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Importance: EGFR-variant non-small cell lung cancer (NSCLC) is associated with a high rate of central nervous system (CNS) metastases, even with treatment with first-generation or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Objective: To investigate CNS activity with lazertinib, a third-generation EGFR TKI. Design, Setting, and Participants: This multicenter single-arm, phase 2 nonrandomized controlled trial was conducted in South Korea and included patients with EGFR-variant NSCLC who had asymptomatic or mildly symptomatic brain metastases after unsuccessful treatment with first-generation or second-generation EGFR TKIs. Data were collected from June 2021 to April 2022, with a data cutoff date of December 15, 2022. Exposure: Lazertinib, 240 mg, once daily. Main Outcomes and Measures: The primary end point was intracranial objective response rate (iORR) in the evaluable population according to the Response Evaluation Criteria in Solid Tumours version 1.1 assessed by the investigators. Secondary end points included intracranial progression-free survival (iPFS) and iORR in patients with T790M-negative disease and isolated CNS progression as well as overall ORR, duration of response, intracranial duration of response, disease control rate, overall survival, cerebrospinal fluid penetration of lazertinib, and safety. Results: Among 40 included patients, 25 (63%) were women, and the median (range) age was 63 (29-85) years. A total of 38 patients were evaluable for tumor response, including 12 patients with leptomeningeal metastases. At data cutoff, the median (range) follow-up was 13.6 (2.9-17.7) months. The iORR for the evaluable population was 55% (21 of 38; 95% CI, 38.3-71.4); for patients with T790M-positive disease, 80% (4 of 5; 95% CI, 28.4-99.5); for patients with T790M-negative disease, 43% (9 of 21; 95% CI, 21.8-66.0); and for patients with T790M-unknown disease, 67% (8 of 12; 95% CI, 34.9-90.1). The median iPFS was 15.8 months (95% CI, 15.2-not reached) for the evaluable population, 15.2 months (95% CI, 4.2-not reached) for the T790M-positive subgroup, 15.4 months (95% CI, 7.9-not reached) for the T790M-negative subgroup, and 18.0 months (95% CI, 3.9-not reached) for the T790M-unknown subgroup. The cerebrospinal fluid penetration rate of lazertinib was 46.2% (95% CI, 10.0-49.6), providing further support for its mechanism of intracranial response. Most adverse events were grade 1 or 2. Conclusions and Relevance: In this study, lazertinib had substantial CNS activity, regardless of T790M status, against the progression of intracranial metastases with or without leptomeningeal metastases after unsuccessful treatment with first-generation or second-generation EGFR TKIs in patients with metastatic EGFR-variant NSCLC. These results suggest that using lazertinib instead of brain local treatment could be a potential strategy in patients with EGFR-variant NSCLC whose CNS metastases progressed after prior EGFR TKI treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT05326425.
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Optimal fluid management during major surgery is of considerable concern to anesthesiologists. Although crystalloids are the first choice for fluid management, the administration of large volumes of crystalloids is associated with poor postoperative outcomes. Albumin can be used for fluid management and may protect renal function. However, data regarding the effects of albumin administration on kidney function are conflicting. As such, the present study aimed to investigate the effect of albumin administration on renal function in patients undergoing major surgery and compare its effects with those of crystalloid fluid. The Embase, Medline, Web of Science, Cochrane Library, and KoreaMed databases were searched for relevant studies. The primary endpoint of the meta-analysis was the incidence of postoperative kidney injury, including acute kidney injury and renal replacement therapy. Twelve studies comprising 2311 patients were included; the primary endpoint was analyzed in four studies comprising 1749 patients. Perioperative albumin levels in patients undergoing major surgery did not significantly influence kidney dysfunction (p = 0.98). Postoperative fluid balance was less positive in patients who underwent major surgery and received albumin than in those who received crystalloids. Owing to the limitations of this meta-analysis, it remains unclear whether albumin administration during major surgery is better than crystalloid fluid for improving postoperative renal function.
