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Recurrent spillovers of α- and ß-coronaviruses (CoV) such as severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome-CoV, SARS-CoV-2, and possibly human CoV have caused serious morbidity and mortality worldwide. In this study, six receptor-binding domains (RBDs) derived from α- and ß-CoV that are considered to have originated from animals and cross-infected humans were linked to a heterotrimeric scaffold, proliferating cell nuclear antigen (PCNA) subunits, PCNA1, PCNA2, and PCNA3. They assemble to create a stable mosaic multivalent nanoparticle, 6RBD-np, displaying a ring-shaped disk with six protruding antigens, like jewels in a crown. Prime-boost immunizations with 6RBD-np in mice induced significantly high Ab titers against RBD antigens derived from α- and ß-CoV and increased interferon (IFN-γ) production, with full protection against the SARS-CoV-2 wild type and Delta challenges. The mosaic 6RBD-np has the potential to induce intergenus cross-reactivity and to be developed as a pan-CoV vaccine against future CoV spillovers.
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COVID-19 , Nanopartículas , Humanos , Animales , Ratones , SARS-CoV-2 , Anticuerpos Antivirales , COVID-19/prevención & control , Anticuerpos Neutralizantes , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
BACKGROUND: Ruling out obstructive coronary artery disease (CAD) using coronary computed tomography angiography (CCTA) is time-consuming and challenging. This study developed a deep learning (DL) model to assist in detecting obstructive CAD on CCTA to streamline workflows. METHODS: In total, 2929 DICOM files and 7945 labels were extracted from curved planar reformatted CCTA images. A modified Inception V3 model was adopted. To validate the artificial intelligence (AI) model, two cardiologists labelled and adjudicated the classification of coronary stenosis on CCTA. The model was trained to differentiate the coronary artery into binary stenosis classifications <50% and ≥50% stenosis. Using the quantitative coronary angiography (QCA) consensus results as a reference standard, the performance of the AI model and CCTA radiology readers was compared by calculating Cohen's kappa coefficients at patient and vessel levels. The net reclassification index was used to evaluate the net benefit of the DL model. RESULTS: The diagnostic accuracy of the AI model was 92.3% and 88.4% at the patient and vessel levels, respectively. Compared with CCTA radiology readers, the AI model had a better agreement for binary stenosis classification at both patient and vessel levels (Cohen kappa coefficient: .79 vs. .39 and .77 vs. .40, p < .0001). The AI model also exhibited significantly improved model discrimination and reclassification (Net reclassification index = .350; Z = 4.194; p < .001). CONCLUSIONS: The developed AI model identified obstructive CAD, and the model results correlated well with QCA results. Incorporating the model into the reporting system of CCTA may improve workflows.
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Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Humanos , Angiografía por Tomografía Computarizada/métodos , Constricción Patológica , Inteligencia Artificial , Valor Predictivo de las Pruebas , Estenosis Coronaria/diagnóstico por imagen , Angiografía Coronaria/métodosRESUMEN
Globally, women have been adopting oocyte cryopreservation (OC) for fertility preservation for various reasons, such as inevitable gonadotoxic treatment for specific pathologic states and social preferences. While conventional vitrification (C-VIT) has improved the success rate of OC, challenges of possible toxicities of high-concentration cryoprotective agents and osmotic stress persist. To overcome these challenges, we evaluated the ultra-fast vitrification (UF-VIT) method, which reduces the equilibration solution stage exposure time compared to C-VIT by observing mouse oocyte intracellular organelles and embryonic development. Consequently, compared to fresh mouse oocytes, UF-VIT presented significant differences only in endoplasmic reticulum (ER) intensity and mitochondrial (MT) distribution. Meanwhile, C-VIT showed substantial differences in the survival rate, key ER and MT parameters, and embryonic development rate. UF-VIT exhibited considerably fewer negative effects on key MT parameters and resulted in a notably higher blastocyst formation rate than C-VIT. Meiotic spindle (spindle and chromosomes) morphology showed no significant changes between the groups during vitrification/warming (VW), suggesting that VW did not negatively affect the meiotic spindle of the oocytes. In conclusion, UF-VIT seems more effective in OC owing to efficient cytoplasmic water molecule extraction, osmotic stress reduction, and minimization of cell contraction and expansion amplitude, thus compensating for the drawbacks of C-VIT.
