Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.400
Filtrar
Más filtros

Tipo del documento
Intervalo de año de publicación
1.
Proc Natl Acad Sci U S A ; 121(4): e2316477121, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38236737

RESUMEN

Ni is the second most abundant element in the Earth's core. Yet, its effects on the inner core's structure and formation process are usually disregarded because of its electronic and size similarity with Fe. Using ab initio molecular dynamics simulations, we find that the bcc phase can spontaneously crystallize in liquid Ni at temperatures above Fe's melting point at inner core pressures. The melting temperature of Ni is shown to be 700 to 800 K higher than that of Fe at 323 to 360 GPa. hcp, bcc, and liquid phase relations differ for Fe and Ni. Ni can be a bcc stabilizer for Fe at high temperatures and inner core pressures. A small amount of Ni can accelerate Fe's crystallization at core pressures. These results suggest that Ni may substantially impact the structure and formation process of the solid inner core.

2.
Proc Natl Acad Sci U S A ; 119(2)2022 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-34987099

RESUMEN

The Earth's inner core started forming when molten iron cooled below the melting point. However, the nucleation mechanism, which is a necessary step of crystallization, has not been well understood. Recent studies have found that it requires an unrealistic degree of undercooling to nucleate the stable, hexagonal, close-packed (hcp) phase of iron that is unlikely to be reached under core conditions and age. This contradiction is referred to as the inner core nucleation paradox. Using a persistent embryo method and molecular dynamics simulations, we demonstrate that the metastable, body-centered, cubic (bcc) phase of iron has a much higher nucleation rate than does the hcp phase under inner core conditions. Thus, the bcc nucleation is likely to be the first step of inner core formation, instead of direct nucleation of the hcp phase. This mechanism reduces the required undercooling of iron nucleation, which provides a key factor in solving the inner core nucleation paradox. The two-step nucleation scenario of the inner core also opens an avenue for understanding the structure and anisotropy of the present inner core.

3.
Proc Natl Acad Sci U S A ; 119(47): e2204485119, 2022 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-36375053

RESUMEN

Magnetic materials are essential for energy generation and information devices, and they play an important role in advanced technologies and green energy economies. Currently, the most widely used magnets contain rare earth (RE) elements. An outstanding challenge of notable scientific interest is the discovery and synthesis of novel magnetic materials without RE elements that meet the performance and cost goals for advanced electromagnetic devices. Here, we report our discovery and synthesis of an RE-free magnetic compound, Fe3CoB2, through an efficient feedback framework by integrating machine learning (ML), an adaptive genetic algorithm, first-principles calculations, and experimental synthesis. Magnetic measurements show that Fe3CoB2 exhibits a high magnetic anisotropy (K1 = 1.2 MJ/m3) and saturation magnetic polarization (Js = 1.39 T), which is suitable for RE-free permanent-magnet applications. Our ML-guided approach presents a promising paradigm for efficient materials design and discovery and can also be applied to the search for other functional materials.


Asunto(s)
Imanes , Metales de Tierras Raras , Retroalimentación , Magnetismo , Fenómenos Magnéticos , Aprendizaje Automático
4.
J Am Chem Soc ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38832750

RESUMEN

Dimerized quantum magnets are exotic crystalline materials where Bose-Einstein condensation of magnetic excitations can happen. However, known dimerized quantum magnets are limited to only a few oxides and halides. Here, we unveil 9 dimerized quantum magnets and 11 conventional antiferromagnets in ternary metal borides MTB4 (M = Sc, Y, La, Ce, Lu, Mg, Ca, and Al; T = V, Cr, Mn, Fe, Co, and Ni), where T atoms are arranged in structural dimers. Quantum magnetism in these compounds is dominated by strong antiferromagnetic (AFM) interactions between Cr (Cr and Mn for M = Mg and Ca) atoms within the dimers, with much weaker interactions between the dimers. These systems are proposed to be close to a quantum critical point between a disordered singlet spin-dimer phase, with a spin gap, and the ordered conventional Néel AFM phase. They greatly enrich the materials inventory that allows investigations of the spin-gap phase. Conventional antiferromagnetism in these compounds is dominated by ferromagnetic Mn (Fe for M = Mg and Ca) interactions within the dimers. The predicted stable and nonmagnetic (NM) YFeB4 phase is synthesized and characterized, providing a scarce candidate to study Fe dimers and Fe ladders in borides. The identified quantum, conventional, and NM systems provide a platform with abundant possibilities to tune the magnetic exchange coupling by doping and study the unconventional quantum phase transition and conventional magnetic transitions. This work opens new avenues for studying novel magnetism in borides arising from spin dimers and establishes a theoretical workflow for future searches for dimerized quantum magnets in other families of materials.