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Complicaciones Posoperatorias , Humanos , Complicaciones Posoperatorias/etiología , Riñón/efectos de los fármacos , Riñón/fisiopatología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Fluidoterapia/métodos , Soluciones Cristaloides/administración & dosificación , Albúminas/administración & dosificación , Periodo Posoperatorio , Albúmina Sérica Humana/administración & dosificaciónRESUMEN
Air pollution and heavy metal exposure are emerging public health concerns. Prenatal exposure to air pollutants and heavy metals has been implicated in the development of congenital heart disease (CHD). However, the relationship between exposure to airborne heavy metals and CHD has not yet been investigated. Therefore, in this large population-based study, we investigated the association between air pollutants, including airborne heavy metals, and the risk of CHD using national health insurance claims data from South Korea. Data regarding 1,129,442 newborns and their mothers were matched with air pollutant levels during the first 8 weeks of gestation. In the five-air pollutant model, we found significant positive correlations between prenatal exposure to sulfur dioxide (SO2; odds ratio [OR] 6.843, 95% confidence interval [CI] 5.746-8.149) and cadmium (Cd; OR 1.513, 95% CI 1.187-1.930) and the risk of ventricular septal defects in newborns. This study highlights the association between prenatal exposure to air pollutants, including airborne heavy metals, and an elevated CHD risk. Further research is essential to validate and expand these findings, with the ultimate goal of enhancing public health outcomes.
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Contaminantes Atmosféricos , Bases de Datos Factuales , Cardiopatías Congénitas , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Embarazo , República de Corea/epidemiología , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/etiología , Cardiopatías Congénitas/inducido químicamente , Recién Nacido , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Efectos Tardíos de la Exposición Prenatal/epidemiología , Adulto , Exposición Materna/efectos adversos , Masculino , Dióxido de Azufre/análisis , Dióxido de Azufre/efectos adversos , Factores de Riesgo , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Programas Nacionales de Salud , Metales Pesados/efectos adversos , Metales Pesados/análisis , Metales Pesados/toxicidadRESUMEN
OBJECTIVE: To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD). METHODS: We conducted a systematic search for randomized controlled trials (RCTs) published through December 2022. The primary outcome was efficacy based on the incidence of POD (POD-I). Secondary outcomes included efficacy and safety according to the length of hospital or intensive care unit stay, in-hospital mortality, and adverse events. Subgroup analyses of POD-I were based on the type and dose of drug (low- and high-dose melatonin, ramelteon), the postoperative period (early or late), and the type of surgery. RESULTS: In the analysis (16 RCTs, 1981 patients), POD-I was lower in the treatment group than in the control group (risk ratio [RR] = 0.57). POD-I was lower in the high-dose melatonin group than in the control group (RR = 0.41), whereas no benefit was observed in the low-dose melatonin and ramelteon groups. POD-I was lower in the melatonin group in the early postoperative period (RR = 0.35) and in patients undergoing cardiopulmonary surgery (RR = 0.54). CONCLUSION: Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.
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Delirio , Melatonina , Complicaciones Posoperatorias , Melatonina/uso terapéutico , Melatonina/administración & dosificación , Melatonina/efectos adversos , Humanos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/tratamiento farmacológico , Delirio/prevención & control , Delirio/tratamiento farmacológico , Atención Perioperativa/métodos , Indenos/uso terapéutico , Indenos/efectos adversos , Indenos/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Tiempo de Internación , Resultado del Tratamiento , Mortalidad HospitalariaRESUMEN
Blood vessels permit the selective passage of molecules and immune cells between tissues and circulation. Uncontrolled inflammatory responses from an infection can increase vascular permeability and edema, which can occasionally lead to fatal organ failure. We identified mexenone as a vascular permeability blocker by testing 2,910 compounds in the Clinically Applied Compound Library using the lipopolysaccharide (LPS)-induced vascular permeability assay. Mexenone suppressed the LPS-induced downregulation of junctional proteins and phosphorylation of VE-cadherin in Bovine Aortic Endothelial Cells (BAECs). The injection of mexenone 1 hr before LPS administration completely blocked LPS-induced lung vascular permeability and acute lung injury in mice after 18hr. Our results suggest that mexenone-induced endothelial cell (EC) barrier stabilization could be effective in treating sepsis patients.