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Crioprotectores , Vitrificación , Femenino , Animales , Ratones , Humanos , Crioprotectores/farmacología , Presión Osmótica , Criopreservación/métodos , OocitosRESUMEN
Youth violence remains a significant public health problem despite efforts to address it. We describe the evaluation results of Youth Empowerment Solutions (YES), an after-school active learning program implemented by trained local teachers and designed to engage middle school youth in multi-systematic promotive behaviors at the individual-, interpersonal-, and community-level to make lasting positive changes within the context of institutional disadvantages, such as racism. First, we used a modified randomized controlled trial design to examine the direct and indirect influence of YES on prosocial and delinquent behaviors 12 months after the conclusion of the program, through youth empowerment. Next, we evaluated these models by race, to determine if the intervention equitably promotes prosocial outcomes and decreases aggressive behaviors. Among 329 middle school students, YES participation enhanced prosocial behaviors through empowerment, and directly reduced aggressive behaviors a year after the conclusion of the program. This trend was particularly pronounced for African American youth. These effects were found after controlling for age, sex, and behavioral outcomes at baseline, and across different schools and teachers, suggesting that YES can also be sustainable and readily implemented by communities. The implications of the results for youth violence prevention, empowerment theory and intervention development and practice for ethnic minority youth who face structural disenfranchisement are discussed.
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Conducta del Adolescente , Altruismo , Adolescente , Agresión , Etnicidad , Humanos , Grupos Minoritarios , Violencia/prevención & controlRESUMEN
Chitinous fishery by-products have great application in the production of various bioactive compounds. In this study, Paenibacillus elgii TKU051, a protease-producing bacterial strain, was isolated using a medium containing 1% squid pens powder (SPP) as the sole carbon/nitrogen (C/N) source. P. elgii TKU051 was found to produce at least four proteases with molecular weights of 100 kDa, 57 kDa, 43 kDa, and 34 kDa (determined by the gelatin zymography method). A P. elgii TkU051 crude enzyme cocktail was optimally active at pH 6-7 and 60 °C. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and α-glucosidase inhibitory activity of the hydrolysates obtained from the hydrolysis of shrimp shell powder, shrimp head powder, shrimp meat powder, fish head powder and soya bean powder catalyzed by the P. elgii TkU051 crude enzyme cocktail were also evaluated. P. elgii TKU051 exhibited a high deproteinization capacity (over 94%) on different kinds of shrimp waste (shrimp heads and shells; fresh and cooked shrimp waste; shrimp waste dried by oven and lyophilizer), and the Fourier-transform infrared spectroscopy profile of the chitin obtained from the deproteinization process displayed the characteristic of chitin. Finally, the obtained chitin exhibited an effect comparable to commercial chitin in terms of adsorption against Congo Red (90.48% and 90.91%, respectively). Thus, P. elgii TKU051 showed potential in the reclamation of chitinous fishery by-products for proteases production and chitin extraction.
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Quitina/química , Explotaciones Pesqueras , Paenibacillus/metabolismo , Péptido Hidrolasas/biosíntesis , Residuos , Adsorción , Animales , Compuestos de Bifenilo/química , Colorantes/química , Rojo Congo/química , Decápodos , Decapodiformes , Fermentación , Picratos/química , Reciclaje , Contaminantes Químicos del Agua , alfa-Glucosidasas/metabolismoRESUMEN
BACKGROUND: Pheochromocytoma (PCC) has poor prognosis and adrenalectomy is hard to be performed, in case of caudal vena cava invasion. The long-term administration of phenoxybenzamine in PCC has not been reported in dogs. CASE PRESENTATION: A 14-year-old castrated male Poodle dog presented with an abdominal mass. On physical examination, hypertension, increased lens opacity, calcinosis cutis, generalized alopecia, and systolic murmur were observed. Serum chemistry and urinalysis profiles revealed hyperglycemia, hypercholesterolemia, elevated liver enzymes, and glucosuria. Abdominal ultrasonography showed a right adrenal mass with invasion of the caudal vena cava, which was cytologically diagnosed as suspected PCC. An adrenal mass (width × height × length, 28 × 26 × 48 mm3) was found on computed tomography and diagnosed as PCC with increased plasma metanephrines and normetanephrines. An adrenocorticotropin hormone stimulation test showed elevated adrenal hormones (androstenedione, estradiol, progesterone, and 17-OH progesterone) with normal cortisol, compatible with atypical Cushing's syndrome. The dog was managed with trilostane, phenoxybenzamine, and insulin therapy. Glycosylated hemoglobin and fructosamine levels gradually decreased, and hypertension resolved. In the 10-month follow-up period, the liver enzymes levels gradually decreased, and the clinical signs of the dog were well-controlled without deterioration. CONCLUSIONS: This case report describes long-term medical management without adrenalectomy of PCC complicated with atypical Cushing's syndrome and DM.