5.
Kidney Int ; 106(1): 35-49, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38705274

RESUMEN

Frailty is a condition that is frequently observed among patients undergoing dialysis. Frailty is characterized by a decline in both physiological state and cognitive state, leading to a combination of symptoms, such as weight loss, exhaustion, low physical activity level, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but also are at higher risk of hospitalization, infection, cardiovascular events, dialysis-associated complications, and death. Frailty occurs as a result of a combination and interaction of various medical issues in patients who are on dialysis. Unfortunately, frailty has no cure. To address frailty, a multifaceted approach is necessary, involving coordinated efforts from nephrologists, geriatricians, nurses, allied health practitioners, and family members. Strategies such as optimizing nutrition and chronic kidney disease-related complications, reducing polypharmacy by deprescription, personalizing dialysis prescription, and considering home-based or assisted dialysis may help slow the decline of physical function over time in subjects with frailty. This review discusses the underlying causes of frailty in patients on dialysis and examines the methods and difficulties involved in managing frailty among this group.


Asunto(s)
Fragilidad , Calidad de Vida , Diálisis Renal , Humanos , Fragilidad/diagnóstico , Fragilidad/epidemiología , Fragilidad/fisiopatología , Diálisis Renal/efectos adversos , Anciano , Anciano Frágil , Polifarmacia , Evaluación Geriátrica , Factores de Riesgo , Fallo Renal Crónico/terapia , Fallo Renal Crónico/fisiopatología , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/complicaciones
6.
Bioconjug Chem ; 35(5): 604-615, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38661725

RESUMEN

Chimeric antigen receptor T-cell (CAR-T cell) therapy has become a promising treatment option for B-cell hematological tumors. However, few optional target antigens and disease relapse due to loss of target antigens limit the broad clinical applicability of CAR-T cells. Here, we conjugated an antibody (Ab) fusion protein, consisting of an Ab domain and a SpyCatcher domain, with the FITC-SpyTag (FITC-ST) peptide to form a bispecific safety switch module using a site-specific conjugation system. We applied the safety switch module to target CD19, PDL1, or Her2-expressing tumor cells by constructing FMC63 (anti-CD19), antiPDL1, or ZHER (anti-Her2)-FITC-ST, respectively. Those switch modules significantly improved the cytotoxic effects of anti-FITC CAR-T cells on tumor cells. Additionally, we obtained the purified CD8+ T cells by optimizing a shorter version of the CD8-binding aptamer to generate anti-FITC CD8-CAR-T cells, which combined with the CD4-FITC-ST switch module (anti-CD4) to eliminate the CD4-positive tumor cells in vitro and in vivo. Overall, we established a novel safety switch module by site-specific conjugation to enhance the antitumor function of universal CAR-T cells, thereby expanding the application scope of CAR-T therapy and improving its safety and efficacy.


Asunto(s)
Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Humanos , Animales , Inmunoterapia Adoptiva/métodos , Ratones , Receptores Quiméricos de Antígenos/inmunología , Antígenos CD19/inmunología , Línea Celular Tumoral , Linfocitos T CD8-positivos/inmunología , Receptor ErbB-2/inmunología
7.
Osteoporos Int ; 35(4): 613-623, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38062161

RESUMEN

An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients. With further research, a treatment algorithm can be developed to potentially identify patients at high risk of preoperative mortality. INTRODUCTION: Red blood cell distribution width (RDW) is an independent predictor of various disease states in elderly individuals, but its association with the prognosis of elderly hip fracture patients is controversial. This study aimed to evaluate the prognostic value of RDW in such patients, construct a prediction model containing RDW using random survival forest (RSF) and Cox regression analysis, and compare RDW in patients with and without anemia. METHODS: We retrospectively analyzed the data of elderly patients who underwent hip fracture surgery, selected the best variables using RSF, stratified the independent variables by Cox regression analysis, constructed a 1-year mortality prediction model of elderly hip fracture with RDW, and conducted internal validation and external validation. RESULTS: Two thousand one hundred six patients were included in this study. The RSF algorithm selects 12 important influencing factors, and Cox regression analysis showed that eight variables including preoperative RDW (pre-RDW) were independent risk factors for death within 1-year after hip fracture surgery in elderly patients. Stratified analysis showed that pre-RDW was still independently associated with 1-year mortality in the non-anemia group and not in the anemia group. The nomogram prediction model had high differentiation and fit, and the prediction model constructed by the total cohort of patients was also used for validation of patients in the anemia patients and obtained good clinical benefits. CONCLUSION: An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients.


