Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
1.
Exp Clin Transplant ; 22(3): 239-241, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38695593

RESUMEN

Encapsulating peritoneal sclerosis is a rare but highly morbid disease process in patients with end-stage kidney disease on peritoneal dialysis. Surgical management has been described in patients with encapsulation of bowel causing obstruction. Here, we describe a case of surgical management in a patient following kidney transplant with medically refractory ascites and lower extremity edema.


Asunto(s)
Fallo Renal Crónico , Trasplante de Riñón , Fibrosis Peritoneal , Humanos , Trasplante de Riñón/efectos adversos , Fibrosis Peritoneal/cirugía , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/diagnóstico , Fibrosis Peritoneal/diagnóstico por imagen , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/diagnóstico , Resultado del Tratamiento , Ascitis/etiología , Ascitis/cirugía , Ascitis/diagnóstico , Edema/etiología , Edema/cirugía , Masculino , Diálisis Peritoneal/efectos adversos , Femenino , Persona de Mediana Edad , Adulto
2.
Exp Hematol ; 129: 104125, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38743005

RESUMEN

The revised International Prognostic Index (R-IPI) is an important prognostic tool in diffuse large B cell lymphoma (DLBCL); however, outcomes can vary markedly within R-IPI groups, and additional prognostic markers are needed. We conducted a prospective observational study to evaluate the circulating immature myeloid (IM) cell subsets and cytokine profiles of 31 patients with newly diagnosed DLBCL before and after chemoimmunotherapy. Among circulating IM cells, myeloid-derived suppressor cells (MDSCs) were the predominant cell type (73.8% ± 26%). At baseline, circulating monocytic MDSCs (M-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) were predominantly mutually exclusive. Patients with DLBCL clustered into three distinct immunotypes according to MDSC levels and subtype predominance: M-MDSChigh, PMN-MDSChigh, and MDSClow. The M-MDSChigh immunotype was associated with the germinal center B cell-like (GCB) subtype and elevated serum IL-8 and MIP-1α levels. PMN-MDSChigh was associated with the non-GCB subtype and elevated IL-8, MCP-1, IP-10, TNFα, and IL-1Ra levels. Standard chemoimmunotherapy partially reduced M-MDSC distribution across the MDSClow and M-MDSChigh groups. By contrast, among the MDSClow and PMN-MDSChigh groups, PMN-MDSCs persisted after treatment. Two high-risk patients with non-GCB DLBCL and MDSClow immunotype experienced early disease recurrence within 12 months of treatment completion. This study demonstrates that distinct types of MDSCs are associated with subtypes of DLBCL. MDSC levels are dynamic and may be associated with disease status. Persistence of PMN-MDSCs among high-risk patients with DLBCL may be associated with early relapse.


Asunto(s)
Linfoma de Células B Grandes Difuso , Células Supresoras de Origen Mieloide , Humanos , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/patología , Células Supresoras de Origen Mieloide/metabolismo , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/sangre , Femenino , Masculino , Persona de Mediana Edad , Anciano , Pronóstico , Inflamación/patología , Adulto , Estudios Prospectivos , Anciano de 80 o más Años , Citocinas/sangre , Inmunoterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
4.
Future Oncol ; 20(1): 39-53, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37476983

RESUMEN

Aim: To investigate real-world time to next treatment in patients with chronic lymphocytic leukemia initiating first-line (1L) ibrutinib or acalabrutinib. Materials & methods: US specialty pharmacy electronic medical records (21/11/2018-30/4/2022) were used; patients initiated 1L on/after 21/11/2019 (acalabrutinib approval). Results: Among 710 patients receiving ibrutinib, 5.9% initiated next treatment (mean time to initiation = 9.2 months); among 373 patients receiving acalabrutinib, 7.5% initiated next treatment (mean time to initiation = 5.9 months). Adjusting for baseline characteristics, acalabrutinib-treated patients were 89% more likely to initiate next treatment (hazard ratio = 1.89; p = 0.016). Conclusion: This study addresses a need for real-world comparative effectiveness between 1L ibrutinib and acalabrutinib and shows that next treatment (a clinically meaningful measure for real-world progression) occurred less frequently with 1L ibrutinib.