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Neoplasias de las Glándulas Suprarrenales/veterinaria , Enfermedades de los Perros/diagnóstico , Feocromocitoma/veterinaria , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Antagonistas Adrenérgicos alfa/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Síndrome de Cushing , Diabetes Mellitus/tratamiento farmacológico , Dihidrotestosterona/análogos & derivados , Dihidrotestosterona/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Fenoxibenzamina/uso terapéutico , Feocromocitoma/diagnóstico , Feocromocitoma/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: unplanned hospital admissions of older patients continue to attract the attention of UK policymakers, advisors and media. Reducing the number and length of stay (LOS) of these admissions has the potential to save NHS substantial costs while reducing iatrogenic risks. Some NHS trusts have introduced geriatric admission-avoidance systems, but evidence of their effectiveness is lacking. In September 2010, The Royal Free Hospital and Haverstock Healthcare Ltd, a GP provider organisation, introduced an admission-avoidance system for patients aged 70 or over: the Triage and Rapid Elderly Assessment Team (TREAT). OBJECTIVE: to measure the effect of TREAT on LOS and the rate of same-day discharges (an inverse measure of admission rate). SETTING: TREAT was based in the Accident and Emergency (A&E) department of the Royal Free Hospital, London. DESIGN: a pre- and post-retrospective cohort study comparing the 5,416 emergency geriatric admissions in the 12 months preceding the introduction of TREAT with the 5,370 emergency geriatric admissions in the 12 months following. Emergency geriatric admissions were divided into TREAT-matching and residual (non-matching) cohorts from hospital provider spell records, using the Healthcare Resource Group (HRG), treatment function and patient classification of the TREAT admissions. LOS and same-day discharge rates were measured over the pre- and post-TREAT periods: for the TREAT-matching cohort; for the residual cohort of emergency geriatric admissions; and for all emergency geriatric admissions. INTERVENTION: TREAT is a system of care combining early Accident and Emergency (A&E)-based senior doctor review, Comprehensive Geriatric Assessment (CGA), therapist assessment and supported discharge; post-discharge supported recovery; and a rapid access geriatric 'hot-clinic'. TREAT was supported by a post-acute care enablement (PACE) team, providing short-term nursing support immediately following discharge. RESULTS: TREAT accepted 593 geriatric admissions over a 12-month period, of which 32.04% were discharged on the day of admission. The mean LOS was 4.41 days, and the median LOS was 1 day. After the introduction of TREAT, mean LOS reduced by 18.16% (1.78 days, P < 0.001) for TREAT-matching admissions; by 11.65% (1.13 days, P < 0.001) for all emergency geriatric admissions; and by 1.08% (0.11 days, P = 0.065) for the residual population. Over the same period, the percentage of admissions resulting in same-day discharges increased from 12.26 to 16.23% (OR: 1.386, 95% CI: 1.203-1.597, P < 0.001) for TREAT-matching admissions, but for the residual population fell from 15.01 to 9.77% (OR: 0.613, P < 0.001, 95% CI: 0.737-0.509). CONCLUSIONS: TREAT appears to have reduced avoidable emergency geriatric admissions, and to have shortened LOS for all emergency geriatric admissions. It aims to address the King's Fund's call for an 'overall system of care rather than lots of discrete processes' through 'better design and co-ordination of services following the needs of older people'. The ease of set-up lends itself to replication and testing in clinical and cost-effectiveness studies. Further studies are needed to measure the impact of TREAT on re-admission rates, patient outcomes and satisfaction.