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Células Endoteliales , Lipopolisacáridos , Sepsis , Animales , Sepsis/tratamiento farmacológico , Sepsis/inducido químicamente , Sepsis/metabolismo , Ratones , Bovinos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Permeabilidad Capilar/efectos de los fármacos , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/prevención & control , Masculino , Cadherinas/metabolismo , Ratones Endogámicos C57BL , Antígenos CD/metabolismoRESUMEN
BACKGROUND: Paclitaxel is commonly used as a second-line therapy for advanced gastric cancer (AGC). The decision to proceed with second-line chemotherapy and select an appropriate regimen is critical for vulnerable patients with AGC progressing after first-line chemotherapy. However, no predictive biomarkers exist to identify patients with AGC who would benefit from paclitaxel-based chemotherapy. METHODS: This study included 288 patients with AGC receiving second-line paclitaxel-based chemotherapy between 2017 and 2022 as part of the K-MASTER project, a nationwide government-funded precision medicine initiative. The data included clinical (age [young-onset vs. others], sex, histology [intestinal vs. diffuse type], prior trastuzumab use, duration of first-line chemotherapy), and genomic factors (pathogenic or likely pathogenic variants). Data were randomly divided into training and validation sets (0.8:0.2). Four machine learning (ML) methods, namely random forest (RF), logistic regression (LR), artificial neural network (ANN), and ANN with genetic embedding (ANN with GE), were used to develop the prediction model and validated in the validation sets. RESULTS: The median patient age was 64 years (range 25-91), and 65.6% of those were male. A total of 288 patients were divided into the training (n = 230) and validation (n = 58) sets. No significant differences existed in baseline characteristics between the training and validation sets. In the training set, the areas under the ROC curves (AUROC) for predicting better progression-free survival (PFS) with paclitaxel-based chemotherapy were 0.499, 0.679, 0.618, and 0.732 in the RF, LR, ANN, and ANN with GE models, respectively. The ANN with the GE model that achieved the highest AUROC recorded accuracy, sensitivity, specificity, and F1-score performance of 0.458, 0.912, 0.724, and 0.579, respectively. In the validation set, the ANN with GE model predicted that paclitaxel-sensitive patients had significantly longer PFS (median PFS 7.59 vs. 2.07 months, P = 0.020) and overall survival (OS) (median OS 14.70 vs. 7.50 months, P = 0.008). The LR model predicted that paclitaxel-sensitive patients showed a trend for longer PFS (median PFS 6.48 vs. 2.33 months, P = 0.078) and OS (median OS 12.20 vs. 8.61 months, P = 0.099). CONCLUSIONS: These ML models, integrated with clinical and genomic factors, offer the possibility to help identify patients with AGC who may benefit from paclitaxel chemotherapy.