Asunto(s)
Anemia , Fracturas de Cadera , Humanos , Anciano , Índices de Eritrocitos , Estudios Retrospectivos , Oportunidad Relativa , Anemia/complicaciones , Pronóstico
8.
Dement Geriatr Cogn Disord ; 53(1): 29-36, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38316114

RESUMEN

INTRODUCTION: This study aimed to investigate the influence of case management and its corresponding computer-assisted assessment system on the quality improvement of dementia care. METHODS: This observational study enrolled 2029 patients and their caregivers at Changhua Christian Hospital in Taiwan. Physicians who made the diagnosis of dementia would introduce the patient and caregiver dyad to the case manager-centered collaborative care team after obtaining agreement. The achievement rates of 11 quality indicators (QIs) comprising timely diagnostic evaluations, regular screens of cognition and neuropsychiatric symptoms, caregiver support, and proper medication prescriptions were counted. Different timeframes (≤4 months, 4 months-1 year, 1-2 years, 2-3 years, or ≥3 years) from diagnosis of dementia to collaborative care intervention were compared. RESULTS: A significantly higher attainment rate was achieved for patients with earlier entry into the collaborative team model, including QIs about timely diagnosis and regular screening, and caregiver support. The QIs regarding dementia medication prescriptions and documentation of the risk of antipsychotics remained similar regardless of the time of entry into the model. The completion rates of QIs also improved after the information system was launched. CONCLUSIONS: Physician-case manager co-management in the setting of a collaborative care model with a computer-assisted assessment system helps improve QI achievement for dementia care.


Asunto(s)
Gestores de Casos , Demencia , Humanos , Demencia/diagnóstico , Demencia/terapia , Demencia/psicología , Indicadores de Calidad de la Atención de Salud , Atención Primaria de Salud , Cuidadores/psicología , Computadores
9.
Bioorg Med Chem Lett ; 109: 129822, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38823728

RESUMEN

The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.


Asunto(s)
Antibacterianos , Carbolinas , Bacterias Gramnegativas , Bacterias Grampositivas , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Carbolinas/farmacología , Carbolinas/química , Carbolinas/síntesis química , Humanos , Relación Estructura-Actividad , Animales , Ratones , Bacterias Grampositivas/efectos de los fármacos , Estructura Molecular , Bacterias Gramnegativas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Hep G2 , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos
10.
Inorg Chem ; 63(19): 8654-8663, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38682814

RESUMEN

A high-throughput screening using density functional calculations is performed to search for stable boride superconductors from the existing materials database. The workflow employs the fast frozen-phonon method as the descriptor to evaluate the superconducting properties quickly. Twenty-three stable candidates were identified during the screening. The superconductivity was obtained earlier experimentally or computationally for almost all found binary compounds. Previous studies on ternary borides are very limited. Our extensive search among ternary systems confirmed superconductivity in known systems and found several new compounds. Among these discovered superconducting ternary borides, TaMo2B2 shows the highest superconducting temperature of ∼12 K. Most predicted compounds were synthesized previously; therefore, our predictions can be examined experimentally. Our work also demonstrates that the boride systems can have diverse structural motifs that lead to superconductivity.

11.
Bioorg Med Chem ; 105: 117716, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38608329

RESUMEN

In this study, a series of new formylpiperazine-derived ferroptosis inhibitors were designed and synthesized based on the structure of a known ferroptosis inhibitor, ferrostatin-1 (Fer-1). The anti-ferroptosis activity of these synthetic compounds in human umbilical vein endothelial cells (HUVECs) induced by Erastin was evaluated. It was found that some of the new compounds, especially compound 26, showed potent anti-ferroptosis activity, as evidenced by its ability to restore cell viability, reduce iron accumulation, scavenge reactive oxygen species, maintain mitochondrial membrane potential, increase GSH levels, decrease LPO and MDA content, and upregulate GPX4 expression. Moreover, compound 26 exhibited superior microsomal stability than Fer-1. The present results suggest that compound 26 is a promising lead compound for the development of new ferroptosis inhibitors for the treatment of vascular diseases.