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Servicio de Urgencia en Hospital , Evaluación Geriátrica , Tiempo de Internación , Admisión del Paciente , Alta del Paciente , Triaje , Factores de Edad , Anciano , Envejecimiento , Prestación Integrada de Atención de Salud , Investigación sobre Servicios de Salud , Humanos , Londres , Oportunidad Relativa , Grupo de Atención al Paciente , Evaluación de Programas y Proyectos de Salud , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Although low-fluence 1,064-nm Q-switched Nd:YAG laser (QSNYL) is widely used for the treatment of melasma, multiple treatments are necessary for clinical improvement. Superficial chemical peeling using Jessner's solution has been used for treatment of melasma conventionally. OBJECTIVES: To evaluate the additional therapeutic effect and adverse effects of Jessner's peel when combined with 1,064 nm QSNYL for melasma patients in a double-blind, placebo-controlled design. METHODS: Total of 52 patients were included. Patients who received 10 sessions of 1,064 nm QSNYL plus chemical peeling with placebo (Group A) in a two-week intervals and those who received 10 sessions of 1,064 nm QSNYL plus chemical peeling with Jessner's solution (Group B) in a 2-week intervals were analyzed. Responses were evaluated using the Melasma Area and Severity Index (MASI) score, physician's global assessment (PGA) and subjective self-assessment. RESULTS: At 8 weeks, the mean MASI score decreased from 8.68 ± 4.06 to 8.60 ± 3.88 in Group A and from 8.98 ± 3.72 to 7.13 ± 2.57 in Group B, showing a significant difference (p < 0.001). But at 20 weeks, there was no significant difference on reduction of MASI, self-assessment, and PGA between the two groups. No serious adverse effects were reported with the additional Jessner's peeling. CONCLUSION: This study suggests Jessner's peel is a safe and effective method in the early course of treatment for melasma, when combined with low-fluence 1,064-nm QSNYL.
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Quimioexfoliación/métodos , Etanol/uso terapéutico , Ácido Láctico/uso terapéutico , Láseres de Estado Sólido/uso terapéutico , Terapia por Luz de Baja Intensidad/métodos , Melanosis/terapia , Resorcinoles/uso terapéutico , Salicilatos/uso terapéutico , Pueblo Asiatico , Terapia Combinada , Método Doble Ciego , Combinación de Medicamentos , Humanos , Satisfacción del PacienteRESUMEN
BACKGROUND: Given resource constraints during the coronavirus disease 2019 pandemic, we explored whether minimally invasive anatomic lung resections for early-stage lung cancer could undergo rapid discharge. METHODS: All patients with clinical stage I-II non-small cell lung cancer from September 2019 to June 2022 who underwent minimally invasive anatomic lung resection at a single institution were included. Patients discharged without a chest tube <18 hours after operation, meeting preset criteria, were considered rapid discharge. Demographics, comorbidities, operative details, and 30-day outcomes were compared between rapid discharge patients and nonrapid discharge "control" patients. Multivariable logistic regression was performed for predictors of nonrapid discharge. RESULTS: Overall, 430 patients underwent resection (200 lobectomies and 230 segmentectomies); 162 patients (37%) underwent rapid discharge and 268 patients (63%) were controls. The rapid discharge group was younger (66.5 vs 70.0 years; P < .001), was assigned to lower American Society of Anesthesiologists class (P = .02), had more segmentectomies than lobectomies (P = .003), and had smaller tumors (P < .001). There were no differences between groups in distance from home to hospital (P = .335) or readmission rates (P = .39). Increasing age had higher odds for nonrapid discharge (odds ratio, 1.04; 95% CI, 1.02-1.07), whereas segmentectomy had decreased odds (odds ratio, 0.46; 95% CI, 0.28-0.75). CONCLUSIONS: Approximately 37% of the patients underwent rapid discharge after operation with similar readmission rate to controls. Increasing age had higher odds for nonrapid discharge; segmentectomy was likely to lead to rapid discharge. Consideration of rapid discharge minimally invasive lung resection for early-stage lung cancer can result in significant reduction in inpatient resources without adverse patient outcomes.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/etiología , Alta del Paciente , Procedimientos Quirúrgicos Ambulatorios , Neumonectomía/efectos adversos , Pulmón/cirugía , Estudios RetrospectivosRESUMEN