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Neoplasias Gástricas , Humanos , Masculino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Paclitaxel/uso terapéutico , Trastuzumab/uso terapéutico , Supervivencia sin Progresión , Genómica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse events in cancer patients and can negatively affect their quality of life (QoL). This study aimed to evaluate the clinical efficacy of an electric massage chair (EMC) for the treatment of CINV. METHODS: A randomized phase II cross-over trial was conducted on solid cancer patients who received moderate (MEC) to high emetogenic chemotherapy (HEC). The participants were randomly assigned to receive their first chemotherapy either on a standard bed (Group A) or in an EMC (Group B) during the infusion. The patients were then crossed over to the next cycle. CINV and QoL questionnaires were collected from the participants. RESULTS: A total of 59 patients completed the trial protocol and were included in the analysis, with 29 and 30 patients in Groups A and B, respectively. The mean INVR (Index of Nausea, Vomiting, and Retching) score in the 2nd day of the first cycle was higher in Group B (3.63 ± 5.35) than Group A (2.76 ± 4.78), but the difference was not statistically significant (p = 0.5367). The complete response rate showed little difference between the groups. Among the high-emetic risk subgroups, patients who received HEC (p = 0.04595), younger patients (p = 0.0108), and non-colorectal cancer patients (p = 0.0495) presented significantly lower CINV scores when EMC was applied. CONCLUSION: Overall, there was no significant difference in INVR scores between standard care and EMC. Applying EMC at the first chemotherapy infusion may help preserve QoL and reduce CINV in high-risk patients. TRIAL REGISTRATION: KCT0008200, 17/02/2023, Retrospectively registered.
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Antieméticos , Antineoplásicos , Neoplasias , Humanos , Calidad de Vida , Antieméticos/uso terapéutico , Antieméticos/efectos adversos , Estudios Cruzados , Vómitos/terapia , Vómitos/tratamiento farmacológico , Náusea/terapia , Náusea/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Antineoplásicos/efectos adversosRESUMEN
BACKGROUND: The question of whether dental procedures increase the risk of periprosthetic joint infection (PJI) in patients who have undergone total joint arthroplasty (TJA) remains controversial. QUESTIONS/PURPOSES: (1) Are dental procedures associated with an increased incidence of PJI in the setting of either primary or revision TKA after controlling for relevant potentially confounding variables? (2) Is the administration of prophylactic antibiotics before dental procedures associated with any differences in this risk? (3) Which factors are associated with increased incidence of PJI after dental procedures? METHODS: This nationwide, retrospective, comparative, large-database study evaluated 591,602 patients who underwent unilateral primary or revision TKA between 2009 and 2019 using the Health Insurance Review and Assessment Service data in South Korea, in which all people in South Korea were registered and to which all medical institutions must charge any procedures they performed. The study population was divided into 530,156 patients with dental procedures and 61,446 patients without dental procedures based on whether the patients underwent a dental procedure at least 1 year after the index surgery. After propensity score matching, patients were classified into a dental (n = 182,052) and a nondental cohort (n = 61,422). The dental cohort was then divided into two groups: 66,303 patients with prophylactic antibiotics and 115,749 patients without prophylactic antibiotics based on prophylactic antibiotic use. After propensity score matching, patients were categorized into prophylactic (n = 66,277) and nonprophylactic (n = 66,277) cohorts. Propensity score matching was used to control for covariates including posttraumatic arthritis associated with PJI risk according to the dental procedure and prophylactic antibiotic use among the cohorts. After propensity score matching, the standardized mean difference was confirmed to be less than 0.1 for all variables. Kaplan-Meier survival analyses, log-rank tests, and Cox proportional hazards regression analysis was performed. RESULTS: Dental procedures were not associated with an increase in PJI risk after primary (adjusted HR 1.56 [95% CI 0.30 to 8.15]; p = 0.60) or revision TKA (adjusted HR 1.74 [95% CI 0.90 to 3.34]; p = 0.10). Additionally, use of prophylactic antibiotics was not associated with a reduced PJI risk after the index surgery, either for primary (adjusted HR 1.28 [95% CI 0.30 to 5.42]; p = 0.74) or revision TKA (adjusted HR 0.74 [95% CI 0.45 to 1.23]; p = 0.25). Although surgery type and prophylactic antibiotic use exhibited no influence on PJI occurrence after dental procedures, posttraumatic arthritis was associated with PJI. The adjusted HR for posttraumatic arthritis was 4.54 (p = 0.046). CONCLUSION: Our findings suggest that dental procedures were not associated with an increased risk of PJI for up to 2 years after the dental procedure in patients who underwent either primary or revision TKA. Based on these findings, there is insufficient rationale for the use of prophylactic antibiotics before dental procedures in patients who have undergone primary or revision TKA. LEVEL OF EVIDENCE: Level III, therapeutic study.