Ibrutinib and acalabrutinib are oral medications taken once-daily and twice-daily, respectively. They are recommended as initial treatment for chronic lymphocytic leukemia (CLL). The goal of this study was to compare the efficacy of these treatments as initial treatment for CLL. To meet this goal, real-world US specialty pharmacy electronic medical records between 11/21/2018­4/30/2022 were used. Patients treated with ibrutinib or acalabrutinib as initial treatment for CLL were studied. Treatment had to be started on or after the date of acalabrutinib approval for CLL (11/21/2019). Time to next treatment was used to estimate real-world disease progression. It was defined as the time from the initiation of initial treatment with ibrutinib or acalabrutinib to the initiation of a next treatment. Study results showed that patients were observed for a median of up to 1.5 years. Over this period, next treatment was more likely for acalabrutinib (7.5%) compared with ibrutinib (5.9%). After adjusting for differences in patient characteristics, next treatment was 89% more likely with acalabrutinib than ibrutinib. This study addresses a need to compare the effectiveness of initial treatment with ibrutinib and acalabrutinib in the real-world. It helps better contextualize results from clinical trial data and shows that next treatment occurred less frequently with ibrutinib.


Asunto(s)
Adenina/análogos & derivados , Leucemia Linfocítica Crónica de Células B , Pirazinas , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Piperidinas , Benzamidas/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos
5.
Microsc Microanal ; 29(6): 2026-2036, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38066670

RESUMEN

Electron counting can be performed algorithmically for monolithic active pixel sensor direct electron detectors to eliminate readout noise and Landau noise arising from the variability in the amount of deposited energy for each electron. Errors in existing counting algorithms include mistakenly counting a multielectron strike as a single electron event, and inaccurately locating the incident position of the electron due to lateral spread of deposited energy and dark noise. Here, we report a supervised deep learning (DL) approach based on Faster region-based convolutional neural network (R-CNN) to recognize single electron events at varying electron doses and voltages. The DL approach shows high accuracy according to the near-ideal modulation transfer function (MTF) and detector quantum efficiency for sparse images. It predicts, on average, 0.47 pixel deviation from the incident positions for 200 kV electrons versus 0.59 pixel using the conventional counting method. The DL approach also shows better robustness against coincidence loss as the electron dose increases, maintaining the MTF at half Nyquist frequency above 0.83 as the electron density increases to 0.06 e-/pixel. Thus, the DL model extends the advantages of counting analysis to higher dose rates than conventional methods.

6.
Clin Cancer Res ; 29(23): 4941-4948, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37738027

RESUMEN

PURPOSE: Patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib are at risk of developing cardiovascular side effects (CVSE). The molecular determinants of CVSEs have not been fully elucidated. We interrogated genetic polymorphisms in the Bruton tyrosine kinase (BTK) signaling pathway for their association with ibrutinib-related CVSEs. EXPERIMENTAL DESIGN: We conducted a retrospective/prospective observational pharmacogenetic study of 50 patients with newly diagnosed or relapsed CLL who received ibrutinib at a starting daily dose of 420 mg for at least 6 months. CVSEs, primarily atrial fibrillation and hypertension, occurred in 10 patients (20%), of whom 4 discontinued therapy. DNA was isolated from buccal swabs of all 50 patients and genotyped for 40 SNPs in GATA4, SGK1, KCNQ1, KCNA4, NPPA, and SCN5A using a customized next-generation sequencing panel. Univariate and multivariate logistic regression analysis were performed to determine genetic and clinical factors associated with the incidence of ibrutinib-related CVSEs. RESULTS: GATA4 rs804280 AA (P = 0.043), KCNQ1 rs163182 GG (P = 0.036), and KCNQ1 rs2237895 AA (P = 0.023) genotypes were univariately associated with ibrutinib-related CVSEs. On the basis of multivariate analysis, a high genetic risk score, defined as the presence of at least two of these genotypes, was associated with 11.5-fold increased odds of CVSEs (P = 0.019; 95% confidence interval, 1.79-119.73). CONCLUSIONS: Our findings suggest possible genetic determinants of ibrutinib-related CVSEs in CLL. If replicated in a larger study, pretreatment pharmacogenetic testing for GATA4 and KCNQ1 polymorphisms may be a useful clinical tool for personalizing treatment selection for CLL and/or instituting early risk mitigation strategies.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Estudios Retrospectivos , Canal de Potasio KCNQ1 , Piperidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico
8.
Patient Prefer Adherence ; 17: 2073-2084, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37641660

