previous studies showed comparable effectiveness of single-allergen AIT with house dust mite (HDM) extract between monosensitised and polysensitised AR patients, there is no systematic review and meta-analysis demonstrating the comparable effectiveness of HDM AIT. In this meta-analysis, we analysed nine studies to compare the clinical effectiveness of HDM AIT. The primary outcome was nasal symptom score and secondary outcomes were medication and quality of life scores. The changes in nasal symptom score after HDM AIT did not significantly differ between monosensitised and polysensitised patients. The clinical effectiveness of HDM AIT regarding medication and quality of life score was not significantly different between monosensitised and polysensitised patients). In conclusion, single-allergen AIT with HDM extract showed comparable clinical effectiveness between polysensitised and monosensitised patients with AR.
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Rinitis Alérgica , Inmunoterapia Sublingual , Animales , Desensibilización Inmunológica , Humanos , Pyroglyphidae , Calidad de Vida , Rinitis Alérgica/terapia , Resultado del TratamientoRESUMEN
OBJECTIVE: We aimed to analyze clinical characteristics, treatment patterns, and prognosis of patients with reversible cerebral vasoconstriction syndrome (RCVS). MATERIALS AND METHODS: Two investigators independently searched PubMed and EMBASE, and 191 cases were included in this study. Information regarding demographics, triggering factors, brain imaging findings, treatment modalities, recurrence, and clinical outcome was collected. RESULTS: The mean age of the patients was 39.9 years, and 155 (81.2%) were female. The most common triggering factor for RCVS was an exposure to vasoactive substances (41.4%), followed by pregnancy/postpartum (20.9%), and sexual intercourse (10.5%). Multifocal stenosis (84.0%) and beading shape (82.4%) were the leading abnormal findings on angiography, while cerebral ischemic lesions (47.6%) and cerebral hemorrhage (mainly subarachnoid hemorrhage) (35.1%) were the main findings on brain computed tomography (CT)/magnetic resonance imaging (MRI). Calcium channel blockers (nimodipine/verapamil) were the most commonly used medications (44.5%) in the treatment of RCVS. Multivariate analysis identified that RCVS was precipitated by trauma/surgery/procedure (hazard ratio (HR): 3.29, 95% confidence interval (CI) (1.21-8.88), p=0.019), and presence of aphasia/neglect/apraxia during the acute phase of the disease (HR: 3.83, 95% CI (1.33-11.05), p=0.013) were found to be the two independent risk factors for residual neurological deficit after RCVS. CONCLUSIONS: In our systematic review, vasoactive substances were the most frequent triggers for RCVS, which was most commonly accompanied by angiographic findings of multifocal stenotic lesions. Patients with RCVS precipitated by trauma or surgical procedures and those with focal cortical deficits had a higher risk of residual neurological deficits, and these patients should closely be monitored.