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Artritis Infecciosa , Artroplastia de Reemplazo de Rodilla , Infecciones Relacionadas con Prótesis , Humanos , Antibacterianos/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Estudios Retrospectivos , Puntaje de Propensión , Infecciones Relacionadas con Prótesis/cirugía , Artritis Infecciosa/etiología , Odontología , Reoperación/efectos adversos , Factores de RiesgoRESUMEN
Abstract Background: Early identification of patients at risk of AKI after cardiac surgery is of critical importance for optimizing perioperative management and improving outcomes. This study aimed to identify the association between preoperative myoglobin levels and postoperative acute kidney injury (AKI) in patients undergoing valve surgery or coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass. Methods: This retrospective study included 293 patients aged over 17 years who underwent valve surgery or CABG with cardiopulmonary bypass. We excluded 87 patients as they met the exclusion criteria. Therefore, 206 patients were included in the final analysis. The patients' demographics as well as intraoperative and postoperative data were collected from electronic medical records. AKI was defined according to the Acute Kidney Injury Network classification system. Results: Of the 206 patients included in this study, 77 developed AKI. The patients who developed AKI were older, had a history of hypertension, underwent valve surgery with concomitant CABG, had lower preoperative hemoglobin levels, and experienced prolonged extracorporeal circulation (ECC) times. Multivariate logistic regression analysis revealed that preoperative myoglobin levels and ECC time were correlated with the development of AKI. A higher preoperative myoglobin level was an independent risk factor for the development of cardiac surgery-associated AKI. Conclusions: Higher preoperative myoglobin levels may enable physicians to identify patients at risk of developing AKI and optimize management accordingly.
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Humanos , Anciano , Lesión Renal Aguda/etiología , Lesión Renal Aguda/epidemiología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Puente Cardiopulmonar/efectos adversos , Factores de Riesgo , MioglobinaRESUMEN
High-level MET amplification (METamp) is a primary driver in â¼1%-2% of non-small cell lung cancers (NSCLCs). Cohort B of the phase 2 VISION trial evaluates tepotinib, an oral MET inhibitor, in patients with advanced NSCLC with high-level METamp who were enrolled by liquid biopsy. While the study was halted before the enrollment of the planned 60 patients, the results of 24 enrolled patients are presented here. The objective response rate (ORR) is 41.7% (95% confidence interval [CI], 22.1-63.4), and the median duration of response is 14.3 months (95% CI, 2.8-not estimable). In exploratory biomarker analyses, focal METamp, RB1 wild-type, MYC diploidy, low circulating tumor DNA (ctDNA) burden at baseline, and early molecular response are associated with better outcomes. Adverse events include edema (composite term; any grade: 58.3%; grade 3: 12.5%) and constipation (any grade: 41.7%; grade 3: 4.2%). Tepotinib provides antitumor activity in high-level METamp NSCLC (ClinicalTrials.gov: NCT02864992).
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Pirimidinas , Biopsia LíquidaRESUMEN
Air pollution is a risk factor that increases cardiovascular morbidity and mortality. In this study, we investigated the cardiotoxicity of particulate matter (PM) exposure using a zebrafish embryo model. We found that PM exposure induced cardiotoxicity, such as arrhythmia, during cardiac development. PM exposure caused cardiotoxicity by altering the expression levels of cardiac development (T-box transcription factor 20, natriuretic peptide A, and GATA-binding protein 4)- and ion-channel (scn5lab, kcnq1, kcnh2a/b, and kcnh6a/b)-related genes. In conclusion, this study showed that PM induces the aberrant expression of cardiac development- and ion channel-related genes, leading to arrhythmia-like cardiotoxicity in zebrafish embryos. Our study provides a foundation for further research on the molecular and genetic mechanisms of cardiotoxicity induced by PM exposure.