Asunto(s)
Supervivencia Celular , Ciclohexilaminas , Diseño de Fármacos , Ferroptosis , Células Endoteliales de la Vena Umbilical Humana , Piperazinas , Humanos , Ferroptosis/efectos de los fármacos , Piperazinas/farmacología , Piperazinas/síntesis química , Piperazinas/química , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Relación Estructura-Actividad , Ciclohexilaminas/farmacología , Ciclohexilaminas/química , Ciclohexilaminas/síntesis química , Supervivencia Celular/efectos de los fármacos , Estructura Molecular , Fenilendiaminas/farmacología , Fenilendiaminas/química , Fenilendiaminas/síntesis química , Relación Dosis-Respuesta a Droga , Especies Reactivas de Oxígeno/metabolismo , Compuestos Ferrosos/farmacología , Compuestos Ferrosos/química , Compuestos Ferrosos/síntesis química , Potencial de la Membrana Mitocondrial/efectos de los fármacos
12.
Phys Chem Chem Phys ; 26(12): 9510-9516, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38450725

RESUMEN

Ovonic threshold switching (OTS) selectors can effectively improve the storage density and suppress the leakage current of advanced phase-change memory devices. As a prototypical OTS material, amorphous GeSe is widely investigated. But the attention paid to amorphous Se (i.e., the functional constituent in amorphous GeSe) has been very limited up to now. Here we have explored the structure, bonding and electronic characteristics of amorphous Se using ab initio molecular dynamics simulations. The results reveal that the Se atoms in amorphous Se tend to form 2-coordinated configurations, and they connect with each other to form long chains. The fraction of the vibrational density of state located in the high frequency range is relatively large, and the formation energy of the Se-Se bond is as large as 4.44 eV, hinting that the Se-Se bonds in chains possess high stability. In addition, the mid-gap state related to the OTS behavior is also found in amorphous Se despite the small proportion. Our findings enrich the knowledge of amorphous Se, which aids the applications of Se-based OTS selectors.

13.
BMC Nephrol ; 25(1): 32, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38267859

RESUMEN

BACKGROUND: Diabetic kidney diseases (DKD) is a the most common cause of end-stage kidney disease (ESKD) around the world. Previous studies suggest that urinary podocyte stress biomarker, e.g. podocin:nephrin mRNA ratio, is a surrogate marker of podocyte injury in non-diabetic kidney diseases. METHOD: We studied 118 patients with biopsy-proved DKD and 13 non-diabetic controls. Their urinary mRNA levels of nephrin, podocin, and aquaporin-2 (AQP2) were quantified. Renal events, defined as death, dialysis, or 40% reduction in glomerular filtration rate, were determined at 12 months. RESULTS: Urinary podocin:nephrin mRNA ratio of DKD was significantly higher than the control group (p = 0.0019), while urinary nephrin:AQP2 or podocin:AQP2 ratios were not different between groups. In DKD, urinary podocin:nephrin mRNA ratio correlated with the severity of tubulointerstitial fibrosis (r = 0.254, p = 0.006). and was associated with the renal event-free survival in 12 months (unadjusted hazard ratio [HR], 1.523; 95% confidence interval [CI] 1.157-2.006; p = 0.003). After adjusting for clinical and pathological factors, urinary podocin:nephrin mRNA ratio have a trend to predict renal event-free survival (adjusted HR, 1.327; 95%CI 0.980-1.797; p = 0.067), but the result did not reach statistical significance. CONCLUSION: Urinary podocin:nephrin mRNA ratio has a marginal prognostic value in biopsy-proven DKD. Further validation is required for DKD patients without kidney biopsy.


Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Podocitos , Humanos , Nefropatías Diabéticas/diagnóstico , Pronóstico , Acuaporina 2/genética , Diálisis Renal , ARN Mensajero
14.
BMC Nephrol ; 25(1): 164, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745129

RESUMEN

BACKGROUND: Atypical haemolytic uremic syndrome (aHUS) is an uncommon form of thrombotic microangiopathy (TMA). However, it remains difficult to diagnose the disease early, given its non-specific and overlapping presentation to other conditions such as thrombotic thrombocytopenic purpura and typical HUS. It is also important to identify the underlying causes and to distinguish between primary (due to a genetic abnormality leading to a dysregulated alternative complement pathway) and secondary (often attributed by severe infection or inflammation) forms of the disease, as there is now effective treatment such as monoclonal antibodies against C5 for primary aHUS. However, primary aHUS with severe inflammation are often mistaken as a secondary HUS. We presented an unusual case of adult-onset Still's disease (AOSD) with macrophage activation syndrome (MAS), which is in fact associated with anti-complement factor H (anti-CFH) antibodies related aHUS. Although the aHUS may be triggered by the severe inflammation from the AOSD, the presence of anti-CFH antibodies suggests an underlying genetic defect in the alternative complement pathway, predisposing to primary aHUS. One should note that anti-CFH antibodies associated aHUS may not always associate with genetic predisposition to complement dysregulation and can be an autoimmune form of aHUS, highlighting the importance of genetic testing. CASE PRESENTATION: A 42 years old man was admitted with suspected adult-onset Still's disease. Intravenous methylprednisolone was started but patient was complicated with acute encephalopathy and low platelet. ADAMTS13 test returned to be normal and concurrent aHUS was eventually suspected, 26 days after the initial thrombocytopenia was presented. Plasma exchange was started and patient eventually had 2 doses of eculizumab after funding was approved. Concurrent tocilizumab was also used to treat the adult-onset Still's disease with MAS. The patient was eventually stabilised and long-term tocilizumab maintenance treatment was planned instead of eculizumab following haematology review. Although the aHUS may be a secondary event to MAS according to haematology opinion and the genetic test came back negative for the five major aHUS gene, high titre of anti-CFH antibodies was detected (1242 AU/ml). CONCLUSION: Our case highlighted the importance of prompt anti-CFH antibodies test and genetic testing for aHUS in patients with severe AOSD and features of TMA. Our case also emphasized testing for structural variants within the CFH and CFH-related proteins gene region, as part of the routine genetic analysis in patients with anti-CFH antibodies associated aHUS to improve diagnostic approaches.


Asunto(s)
Síndrome Hemolítico Urémico Atípico , Factor H de Complemento , Enfermedad de Still del Adulto , Humanos , Enfermedad de Still del Adulto/complicaciones , Enfermedad de Still del Adulto/diagnóstico , Enfermedad de Still del Adulto/tratamiento farmacológico , Síndrome Hemolítico Urémico Atípico/complicaciones , Síndrome Hemolítico Urémico Atípico/inmunología , Factor H de Complemento/inmunología , Adulto , Masculino , Autoanticuerpos/sangre , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/complicaciones , Síndrome de Activación Macrofágica/inmunología
15.
Heart Lung Circ ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38942623

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) is known to increase the risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE). However, the incidence, predictors, and outcomes of clinical thrombosis for inpatients with COVID-19 are not well known. This study aimed to enhance our understanding of clinical thrombosis in COVID-19, its associated factors, and mortality outcomes. METHOD: Hospitalised adult (≥18 years of age) patients with COVID-19 in 2020 were retrospectively identified from the US National Inpatient Sample database. Clinical characteristics, incident VTE, ATE, and in-hospital mortality outcomes were recorded. Multivariable logistic regression was performed to identify clinical factors associated with thrombosis and in-hospital mortality in COVID-19 inpatients. RESULTS: A total of 1,583,135 adult patients with COVID-19 in the year 2020 were identified from the National Inpatient Sample database; patients with thrombosis were 41% females with a mean age of 65.4 (65.1-65.6) years. The incidence of thrombosis was 6.1% (97,185), including VTE at 4.8% (76,125), ATE at 3.0% (47,790), and the in-hospital mortality rate was 13.4% (212,785). Patients with thrombosis were more likely to have respiratory symptoms of COVID-19 (76.7% vs 75%, p<0.001) compared with patients without thrombosis. The main factors associated with overall thrombosis, VTE, and ATE were paralysis, ventilation, solid tumours without metastasis, metastatic cancer, and acute liver failure. Although all thrombosis categories were associated with higher in-hospital mortality for COVID-19 inpatients in univariable analyses (p<0.001), they were not in multivariable analyses-thrombosis (odds ratio [OR] 1.24; 95% confidence interval [CI] 0.90-1.70; p=0.19), VTE (OR 0.70; 95% CI 0.52-1.00; p=0.05), and ATE (OR 1.07; 95% CI 0.92-1.25; p=0.36). CONCLUSIONS: The association of COVID-19 with thrombosis and VTE increases with increasing severity of the COVID-19 disease. Risk stratification of thrombosis is crucial in COVID-19 patients to determine the necessity of thromboprophylaxis.