AIMS: Patients with high-flow arteriovenous (AV) access are at risk of developing high-output cardiac failure (HOCF) and subsequent hospitalization. However, diagnosing HOCF is challenging and often requires invasive procedures. The role of systemic vascular resistance (SVR) in diagnosing HOCF is underestimated, and its predictive value is limited. Our study aims to identify non-invasive risk factors for HOCF to facilitate early diagnosis and timely surgical interventions. METHODS AND RESULTS: We included 109 patients with high-flow AV access who underwent serial echocardiography. The retrospective cohort was divided into two groups based on their hospitalization due to HOCF. The two groups were matched for age and gender. After a mean follow-up of 25.1 months, 19 patients (17.4%) were hospitalized due to HOCF. The two groups had similar baseline characteristics. However, the HOCF group had a higher value of vascular access blood flow (Qa) (2168 ± 856 vs. 1828 ± 617 mL/min; P = 0.045). Echocardiographic analysis revealed that the HOCF group had more pronounced left ventricular diastolic dysfunction (E/e': 21.1 ± 7.3 vs. 16.2 ± 5.9; P = 0.002), more severe pulmonary hypertension (right ventricular systolic pressure: 41.4 ± 16.7 vs. 32.2 ± 12.8; P = 0.009), a higher Doppler-derived cardiac index (CI) (4.3 ± 0.8 vs. 3.7 ± 1.1; P = 0.031), and a lower Doppler-derived estimated SVR (eSVR) value (5.5 ± 0.3 vs. 6.9 ± 0.2; P = 0.002) than the non-HOCF group. Using multivariable Cox regression analysis, a low eSVR value (<6) emerged as an independent predictor of HOCF hospitalization with a hazard ratio of 9.084 (95% confidence interval, 2.33-35.39; P = 0.001). Receiver operating characteristic curve analysis indicated that CI/eSVR values more accurately predicted HOCF hospitalization [sensitivity: 94.7%, specificity: 51.0%, area under the curve (AUC): 0.75, P < 0.001] than the Qa/cardiac output ratio (AUC: 0.50, P = 0.955), Qa values ≥ 2000 mL/min (AUC: 0.60, P = 0.181), and Qa values indexed for height in metres (AUC: 0.65, P = 0.040). CONCLUSIONS: In patients with high-flow AV access, low eSVR values obtained through non-invasive Doppler echocardiography were associated with a high rate of HOCF hospitalizations. Therefore, routine eSVR screening in these patients might expedite the diagnosis of HOCF.
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Insuficiencia Cardíaca , Humanos , Estudios Retrospectivos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Gasto Cardíaco , Resistencia Vascular , Ecocardiografía DopplerRESUMEN
BACKGROUND: It is unclear whether hydroxymethylglutaryl-CoA reductase inhibitor (statin) therapy decreases the risk of mortality and cardiovascular disease (CVD) in patients undergoing peritoneal dialysis (PD). METHODS: We performed a literature search of PubMed, Cochrane Library, Embase, and other databases for research publications up to June 2022. The outcomes of interest were fatal and nonfatal CVDs, all-cause mortality, and changes in the biochemical profiles. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled and synthesized using a random-effects model. The certainty of the evidence was determined using Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: Nine studies, including 2,933 patients undergoing PD, were included. Among them, three studies, including 2,099 patients, reported all-cause mortality, and three, including 1,571 patients, reported CVDs. In these patients, pooling results of two observational studies (very low-certainty evidence) showed that statin therapy significantly reduced CVDs (HR = 0.67; 95% CI = 0.54-0.84; p = 0.0004). Moreover, statin therapy was associated with significantly reduced low-density lipoprotein cholesterol, total cholesterol, and C-reactive protein levels (very low certainty of evidence). However, the effects of statin therapy on triglyceride, high-density lipoprotein, and albumin levels were not statistically significant. CONCLUSION: Although statin therapy was associated with significantly reduced low-density lipoprotein cholesterol, total cholesterol, and C-reactive protein levels, the probable beneficial effect of statins on CVD risk in patients undergoing PD could not be concluded firmly. Additional high-quality studies are required to assess the potential beneficial effects of statin therapy in PD patients.