RESUMEN

Purpose: Increased dosing frequency adversely affects treatment adherence and outcomes in chronic diseases; however, such data related to treatment adherence is lacking in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). This study compared adherence between patients treated with ibrutinib (once-daily) versus acalabrutinib (twice-daily) as first-line (1L) therapy for CLL/SLL. Patients and Methods: Specialty pharmacy electronic medical records were used to identify adults with CLL/SLL initiating 1L ibrutinib or acalabrutinib between 01/01/2018 and 11/30/2020. Adherence was measured by the proportion of days covered (PDC) and medication possession ratio (MPR) and was compared between cohorts using odds ratios (ORs) obtained from logistic regression models adjusted for baseline characteristics. Results: Between 01/01/2018 and 11/30/2020, 1374 and 140 patients initiated ibrutinib and acalabrutinib, respectively. Based on PDC/MPR ≥80%, patients treated with once-daily ibrutinib were more likely to be adherent than those treated with twice-daily acalabrutinib (OR ranges: PDC: 1.04-1.76; MPR: 1.03-1.58). At 6 months, patients on ibrutinib had a 58-76% higher likelihood of staying adherent compared to patients on acalabrutinib (PDC: 75.9% for ibrutinib vs 63.6% for acalabrutinib, OR: 1.76, P=0.008; MPR: 76.8% vs 66.9%, OR: 1.58, P=0.036) with a similar trend noted for the entire line of treatment (LOT) (PDC: 53.0% vs 41.4%, OR: 1.53, P=0.021; MPR: 58.7% vs 47.1%, OR: 1.50, P=0.027). Conclusion: In this real-world analysis, CLL/SLL patients initiating 1L once-daily ibrutinib had >50% higher treatment adherence than those initiating twice-daily acalabrutinib during their LOT. Given the importance of sustained adherence for disease control in CLL/SLL, dosing frequency may be an important consideration for patients and physicians.

9.
Clin Cancer Res ; 29(14): 2593-2601, 2023 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-37282671

RESUMEN

PURPOSE: The CAPTIVATE study investigated first-line ibrutinib plus venetoclax for chronic lymphocytic leukemia in 2 cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). We report outcomes of fixed-duration ibrutinib plus venetoclax in patients with high-risk genomic features [del(17p), TP53 mutation, and/or unmutated immunoglobulin heavy chain (IGHV)] in CAPTIVATE. PATIENTS AND METHODS: Patients received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day). FD cohort patients (n = 159) received no further treatment. Forty-three MRD cohort patients with confirmed undetectable MRD (uMRD) after 12 cycles of ibrutinib plus venetoclax received randomized placebo treatment. RESULTS: Of 195 patients with known status of genomic risk features at baseline, 129 (66%) had ≥1 high-risk feature. Overall response rates were >95% regardless of high-risk features. In patients with and without high-risk features, respectively, complete response (CR) rates were 61% and 53%; best uMRD rates: 88% and 70% (peripheral blood) and 72% and 61% (bone marrow); 36-month progression-free survival (PFS) rates: 88% and 92%. In subsets with del(17p)/TP53 mutation (n = 29) and unmutated IGHV without del(17p)/TP53 mutation (n = 100), respectively, CR rates were 52% and 64%; uMRD rates: 83% and 90% (peripheral blood) and 45% and 80% (bone marrow); 36-month PFS rates: 81% and 90%. Thirty-six-month overall survival (OS) rates were >95% regardless of high-risk features. CONCLUSIONS: Deep, durable responses and sustained PFS seen with fixed-duration ibrutinib plus venetoclax are maintained in patients with high-risk genomic features, with similar PFS and OS to those without high-risk features. See related commentary by Rogers, p. 2561.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/mortalidad , Piperidinas/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico
10.
Sci Rep ; 13(1): 5178, 2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-36997628