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Cardiotoxicidad , Pez Cebra , Animales , Pez Cebra/metabolismo , Cardiotoxicidad/genética , Cardiotoxicidad/metabolismo , Material Particulado/toxicidad , Material Particulado/metabolismo , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/genética , Arritmias Cardíacas/metabolismo , Canales Iónicos/genética , Corazón , Embrión no Mamífero/metabolismoRESUMEN
BACKGROUND: Poor dental health is correlated with an increased risk of cancer. Using a nationwide population cohort database, we investigated which cancer is highly associated with poor dental health and which dental indicator mostly influences cancer risk. METHODS: This study was conducted using the National Health Checkups (NHC) and National Health Insurance System (NHIS) database in Korea. NHC in Korea includes dental examinations. We retrieved subjects who underwent NHC between 2002 and 2003 and their medical information in NHIS database was followed until December 31,2015. RESULTS: Data for 200,170 who participated in the NHC between 2002 and 2003 were analysed. During the maximum follow-up period of 13 years, 15,506 (7.75%) subjects were diagnosed with cancer. The median time to cancer diagnosis after the dental examination was 87 months (range, 51-119 months). The proportion of people with missing teeth was higher in the cancer-diagnosed group than in the non-diagnosed group (26.27% vs. 22.59%, p < 0.001). Among several dental health factors, missing teeth were significantly associated with higher cancer risk. Subjects with missing teeth showed a 12% increased cancer risk compared to those without missing teeth (odds ratio [OR] 1.12, 95% confidence interval [CI], 1.08-1.16). The risk was significantly higher, especially in lung, head and neck, pancreatic, liver, biliary, and esophageal cancers (OR 1.27 [95% CI, 1.14-1.41], 1.32 [95% CI, 1.13-1.55], 1.27 [95% CI, 1.02-1.58], 1.24 [95% CI, 1.1-1.4], 1.28 [95% CI, 1.03-1.6], 1.4 [95% CI, 1.04-1.88], respectively). CONCLUSIONS: Missing teeth were the most important dental indicator associated with cancer risk. Korean adults with missing teeth should be cautious about the risk of several cancers, particularly head and neck, lung, gastrointestinal, hepatobiliary, and pancreatic cancer.
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Anodoncia , Neoplasias , Pérdida de Diente , Adulto , Humanos , Estudios de Cohortes , Pérdida de Diente/complicaciones , Pérdida de Diente/epidemiología , Neoplasias/epidemiología , República de Corea/epidemiologíaRESUMEN
The objective of this study was to evaluate the effects of high levels of maternal exposure to ambient air pollution and heavy metals on risks of autism spectrum disorder (ASD) and epilepsy using the National Health Insurance claims data of South Korea. The data of mothers and their newborns from 2016 to 2018 provided by the National Health Insurance Service were used (n = 843,134). Data on exposure to ambient air pollutants (PM2.5, CO, SO2, NO2, and O3) and heavy metals (Pb, Cd, Cr, Cu, Mn, Fe, Ni, and As) during pregnancy were matched based on the mother's National Health Insurance registration area. SO2 (OR: 2.723, 95% CI: 1.971-3.761) and Pb (OR: 1.063, 95% CI: 1.019-1.11) were more closely associated with the incidence of ASD when infants were exposed to them in the third trimester of pregnancy. Pb (OR: 1.109, 95% CI: 1.043-1.179) in the first trimester of pregnancy and Cd (OR: 2.193, 95% CI: 1.074-4.477) in the third trimester of pregnancy were associated with the incidence of epilepsy. Thus, exposure to SO2, NO2, and Pb during pregnancy could affect the development of a neurologic disorder based on the timing of exposure, suggesting a relationship with fetal development. However, further research is needed.
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Contaminantes Atmosféricos , Contaminación del Aire , Trastorno del Espectro Autista , Enfermedades del Sistema Nervioso , Embarazo , Lactante , Femenino , Humanos , Recién Nacido , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Exposición Materna/efectos adversos , Trastorno del Espectro Autista/etiología , Dióxido de Nitrógeno/efectos adversos , Dióxido de Nitrógeno/análisis , Cadmio , Plomo , Contaminación del Aire/efectos adversos , Material ParticuladoRESUMEN
BACKGROUND: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab. METHODS: This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75 mg/m2 ) and trastuzumab-pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR). RESULTS: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively. CONCLUSIONS: The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC. PLAIN LANGUAGE SUMMARY: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months.
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Neoplasias de la Mama , Carcinoma Ductal , Humanos , Femenino , Docetaxel/uso terapéutico , Micelas , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trastuzumab/uso terapéutico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Glándulas Salivales/metabolismo , Neoplasias de la Mama/tratamiento farmacológicoRESUMEN
Background and objectives: Herpes zoster (HZ) is caused by the reactivation of a pre-existing latent varicella zoster virus, which is one of the viruses that causes hearing loss, and hearing loss may occur due to a systemic immune response even if it does not invade the auditory nerve. This study aimed to determine the correlation between sudden sensorineural hearing loss (SSNHL) in older adult patients who received HZ treatment. Materials and Methods: We used the cohort data of patients aged 60 years and above (n = 624,646) between 2002 and 2015 provided by the National Health Insurance Service. The patients were divided into two groups: those who were diagnosed with HZ between 2003 and 2008 (group H, n = 36,121) and those who had not been diagnosed with HZ between 2002 and 2015 (group C, n = 584,329). Results: In the main model (adjusted HR = 0.890, 95% CI = 0.839-0.944, p < 0.001) adjusted for sex, age, and income, and the full model (adjusted HR = 0.894, 95% CI = 0.843-0.949, p < 0.001) adjusted for all comorbidities, group H had a lower risk of SSNHL than group C. Conclusions: This study showed that patients who received HZ treatment had a lower incidence of SSNHL within five years after diagnosis.
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Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Herpes Zóster , Humanos , Anciano , Herpesvirus Humano 3 , Modelos de Riesgos Proporcionales , Herpes Zóster/complicaciones , Herpes Zóster/tratamiento farmacológico , Herpes Zóster/epidemiología , Pérdida Auditiva Sensorineural/epidemiología , Pérdida Auditiva Súbita/tratamiento farmacológico , Pérdida Auditiva Súbita/epidemiología , República de Corea/epidemiología , Programas Nacionales de Salud , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: According to a recent meta-analysis, in patients with a body mass index (BMI) ≥ 30, a high fraction of inhaled oxygen (FiO2) did not increase postoperative atelectasis. However, a high FiO2 generally increases the risk of postoperative atelectasis. Therefore, this study aimed to evaluate the effect of FiO2 on the development of atelectasis in obese patients using the modified lung ultrasound score (LUSS). METHODS: Patients were assigned to 4 groups: BMI ≥ 30: group A (n = 21) and group B (n = 20) and normal BMI: group C (n = 22) and group D (n = 21). Groups A and C were administered 100% O2 during preinduction and emergence and 50% O2 during anesthesia. Groups B and D received 40% O2 for anesthesia. The modified LUSS was assessed before and 20 min after arrival to the postanesthesia care unit (PACU). RESULTS: The difference between the modified LUSS preinduction and PACU was significantly higher in group A with a BMI ≥ 30 (P = .006); however, there was an insignificant difference between groups C and D in the normal BMI group (P = .076). CONCLUSION: High FiO2 had a greater effect on the development of atelectasis in obese patients than did low FiO2; however, in normal-weight individuals, FiO2 did not have a significant effect on postoperative atelectasis.