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Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Diálisis Peritoneal , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Proteína C-Reactiva , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/tratamiento farmacológico , LDL-ColesterolRESUMEN
PURPOSE: Persistent levels of prostate-specific antigen (PSA) is a poor prognostic factor for recurrence after radical prostatectomy (RP). We investigated the impact of the percentage of residual PSA (%rPSA) [(post-/preoperative PSA)×100], representing a biochemical residual tumor, and the first postoperative PSA (fPSA) level on metastasis-free survival (MFS) in men with persistent levels of PSA after RP. MATERIALS AND METHODS: We retrospectively identified male patients within a single tertiary referral hospital database who harbored persistent (≥0.1 ng/mL) vs. undetectable (<0.1 ng/mL) PSA levels 4 to 8 weeks after RP. Kaplan-Meier analyses and Cox regression models were used to test the effect of persistent PSA levels, the fPSA level, and %rPSA on MFS. RESULTS: Of 1,205 patients, 178 patients with persistent PSA levels were enrolled. Seven-year MFS rates were 60.5% vs. 84.3% (p<0.001) for patients with a %rPSA ≥6% and <6%, respectively. Multivariable Cox regression models of the overall cohort revealed that persistent PSA levels (hazard ratio [HR], 3.94; p=0.010), extracapsular extension (HR, 4.17; 95% confidence interval [CI], 1.06-16.41; p=0.041), and pathological Gleason grade group (pGGG) (HR, 3.69; 95% CI, 1.32-10.27; p=0.013) were independent predictors of metastasis. Multivariable Cox regression models in men with persistent PSA levels revealed that the %rPSA (HR, 8.92; 95% CI, 1.74-45.71; p=0.009) and pGGG 4-5 (HR, 4.13; 95% CI, 1.22-13.96; p=0.022) were independent predictors of distant metastasis, but not the fPSA level after surgery. CONCLUSIONS: Persistent levels of PSA were associated with worse MFS after RP. In men with persistent PSA levels after RP, the %rPSA is a valuable predictor of MFS unlike the fPSA level.
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BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) have heterogeneous outcomes. As risk stratification mostly focuses on left-side myocardial function, we sought to investigate the prognostic value of right ventricular (RV) function in patients with HCM. METHODS: This retrospective cohort study included patients with HCM. Conventional ventricular functional parameters, including left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), and fractional area change were obtained. The longitudinal strain was analyzed using the speckle tracking method. The primary endpoint was defined as a composite of hospitalization for heart failure, sustained ventricular tachycardia, or all-cause death. RESULTS: A total of 56 patients with HCM (aged 58.0 ± 14.9 years, 64.3% male) were included. After a mean follow-up duration of 30.1 ± 17.4 months, primary endpoints developed in 10 (20%) of 50 patients who were treated medically. Patients with cardiovascular events had a more reduced LV thickest segmental strain, worse TAPSE, and more impaired RV free wall strain. After adjusting for age, sex, and LVEF, TAPSE (hazard ratio [HR], 95% confidence intervals [CIs]: 0.24, 0.06-0.93) and RV free wall strain (HR, 95% CIs:1.12, 1.03-1.21) remained independent prognostic predictors. Incorporating either TAPSE or RV free wall strain provides incremental prognostic value to the LV strain alone (net reclassification improvement by 31.4% and 34.1%, respectively, both p < 0.05). CONCLUSION: RV function assessed by TAPSE or RV free wall strain is predictive of subsequent cardiac events, suggesting that a comprehensive evaluation of RV function is useful for risk stratification in patients with HCM.
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Cardiomiopatía Hipertrófica , Función Ventricular Izquierda , Humanos , Masculino , Femenino , Estudios Retrospectivos , Volumen Sistólico , Medición de Riesgo , PronósticoRESUMEN
AIMS: The efficacy of catheter ablation (CA) on clinical outcomes and cardiac structural remodelling in atrial fibrillation (AF) patients with HF with mildly reduced or mid-range ejection fraction (HFmrEF) remains unclear. We aimed to compare the efficacy of CA with medical therapy (MT) in AF patients with HFmrEF. METHODS AND RESULTS: We retrospectively screened a total of 36 879 patients with AF between 2005 and 2020. Patients who were initially diagnosed with echocardiography-proved HFmrEF and had follow-up echocardiography were enrolled. After applying propensity score matching in a 1:1 ratio, 72 patients treated by CA (Group 1) and 72 patients receiving MT (Group 2) were taken into further analysis. The co-morbidities were similar between the two groups, except for hyperlipidaemia. After a mean follow-up duration of 58.9 ± 42.6 months, Group 1 had a lower HF hospitalization and all-cause mortality compared with Group 2 (hazard ratio (HR), 0.089 [95% confidence interval (CI), 0.011-0.747]; P = 0.026 and HR, 0.121 [95% CI, 0.016-0.894]; P = 0.038, respectively). As for cardiac structural remodelling, the Group 1 had a better improvement in left ventricular ejection fraction (LVEF) and a more decreased left atrium (LA) diameter than Group 2 (+25.0% ± 18.0% vs. +6.2% ± 21.6%, P = <0.0001 and -1.6 ± 4.7 mm vs. +1.5 ± 8.2 mm, P = 0.008, respectively). CONCLUSIONS: In patients with HFmrEF and AF, CA of AF could reduce both HF hospitalization and all-cause mortality as compared with those with MT. A significant improvement in LVEF and decrease in LA diameter were also observed in the CA group. Early rhythm control with CA should be taken into consideration in patients with HFmrEF and AF.
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Fibrilación Atrial , Insuficiencia Cardíaca , Humanos , Volumen Sistólico , Función Ventricular Izquierda , Estudios RetrospectivosRESUMEN
Noroviruses (NVs) are a major cause of foodborne diseases worldwide. The rhizomes of Acorus gramineus (AGR) have been used as a traditional medicinal plant and a food additive. In this study, AGR and its bioactive components-α-asarone and ß-asarone-showed significant antiviral activities against murine NV (MNV) with pre-treatment, with more than two log reductions in viral plaques. They also demonstrated strong inhibition on binding to A- and O-type saliva by the recombinant P domain derived from human NV (HuNV) GII.4. Both α- and ß-asarones also inhibited the binding of the P domain to the receptor at 0.125-1 mM in a concentration-dependent manner and induced a marked reduction in Tm, suggesting that they may reduce structural stability and block receptor binding by the P domain. In simulated digestive conditions, the AGR extract, α-asarone, or ß-asarone further showed a significant reduction of MNV plaques by 1.5-2.8 logs. The asarones show a potential for development as a scaffold for anti-NV agents.
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Acorus , Norovirus , Ratones , Humanos , Animales , Acorus/química , Rizoma/química , Antivirales/farmacología , Antivirales/análisis , Extractos Vegetales/farmacología , Extractos Vegetales/análisis , Aditivos Alimentarios/análisisRESUMEN
The clinical benefits of nootropics in the treatment of cognitive decline has been either limited or controversial. This study aimed to observe the effectiveness of cholinesterase inhibitor (ChEI) and nootropics combination in the treatment of cognitive impairment in dementia. Data were based on electronic medical records in a university health system. Patients with mild-to-moderate dementia and no history of prior cognitive enhancer use were included (n = 583). The subjects were categorized into the ChEI only group and the ChEI and nootropics combination group. The primary outcome measure was the change in cognitive function, as assessed by the mini-mental state examination (MMSE) from baseline to 300-400 days after the first ChEI prescription. Subsequent analyses were conducted in consideration of the dementia type, medical adherence, and type of nootropics. The changes in MMSE scores from baseline to endpoint were not significantly different between the two groups. In Alzheimer's dementia, the combination group showed significantly less deterioration in MMSE language subscale scores compared to the ChEI only group (F = 6.86, p = 0.009), and the difference was consistent in the highly adherent subjects (F = 10.16, p = 0.002). The choline alfoscerate and the ginkgo biloba extract subgroups in Alzheimer's dementia showed more significant improvements in the MMSE language subscale scores compared to the other nootropics subgroup (F = 7.04, p = 0.001). The present study showed that the effectiveness of ChEI and nootropics combination on cognition may appear differently according to the dementia type. This emphasizes the need for well-controlled studies to generalize the effectiveness of nootropics across various clinical settings.
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PURPOSE: This study aimed to validate the newly proposed risk model in Korean patients diagnosed with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A retrospective review was performed with 1,238 patients who underwent transurethral resection of bladder tumor from 2009 to 2020. We included 973 patients and categorized them into four risk groups according to the European Association of Urology (EAU) NMIBC risk stratification standards, which incorporate the World Health Organization 2004/2016 grading classification. Kaplan-Meyer survival analysis and multivariable analysis of time to progression were performed to calculate the probability of progression for all risk groups. RESULTS: A total of 973 patients were followed for 54.85 months. Patients were classified according to the risk factors proposed by the new NMIBC risk table and stratified into low, intermediate, high, and very high-risk groups based on the table. Cancer progression into muscle-invasive bladder cancer (MIBC) in each risk group was observed in 7 (4.4%), 24 (15.2%), 76 (48.1%), and 51 (32.3%) individuals, respectively. The progression rate was distinguishable between risk groups in the Kaplan-Meier progression-free survival analysis, and higher risk was associated with a higher rate of progression. The new NMIBC risk variables were demonstrated to have prognostic value in the multivariate analysis. The very high-risk group was associated with progression to muscle-invasive disease. CONCLUSIONS: This study demonstrates that the new EAU NMIBC risk group categorization is feasible in predicting the progression of NMIBC into MIBC in the Korean population and thus should be applied to clinical practice in Korea.
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Neoplasias de la Vejiga Urinaria , Urología , Humanos , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Klebsiella spp. is an important conditional pathogen in humans and animals. However, due to the indiscriminate use of antibiotics, the incidence of antimicrobial resistance has increased. OBJECTIVES: The purpose of this study was to investigate antimicrobial resistance in strains of Klebsiella strains and the phylogenetic relatedness of extended-spectrum cephalosporin (ESC)-resistance among Klebsiella strains isolated from clinically ill companion animals. METHODS: A total of 336 clinical specimens were collected from animal hospitals. Identification of Klebsiella species, determination of minimum inhibitory concentrations, detection of ESC resistance genes, polymerase chain reaction-based replicon typing of plasmids by conjugation, and multilocus sequence typing were performed. RESULTS: Forty-three Klebsiella strains were isolated and, subsequently, 28 were identified as K. pneumoniae, 11 as K. oxytoca, and 4 as K. aerogenes. Eleven strains were isolated from feces, followed by 10 from ear, 7 from the nasal cavity, 6 from urine, 5 from genitals, and 4 from skin. Klebsiella isolates showed more than 40% resistance to penicillin, cephalosporin, fluoroquinolone, and aminoglycoside. ESCresistance genes, CTX-M groups (CTX-M-3, CTX-M-15, and CTX-M-65), and AmpC (CMY-2 and DHA-1) were most common in the K. pneumoniae strains. Some K. pneumoniae carrying CTX-M or AmpC were transferred via IncFII plasmids. Two sequence types, ST709 and ST307, from K. pneumoniae were most common. CONCLUSIONS: In conclusion, this is the first report on the prevalence, ESCresistance genotypes, and sequence types of Klebsiella strains isolated from clinically ill companion animals. The combination of infectious diseases and antimicrobial resistance by Klebsiella in companion animals suggest that, in clinical veterinary, antibiotic selection should be made carefully and in conjunction with the disease diagnosis.
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Antibacterianos/farmacología , Enfermedades de los Gatos/epidemiología , Cefalosporinas/farmacología , Enfermedades de los Perros/epidemiología , Farmacorresistencia Bacteriana , Infecciones por Enterobacteriaceae/veterinaria , Klebsiella/efectos de los fármacos , Animales , Enfermedades de los Gatos/microbiología , Gatos , Enfermedades de los Perros/microbiología , Perros , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/microbiología , Klebsiella/aislamiento & purificación , Prevalencia , República de Corea/epidemiologíaRESUMEN
The use of radiopharmaceutical therapies (RPTs) in the treatment of cancers is growing rapidly, with more agents becoming available for clinical use in last few years and many new RPTs being in development. Dosimetry assessment is critical for personalized RPT, insofar as administered activity should be assessed and optimized in order to maximize tumor-absorbed dose while keeping normal organs within defined safe dosages. However, many current clinical RPTs do not require patient-specific dosimetry based on current Food and Drug Administration-labeled approvals, and overall, dosimetry for RPT in clinical practice and trials is highly varied and underutilized. Several factors impede rigorous use of dosimetry, as compared with the more convenient and less resource-intensive practice of empiric dosing. We review various approaches to applying dosimetry for the assessment of activity in RPT and key clinical trials, the extent of dosimetry use, the relative pros and cons of dosimetry-based versus fixed activity, and practical limiting factors pertaining to current clinical practice.
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Radiometría , Humanos , Dosificación RadioterapéuticaRESUMEN
Mixed results have been reported regarding whether habitual tea intake affects bone health. This study investigated the relationship between green tea intake and bone mineral density (BMD) in postmenopausal Korean women. We used data from the Korean National Health and Nutrition Examination Surveys from 2008 to 2011 and divided the participants into three groups according to their frequency of green tea intake over the past 12 months. BMD of the lumbar spine, total femur, and femur neck was measured using dual-energy X-ray absorptiometry. The odds ratios (ORs) and 95% confidence intervals (CIs) of osteoporosis and osteopenia according to green tea consumption were analyzed. Participants who did not consume green tea or consumed less than one cup per day were more likely to have osteopenia of the lumbar spine or femur than those who consumed it once to three times a day (OR 1.81 and 1.85, 95% CI, 1.20-2.71; and 1.23-2.77). Moreover, ORs for osteoporosis were 1.91 (95% CI 1.13-3.23) and 1.82 (95% CI 1.09-3.05) in non-consumers and consumers who drank less than one cup per day, respectively, compared with the reference group. These results support that green tea consumption may have benefits on bone health.