16.
Clin Infect Dis ; 77(10): 1406-1412, 2023 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-37531093

RESUMEN

BACKGROUND: Nirmatrelvir-ritonavir is currently not recommended in patients with an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2. METHODS: To determine the safety profile and clinical and virological outcomes of nirmatrelvir-ritonavir use at a modified dosage in adults with chronic kidney disease (CKD), a prospective, single-arm, interventional trial recruited patients with eGFR <30 mL/minute/1.73 m2 and on dialysis. Primary outcomes included safety profile, adverse/serious adverse events, and events leading to drug discontinuation. Disease symptoms, virological outcomes by serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral polymerase chain reaction (PCR) tests, rapid antigen tests, and virological and symptomatic rebound were also recorded. RESULTS: Fifty-nine (69.4%) of the 85 participants had stage 5 CKD and were on dialysis. Eighty (94.1%) completed the full treatment course; 9.4% and 5.9% had adverse and serious adverse events, and these were comparable between those with eGFR < or >30 mL/minute/1.73 m2. The viral load significantly decreased on days 5, 15, and 30 (P < .001 for all), and the reduction was consistent in the subgroup with eGFR <30 mL/minute/1.73 m2. Ten patients had virological rebound, which was transient and asymptomatic. CONCLUSIONS: Among patients with CKD, a modified dose of nirmatrelvir-ritonavir is a well-tolerated therapy in mild COVID-19 as it can effectively suppress the SARS-CoV-2 viral load with a favorable safety profile. Virological and symptomatic rebound, although transient with low infectivity, may occur after treatment. Nirmatrelvir-ritonavir should be considered for use in patients with CKD, including stage 5 CKD on dialysis. Clinical Trials Registration. Clinical Trials.gov; identifier: NCT05624840.


Asunto(s)
COVID-19 , Fallo Renal Crónico , Lactamas , Leucina , Nitrilos , Prolina , Insuficiencia Renal Crónica , Adulto , Humanos , SARS-CoV-2 , Estudios Prospectivos , Ritonavir/efectos adversos , Tratamiento Farmacológico de COVID-19 , Insuficiencia Renal Crónica/complicaciones , Antivirales/efectos adversos
17.
Cancer Immunol Immunother ; 72(11): 3739-3753, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37707586

RESUMEN

CD19 CAR-T (chimeric antigen receptor-T) cell immunotherapy achieves a remission rate of approximately 70% in recurrent and refractory lymphoma treatment. However, the loss or reduction of CD19 antigen on the surface of lymphoma cells results in the escape of tumor cells from the immune killing of CD19 CAR-T cells (CAR19-T). Therefore, novel therapeutic strategies are urgently required. In this study, an anti-CD79b/CD3 bispecific antibody (BV28-OKT3) was constructed and combined with CAR19-T cells for B-cell lymphoma treatment. When the CD19 antigen was lost or reduced, BV28-OKT3 redirected CAR19-T cells to CD79b+ CD19- lymphoma cells; therefore, BV28-OKT3 overcomes the escape of CD79b+ CD19- lymphoma cells by the killing action of CAR19-T cells in vitro and in vivo. Furthermore, BV28-OKT3 triggered the antitumor function of CAR- T cells in the infusion product and boosted the antitumor immune response of bystander T cells, markedly improving the cytotoxicity of CAR19-T cells to lymphoma cells in vitro and in vivo. In addition, BV28-OKT3 elicited the cytotoxicity of donor-derived T cells toward lymphoma cells in vitro, which depended on the presence of tumor cells. Therefore, our findings provide a new clinical treatment strategy for recurrent and refractory B-cell lymphoma by combining CD79b/CD3 BsAb with CAR19-T cells.