RESUMEN

Accurately quantifying swelling of alloys that have undergone irradiation is essential for understanding alloy performance in a nuclear reactor and critical for the safe and reliable operation of reactor facilities. However, typical practice is for radiation-induced defects in electron microscopy images of alloys to be manually quantified by domain-expert researchers. Here, we employ an end-to-end deep learning approach using the Mask Regional Convolutional Neural Network (Mask R-CNN) model to detect and quantify nanoscale cavities in irradiated alloys. We have assembled a database of labeled cavity images which includes 400 images, > 34 k discrete cavities, and numerous alloy compositions and irradiation conditions. We have evaluated both statistical (precision, recall, and F1 scores) and materials property-centric (cavity size, density, and swelling) metrics of model performance, and performed targeted analysis of materials swelling assessments. We find our model gives assessments of material swelling with an average (standard deviation) swelling mean absolute error based on random leave-out cross-validation of 0.30 (0.03) percent swelling. This result demonstrates our approach can accurately provide swelling metrics on a per-image and per-condition basis, which can provide helpful insight into material design (e.g., alloy refinement) and impact of service conditions (e.g., temperature, irradiation dose) on swelling. Finally, we find there are cases of test images with poor statistical metrics, but small errors in swelling, pointing to the need for moving beyond traditional classification-based metrics to evaluate object detection models in the context of materials domain applications.

11.
Haematologica ; 108(1): 98-109, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-35833303

RESUMEN

Allogeneic hematopoietic cell transplantation (alloHCT) can potentially salvage large B-cell lymphoma (LBCL) patients experiencing treatment failure after chimeric antigen receptor T-cell therapy (CAR T). Nonetheless, data on the efficacy and toxicities of alloHCT after receipt of CAR T are limited. We report a multicenter retrospective study assessing the safety, toxicities, and outcomes of alloHCT in LBCL patients following CAR T failure. Eighty-eight patients with relapsed, refractory LBCL received an alloHCT following anti-CD19 CAR T failure. The median number of lines of therapy between CAR T infusion and alloHCT was one (range, 0-7). Low intensity conditioning was used in 77% (n=68) and peripheral blood was the most common graft source (86%, n=76). The most common donor types were matched unrelated donor (39%), followed by haploidentical (30%) and matched related donor (26%). Median follow-up of survivors was 15 months (range, 1-72). One-year overall survival, progression-free survival, and graft-versus-host disease-free relapse-free survival were 59%, 45%, and 39% respectively. One-year non-relapse mortality and progression/relapse were 22% and 33% respectively. On multivariate analysis, <2 lines of intervening therapy between CAR T and alloHCT and complete response at time of alloHCT were associated with better outcomes. In conclusion, alloHCT after CAR T failure can provide durable remissions in a subset of patients.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Humanos , Inmunoterapia Adoptiva/efectos adversos , Estudios Retrospectivos , Recurrencia Local de Neoplasia/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/etiología , Trasplante Homólogo , Antígenos CD19
12.
J Thorac Cardiovasc Surg ; 165(1): 351-363.e20, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36088143

RESUMEN

OBJECTIVE: Segmentectomy has become an accepted procedure for the treatment of non-small cell lung cancer. Adequate lymph node sampling, sufficient margins, and proper tumor size selection are factors vital for achieving outcomes comparable to lobectomy. Previous studies have demonstrated poor adherence to lymph node sampling guidelines. However, national trends in the quality of segmentectomy and implications on survival are unknown. METHODS: The National Cancer Database was used to identify patients with clinical stage I to IIA non-small cell lung cancer surgically treated between 2004 and 2018. Facility-level trends in extent of resection and segmentectomy odds of adherence to (1) 2014 Commission on Cancer guidelines of sampling 10 or more lymph nodes, (2) negative (R0) resection margins, and (3) tumor size 2 cm or less were determined. Propensity score matching was based on segmentectomy adherence to (4) a composite of all measures, and survival was evaluated with Cox models and Kaplan-Meier survival estimates. RESULTS: The study included 249,391 patients with 4.4% (n = 11,006) treated with segmentectomy. The proportion of segmentectomies performed annually increased from 3.3% in 2004 to 6.1% in 2018 (P < .001). Overall, 12.6% (n = 1385) of patients who underwent segmentectomy between 2004 and 2018 were adherent to all measures, and adherence was more likely at academic programs (odds ratio, 1.56; 95% confidence interval, 1.14-2.15) than nonacademic programs (P < .001, reference). Adherence to all measures was associated with improved survival (hazard ratio, 0.67; 95% confidence interval, 0.56-0.79). CONCLUSIONS: As segmentectomy is increasingly established as a valid oncological option for the treatment of non-small cell lung cancer, it is important that quality remains high. This study demonstrates that continued improvement is needed.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Neumonectomía/métodos , Mastectomía Segmentaria , Estadificación de Neoplasias , Resultado del Tratamiento , Estudios Retrospectivos
13.
Clin Cancer Res ; 28(20): 4385-4391, 2022 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-35939599

RESUMEN

PURPOSE: The phase II CAPTIVATE study investigated first-line treatment with ibrutinib plus venetoclax for chronic lymphocytic leukemia in two cohorts: minimal residual disease (MRD)-guided randomized treatment discontinuation (MRD cohort) and fixed duration (FD cohort). We report tumor debulking and tumor lysis syndrome (TLS) risk category reduction with three cycles of single-agent ibrutinib lead-in before initiation of venetoclax using pooled data from the MRD and FD cohorts. PATIENTS AND METHODS: In both cohorts, patients initially received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day). RESULTS: In the total population (N = 323), the following decreases from baseline to after ibrutinib lead-in were observed: percentage of patients with a lymph node diameter ≥5 cm decreased from 31% to 4%, with absolute lymphocyte count ≥25 × 109/L from 76% to 65%, with high tumor burden category for TLS risk from 23% to 2%, and with an indication for hospitalization (high TLS risk, or medium TLS risk and creatinine clearance <80 mL/minute) from 43% to 18%. Laboratory TLS per Howard criteria occurred in one patient; no clinical TLS was observed. CONCLUSIONS: Three cycles of ibrutinib lead-in before venetoclax initiation provides effective tumor debulking, decreases the TLS risk category and reduces the need for hospitalization for intensive monitoring for TLS.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Síndrome de Lisis Tumoral , Adenina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Creatinina/uso terapéutico , Procedimientos Quirúrgicos de Citorreducción , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/patología , Neoplasia Residual/tratamiento farmacológico , Piperidinas , Sulfonamidas , Síndrome de Lisis Tumoral/tratamiento farmacológico , Síndrome de Lisis Tumoral/etiología
14.
J Chem Phys ; 156(11): 114110, 2022 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-35317590

RESUMEN

Quantifying charge-state transition energy levels of impurities in semiconductors is critical to understanding and engineering their optoelectronic properties for applications ranging from solar photovoltaics to infrared lasers. While these transition levels can be measured and calculated accurately, such efforts are time-consuming and more rapid prediction methods would be beneficial. Here, we significantly reduce the time typically required to predict impurity transition levels using multi-fidelity datasets and a machine learning approach employing features based on elemental properties and impurity positions. We use transition levels obtained from low-fidelity (i.e., local-density approximation or generalized gradient approximation) density functional theory (DFT) calculations, corrected using a recently proposed modified band alignment scheme, which well-approximates transition levels from high-fidelity DFT (i.e., hybrid HSE06). The model fit to the large multi-fidelity database shows improved accuracy compared to the models trained on the more limited high-fidelity values. Crucially, in our approach, when using the multi-fidelity data, high-fidelity values are not required for model training, significantly reducing the computational cost required for training the model. Our machine learning model of transition levels has a root mean squared (mean absolute) error of 0.36 (0.27) eV vs high-fidelity hybrid functional values when averaged over 14 semiconductor systems from the II-VI and III-V families. As a guide for use on other systems, we assessed the model on simulated data to show the expected accuracy level as a function of bandgap for new materials of interest. Finally, we use the model to predict a complete space of impurity charge-state transition levels in all zinc blende III-V and II-VI systems.

15.
Blood ; 139(22): 3278-3289, 2022 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-35196370

RESUMEN

CAPTIVATE (NCT02910583) is an international phase 2 study in patients aged ≤70 years with previously untreated chronic lymphocytic leukemia (CLL). Results from the cohort investigating fixed-duration (FD) treatment with ibrutinib plus venetoclax are reported. Patients received 3 cycles of ibrutinib lead-in then 12 cycles of ibrutinib plus venetoclax (oral ibrutinib [420 mg/d]; oral venetoclax [5-week ramp-up to 400 mg/d]). The primary endpoint was complete response (CR) rate. Hypothesis testing was performed for patients without del(17p) with prespecified analyses in all treated patients. Secondary endpoints included undetectable minimal residual disease (uMRD) rates, progression-free survival (PFS), overall survival (OS), and safety. Of the 159 patients enrolled and treated, 136 were without del(17p). The median time on study was 27.9 months, and 92% of patients completed all planned treatment. The primary endpoint was met, with a CR rate of 56% (95% confidence interval [CI], 48-64) in patients without del(17p), significantly higher than the prespecified 37% minimum rate (P < .0001). In the all-treated population, CR rate was 55% (95% CI, 48-63); best uMRD rates were 77% (peripheral blood [PB]) and 60% (bone marrow [BM]); 24-month PFS and OS rates were 95% and 98%, respectively. At baseline, 21% of patients were in the high tumor burden category for tumor lysis syndrome (TLS) risk; after ibrutinib lead-in, only 1% remained in this category. The most common grade ≥3 adverse events (AEs) were neutropenia (33%) and hypertension (6%). First-line ibrutinib plus venetoclax represents the first all-oral, once-daily, chemotherapy-free FD regimen for patients with CLL. FD ibrutinib plus venetoclax achieved deep, durable responses and promising PFS, including in patients with high-risk features.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Adenina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Humanos , Neoplasia Residual/etiología , Piperidinas , Sulfonamidas
16.
Acc Chem Res ; 55(3): 298-308, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-35050573

RESUMEN

ConspectusThe transition from fossil fuels to renewable energy requires the development of efficient and cost-effective energy storage technologies. A promising way forward is to harness the energy of intermittent renewable sources, such as solar and wind, to perform (electro)catalytic reactions to generate fuels, thus storing energy in the form of chemical bonds. However, current catalysts rely on the use of expensive, rare, or geographically localized elements, such as platinum. Widespread adoption of new (electro)catalytic technologies hinges on the discovery and development of materials containing earth-abundant elements, which can efficiently catalyze an array of (electro)chemical reactions.In the context of catalysis, descriptors provide correlations between fundamental physical properties, such as the electronic structure, and the resulting catalytic activity. The use of easily accessible descriptors has proven to be a powerful method to advance and accelerate discovery and design of new catalyst materials. The position of the oxygen electronic 2p band center has been proposed to capture the basic physical properties of oxides, including oxygen vacancy formation energy, diffusion barrier of oxygen ions, and work function. Moreover, the adsorption strength of relevant reaction intermediates at the surface of oxides can be strongly correlated with the energy of the oxygen 2p states, which affects the catalytic activity of reactions, such as oxygen electrocatalysis, and oxidative dehydrogenation of organic molecules. Such descriptors for catalytic activity can be used to predict the activity of new catalysts and understand trends and behavior among different catalysts.In this Account, we discuss how the energy of the oxygen 2p states can be used as a descriptor for oxide bulk and surface chemical properties. We show how the oxide redox properties vary linearly with the position of the oxygen 2p band center with respect to the Fermi level, and we discuss how this descriptor can be expanded across different materials and structural families, including possible generalizations to compounds outside oxides. We highlight the power of the oxygen 2p band center to predict the catalytic activity of oxides. We conclude with an outlook examining under which conditions this descriptor can be applied to predict oxide properties and possible opportunities for further refining and accelerating property predictions of oxides by leveraging material databases and machine learning.

17.
Pain Physician ; 25(1): 77-85, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35051147

RESUMEN

BACKGROUND: Post-traumatic stress disorder (PTSD) is a prevalent and debilitating condition in the United States. Success rates for evidence-based therapies are inconsistent, and many suffer in silence due to the stigmata associated with seeking traditional mental health care. This has led clinicians to explore new therapeutic options, with cervical sympathetic blockade (CSB), performed at the stellate and/or superior cervical ganglion levels, recently emerging as a promising treatment option. Rapid therapeutic onset, improved compliance, and high clinical efficacy rates have made this an attractive approach for both providers and patients. However, to date, CSB as a treatment of PTSD has primarily been used in male patients with military-related trauma. OBJECTIVE: To evaluate the efficacy of CSB as a treatment option for PTSD in both genders and multiple etiologies of psychological trauma. STUDY DESIGN: Retrospective cohort study. SETTING: An established anesthesia pain clinic in Chicago, IL, USA. METHODS: Following retroactive IRB approval, 484 consecutive cases of patients diagnosed with PTSD and treated with CSB, performed by a single provider (December 2016 - February 2020) were analyzed. The primary outcome measurement was the PTSD Checklist Score version DSM IV (PCL-4). Patient demographic and clinical information collected included age, gender, type of trauma leading to PTSD, history of suicidal attempts, and psychiatric medication use. RESULTS: After exclusion of cases due to missing data points, 327 patients were included in the final statistical analysis, having completed both PCL-4 pre and post CSB, between 7- and 30-days post-intervention. The patient population included military men (n = 97), civilian men (n = 85), military women (n = 13) and civilian women (n = 132). We identified 21 types of self-reported trauma leading to PTSD. Average decrease in PCL score for men and women was 28.59 and 29.2, respectively. Statistical analysis of the male population with a military background showed a significantly greater change in corresponding PCL scores than civilians (PCL-M change = -31.83 vs PCL-C change = -24.89). Likewise, women who had a military background had a significantly greater reduction in PCL score than civilians (39.15 vs 28.23). Statistically significant improvements in PTSD symptoms were noted independent of the causative trauma type, gender, age greater than 20, previous suicide attempts, or use of prescription medications for PTSD. Among the 21 types of reported trauma, 19 types reached statistical significance. LIMITATIONS: Limitations include the limited scope of observation giving exclusive focus on pre- and post-PCL data, the limited duration of observation, the self-reported nature of the patient-provided data, and the provision of treatment by a single physician. CONCLUSION: CSB seems to be an effective treatment for PTSD symptoms irrespective of gender, trauma type, PTSD-related drug use, suicide attempt, or age.


Asunto(s)
Bloqueo Nervioso Autónomo , Personal Militar , Trastornos por Estrés Postraumático , Bloqueo Nervioso Autónomo/efectos adversos , Femenino , Humanos , Masculino , Personal Militar/psicología , Estudios Retrospectivos , Autoinforme , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/terapia , Estados Unidos
18.
Pain Physician ; 25(1): 87-93, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35051148

RESUMEN

BACKGROUND: It is well established that the experience of chronic pain significantly differs among ethnic-racial groups. There is mixed evidence to suggest that societal influences may contribute to pain prevalence among cultural groups and their treatment response. One possible explanation for differences in pain experience are the differences in socioeconomic status among patients with chronic pain. OBJECTIVE: To determine whether there is any difference in pain scores or treatment responses among patients with different socioeconomic status. STUDY DESIGN: Retrospective analysis. SETTING: Outpatient pain clinic. METHODS: After approval from the Advocate Healthcare Institutional Review Board, we included 1,149 patients treated for different chronic pain conditions who were followed for at least 12 months. Patients were stratified into quartiles determined by median income according to ZIP code. RESULTS: Of the sampled patients, 207 patients lived in ZIP codes with median incomes > $51,294; 515 in ZIP codes with median incomes between $40,083 and $51,294; 332 in ZIP  codes with median incomes between $30,625 and $40,083; and 95 in ZIP codes with median incomes < $30,625. Groups differed in age (P = 0.047), race (P < 0.001), body mass index (BMI) (P = 0.019), utilization of opioid medications (P = 0.011), morphine milligram equivalents (MME) on first visit (P = 0.036), and utilization of membrane stabilizers such as gabapentin (P = 0.019). There were no significant differences among groups in terms of gender (P = 0.531), type of pain experienced (P = 0.679), or time since pain onset (P = 0.174). Groups were treated similarly, with no statistically significant differences in the proportions of patients who had taken various nonopioid medications throughout their treatment course other than membrane stabilizers, the number of patients who received interventional pain management procedures, or MME at last visit. Average pretreatment numeric rating scale pain scores were not significantly different among quartiles (P = 0.079), posttreatment pain scores (P = 0.767), and subjective percent improvement (P = 0.434). LIMITATIONS: This is a single center study and may have limitations in extrapolating to the general population. CONCLUSION: The results of our study show that there are no differences in pain perception or treatment responses in patients from different socioeconomic statuses despite differences among groups in age, BMI, race, utilization of opioid medications, and MME at first visit. Patients at this pain practice appear to have been treated with similar modalities regardless of socioeconomic status.


Asunto(s)
Dolor Crónico , Manejo del Dolor , Chicago , Dolor Crónico/terapia , Humanos , Manejo del Dolor/métodos , Estudios Retrospectivos , Factores Socioeconómicos
20.
J Clin Oncol ; 39(34): 3853-3865, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34618601

RESUMEN

PURPOSE: CAPTIVATE (NCT02910583), a randomized phase II study, evaluates minimal residual disease (MRD)-guided treatment discontinuation following completion of first-line ibrutinib plus venetoclax treatment in patients with chronic lymphocytic leukemia (CLL). METHODS: Previously untreated CLL patients age < 70 years received three cycles of ibrutinib and then 12 cycles of combined ibrutinib plus venetoclax. Patients in the MRD cohort who met the stringent random assignment criteria for confirmed undetectable MRD (Confirmed uMRD) were randomly assigned 1:1 to double-blind placebo or ibrutinib; patients without Confirmed uMRD (uMRD Not Confirmed) were randomly assigned 1:1 to open-label ibrutinib or ibrutinib plus venetoclax. Primary end point was 1-year disease-free survival (DFS) rate with placebo versus ibrutinib in the Confirmed uMRD population. Secondary end points included response rates, uMRD, and safety. RESULTS: One hundred sixty-four patients initiated three cycles of ibrutinib lead-in. After 12 cycles of ibrutinib plus venetoclax, best uMRD response rates were 75% (peripheral blood) and 68% (bone marrow). Patients with Confirmed uMRD were randomly assigned to receive placebo (n = 43) or ibrutinib (n = 43); patients with uMRD Not Confirmed were randomly assigned to ibrutinib (n = 31) or ibrutinib plus venetoclax (n = 32). Median follow-up was 31.3 months. One-year DFS rate was not significantly different between placebo (95%) and ibrutinib (100%; arm difference: 4.7% [95% CI, -1.6 to 10.9]; P = .15) in the Confirmed uMRD population. After ibrutinib lead-in tumor debulking, 36 of 40 patients (90%) with high tumor lysis syndrome risk at baseline shifted to medium or low tumor lysis syndrome risk categories. Adverse events were most frequent during the first 6 months of ibrutinib plus venetoclax and generally decreased over time. CONCLUSION: The 1-year DFS rate of 95% in placebo-randomly assigned patients with Confirmed uMRD suggests the potential for fixed-duration treatment with this all-oral, once-daily, chemotherapy-free regimen in first-line CLL.


Asunto(s)
Adenina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Neoplasia Residual/tratamiento farmacológico , Piperidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Adenina/farmacología , Adenina/uso terapéutico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Estudios de Cohortes , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Piperidinas/farmacología , Sulfonamidas/farmacología , Análisis de Supervivencia
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...