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Pulmón , Atelectasia Pulmonar , Humanos , Estudios Prospectivos , Pulmón/diagnóstico por imagen , Atelectasia Pulmonar/diagnóstico por imagen , Atelectasia Pulmonar/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Obesidad/complicaciones , Obesidad/cirugía , OxígenoRESUMEN
Patients with peripheral arterial disease (PAD) are at a higher risk of developing postoperative complications. Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) plays an important role in atherosclerosis pathogenesis. In this study, the relationship between PAD and several single nucleotide polymorphisms (SNPs) of ALOX5AP (rs17216473, rs10507391, rs4769874, rs9551963, rs17222814, and rs7222842) was investigated in elderly patients undergoing general surgery. The medical records of 129 patients aged > 55 years who underwent elective general surgery between May 2018 and August 2019 were retrospectively reviewed. The A/A in rs17216473, A/A in rs10507391, G/G in rs4769874, and A/A in rs9551963 were calculated as 0 points and the rest as 1 point to define the genetic risk score. The prevalence of PAD tended to increase with higher genetic risk scores (patients had less ALOX5AP gene polymorphism of A/A in rs17216473, A/A in rs10507391, G/G in rs4769874, or A/A in rs9551963) (p = 0.005). Multivariate logistic regression analysis revealed that the genetic risk score (p = 0.009) and age (p = 0.007) were positively correlated with the prevalence of PAD. Genetic polymorphisms of ALOX5AP and age were associated with the prevalence of PAD in this study.
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Predisposición Genética a la Enfermedad , Enfermedad Arterial Periférica , Anciano , Humanos , Proteínas Activadoras de la 5-Lipooxigenasa/genética , Estudios Retrospectivos , Estudios de Casos y Controles , Enfermedad Arterial Periférica/epidemiología , Enfermedad Arterial Periférica/genética , Factores de Riesgo , Polimorfismo de Nucleótido SimpleRESUMEN
PURPOSE: BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants. MATERIALS AND METHODS: Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity. RESULTS: A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (VUS; gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w. CONCLUSION: We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.
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Neoplasias de la Mama , Neoplasias Ováricas , Femenino , Humanos , Biomarcadores de Tumor/genética , Proteína BRCA1/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Genes BRCA2 , Genómica , Mutación de Línea Germinal , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Neoplasias Ováricas/genéticaRESUMEN
BACKGROUND: Although various coronavirus disease 2019 (COVID-19) vaccines have been delivered to the public worldwide, data on cancer populations are limited. Vaccine hesitancy related to safety concerns is observed among cancer patients. We report the perception of COVID-19 vaccines and their safety profile after vaccination among cancer patients. MATERIALS AND METHODS: Between April and November 2021, a multicenter survey was conducted on 318 patients treated in any hemato-oncology outpatient clinic among three hospitals under the Korea University Medical Center. The medical records of the patients were reviewed to obtain detailed clinical and hematological toxicity data. RESULTS: A perception survey was conducted among 293 patients. Among them, 53.9% were concerned about developing vaccine-related adverse events (VRAEs) and 23.5%, about negative effects on cancer treatment. During the study period, 255 and 186 patients participated in a safety survey after the first and second doses, respectively. After the first dose, 62% of patients reported VRAEs (2.4%, grade 3), whereas 48.9% reported VRAEs (2.7%, grade 3) after the second dose. For both doses, injection-site pain and sore arm pain were the most common VRAEs, followed by myalgia, fatigue, and headache. No grade 4/5 VRAEs were observed, and there were no differences in complete blood count after vaccination. Multivariate analysis revealed female sex, active cancer treatment, and mRNA vaccines as independent risk factors for VRAE development in cancer patients. CONCLUSION: Despite high levels of concern, COVID-19 vaccines were well tolerated by cancer patients, with a safety profile consistent with that of the general population.