Asunto(s)
Anticuerpos Biespecíficos , Linfoma de Células B , Linfoma , Humanos , Linfocitos T , Antígenos CD19 , Muromonab-CD3 , Linfoma/tratamiento farmacológico , Inmunoterapia Adoptiva/métodos
18.
Ann Surg Oncol ; 30(7): 4014-4025, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36566257

RESUMEN

BACKGROUND: Although the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing since the past decade, the proportion of AEG cases in two previous clinical trials (ACTS-GC and CLASSIC) that investigated the efficacy of adjuvant chemotherapy was relatively small. Therefore, whether AEG patients can benefit from adjuvant chemotherapy remains unclear. METHODS: Patients who were diagnosed with pathological stage II/III, Siewert II/III AEG, and underwent curative surgery at three high-volume institutions were assessed. Clinical outcomes were analyzed by using Kaplan-Meier curves, log-rank test, and Cox regression model. Propensity score matching (PSM) was used to reduce the selection bias. RESULTS: A total of 927 patients were included (the chemotherapy group: 696 patients; the surgery-only group: 231 patients). The median follow-up was 39.0 months. The 5-year overall survival was 63.1% (95% confidence interval [CI]: 59.0-67.6%) for the chemotherapy group and 50.2% in the surgery-only group (hazard ratio [HR] = 0.69, 95% CI: 0.54-0.88; p = 0.003). The 5-year, disease-free survival was 35.4% for the chemotherapy group and 16.6% for the surgery-only group (HR = 0.66, 95% CI: 0.53-0.83; p < 0.001). After PSM, the survival benefit of adjuvant chemotherapy for AEG was maintained. Multivariate analysis for overall survival and disease-free survival further demonstrated the survival benefit of adjuvant chemotherapy, with HRs of 0.63 (p < 0.001) and 0.52 (p < 0.001), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy was associated with improved overall survival and disease-free survival in patients with operable stage II or III AEG after D2 gastrectomy.


Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Humanos , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Unión Esofagogástrica/cirugía , Unión Esofagogástrica/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Gastrectomía , Quimioterapia Adyuvante
19.
J Cardiovasc Electrophysiol ; 34(3): 765-768, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36738138

RESUMEN

Guidelines recommend using the CHA2DS2-VASc score to determine anticoagulation decisions in atrial fibrillation (AF) patients, including those who undergo pulmonary vein isolation (PVI), however this may not consistently occur in the real-world setting because of other clinical factors. We sought to evaluate the anticoagulation prescription rates patterns in AF patients 1 year PVI at our institution. Consecutive AF patients undergoing PVI in our prospective registry during 2014-2018 who were alive at 1-year post-PVI were studied. Anticoagulation prescription rates at this time-point were adjudicated, and correlated to CHA2DS2-VASc score, sex, and heart rhythm status at 1 year. Amongst 4596 patients undergoing PVI, mean age was 64.2 ± 10.0 years, 1328 (28.9%) were female, and based on CHA2DS2-VASc score anticoagulation was not indicated, can be considered and indicated in 872 (19.0%), 1183 (25.7%), and 2541 (55.3%) patients, respectively. At 1-year after PVI, 3504 (76.2%) patients were on anticoagulation, and 792 (17.2%) had recurrence of AF. Anticoagulation was continued in over half of AF patients without classic CHA2DS2-VASc indication particularly in those with AF recurrence and women, while they were mildly under-prescribed in those with indication, especially for those without AF recurrence and men. In a large real world cohort of patients after PVI, anticoagulation prescription is not solely depending on the CHA2DS2-VASc score and sex, but also heart rhythm status and other clinical or imaging factors.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Fibrilación Atrial/cirugía , Venas Pulmonares/cirugía , Medición de Riesgo/métodos , Coagulación Sanguínea , Ablación por Catéter/métodos , Recurrencia , Resultado del Tratamiento
20.
Opt Express ; 31(19): 30239-30247, 2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37710570

RESUMEN

Quantum key distribution (QKD) promises unconditional security for communication. However, the random choices of the measurement basis in QKD usually result in low key creation efficiency. This drawback is overcome in the differential-phase-shift QKD, provided that each photon can be prepared in a large number of time slots with a proper waveform. In this work we develop a miniature room-temperature 1550-nm single-photon source to generate narrowband single photon in 50 time slots with a nearly optimal waveform for achieving unity key creation efficiency. By utilizing these single photons in the field test, we demonstrate the differential-phase-shift QKD with a key creation efficiency of 97%. Our work shows that the practical QKD can benefit from the narrowband single photons with controllable waveforms.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA