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1.
Expert Opin Emerg Drugs ; 26(2): 103-129, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33734833

RESUMEN

Introduction: Pancreatic adenocarcinoma is now the third-leading cause of cancer-related deaths in the US which can be attributed to rising incidence, diagnosis at advanced stages and early development of metastasis. Systemic therapy remains palliative with early development of resistance possibly related to the constitutive activation of 'undruggable' KRAS, immunosuppressive microenvironment, and intense desmoplasia. The advancements in molecular biology has led to the development and investigation of targeted and immune therapeutics.Areas covered: This study provides a comprehensive review of the literature to further the understanding of molecular targets with their respective antibody-based therapies in clinical development in pancreatic cancer. PubMed was systematically searched for English-language articles discussing antibody-based therapies under phase 2 clinical trial investigation in pancreatic adenocarcinoma.Expert opinion: PDAC remains highly resistant to chemotherapy with no significant improvement in survival for patients with advanced or metastatic cancer. Unfortunately, the majority of the antibody-based targeted and immune therapeutics have failed to meet their primary efficacy endpoints in early phase trials. However, there are a few promising antibody-based drugs with intriguing preliminary data that merit further investigation, while many more continue to be developed and investigated preclinically, and in early phase trials.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/inmunología , Adenocarcinoma/patología , Animales , Anticuerpos Monoclonales/administración & dosificación , Ensayos Clínicos Fase II como Asunto , Diseño de Fármacos , Desarrollo de Medicamentos , Humanos , Terapia Molecular Dirigida , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Microambiente Tumoral
2.
Am J Hematol ; 95(2): 198-204, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31691333

RESUMEN

Impact of Plerixafor (P) mobilized stem cells on immune reconstitution, such as absolute lymphocyte count at day 30 (ALC30), and on long-term outcomes of Multiple Myeloma (MM) patients undergoing autologous stem cell transplant (ASCT) has not been well established. We evaluated total of 469 patients mobilized with G-CSF (G) alone, and 141 patients mobilized with G-CSF plus plerixafor (G+ P). Patients only received plerixafor if they had peripheral blood CD34+ blood count <20/µL on first planned day of collection. Primary endpoint, ALC30, was 1.3 K/µL (range, 0.1-4.5) and 1.2 K/µL (range, 0.1-5.1) for G and G + P, respectively (P =. 61). The median PFS was 2.5 years (95% CI, 2.1-3.2) and 2.8 years (95% CI, 2.0-3.3) for G and G + P, respectively (HR: 1.13; 95% CI, 0.84-1.50; P = .42). The median OS was 6.1 years (95% CI, 4.6-NR) for G group compared to 3.7 years (95% CI, 3.2-NR) for the G + P group (HR: 1.64; 95% CI, 1.12-2.40; P = .01). The median follow-up time for OS was 2.53 years (95% CI, 2.13-2.99) and 1.59 years (95% CI, 1.17-2.02) for G and G+ P group, respectively. In this large retrospective analysis of MM patients mobilized with G-CSF vs G-CSF + P, there was no significant difference in lymphocyte recovery or PFS. There was an overall survival difference in patients who were poor mobilizers and could not be mobilized with G-CSF alone.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos/administración & dosificación , Mieloma Múltiple/terapia , Recuperación de la Función , Adulto , Anciano , Autoinjertos , Bencilaminas , Ciclamas , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad
3.
Asian Pac J Cancer Prev ; 24(10): 3327-3334, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37898835

RESUMEN

OBJECTIVE: It is commonly observed that patients hold certain expectations from hospitals and subsequently feel different levels of satisfaction/realisation after getting treatment from healthcare providers. The present study is focused on examining the pre-hospitalization expectations of cancer patients, as well as their experiences (realisation) with healthcare delivery services. The study also investigated the factors that impact the satisfaction levels of individuals with cancer by utilizing an adapted measurement scale of SERVQUAL. METHODS: A sample of 202 individuals diagnosed with cancer were interviewed. Care was taken to ensure that only those patients who had completed all the requisite treatment procedures were selected for the interviews. All regions of state of Punjab in India, have been included for information. RESULT: The research revealed a notable disparity between the pre-hospitalization expectations of cancer patients regarding the healthcare provisions and the actual delivery (realisation) of such services and the mean difference observed was -1.44. When the difference between expectations and outcomes was observed for the COVID period, the margin widened and the mean difference increased to -2.02. The study also identified six factors that can be utilised to assess patient satisfaction in the Punjab region. CONCLUSION: The study is distinctive in its approach as there is a dearth of research conducted in measuring the level of satisfaction of cancer patients in Punjab state of India. The findings of this study will facilitate cancer hospitals in devising policies that are grounded on the factors that have been identified. Additionally, it will facilitate policymakers in assessing the disparity between the anticipated medical care and the actual medical care that was administered to the patient.


Asunto(s)
Motivación , Neoplasias , Humanos , Hospitales , Hospitalización , Satisfacción del Paciente , Neoplasias/terapia , Calidad de la Atención de Salud
4.
Hematol Oncol Stem Cell Ther ; 17(1): 43-50, 2023 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-37581459

RESUMEN

BACKGROUND AND OBJECTIVE: Hematopoietic stem cell transplant (HSCT) is a well-established treatment for hematologic malignancies and certain autoimmune and congenital conditions. HSCT is associated with immunocompromise and increased risk of infections. This study assessed whether invasive pulmonary aspergillosis (IPA) affects in-hospital mortality and 30-day readmission among HSCT patients. A secondary objective was to examine potential differences in complications between HSCT with and without IPA. MATERIALS AND METHODS: A retrospective study of a nationally representative cohort of hospital admissions was conducted, with data collected from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Readmissions Database between 2013 and 2019. The International Classification of Diseases, 10th revision (ICD-10), and 9th revision (ICD-9) diagnostic codes were used to identify patients with IPA and HSCT. All adult patients ≥18 years were included in the study. RESULTS: There were 90,451 hospitalizations for HSCT from 2013 to 2019; 89,331 (98.8%) had HSCT without IPA, while 1092 (1.2%) hospitalizations had HSCT with IPA. The in-hospital mortality for HSCT-IPA was higher compared to HSCT without IPA (18.3% vs. 4.2%; p < 0.001). HSCT-IPA had a significantly higher 30-day readmission rate (36.2%) than that of HSCT without IPA (24.0%). HSCT-IPA also had a higher mean cost of admission ($303,437) than that of HSCT without IPA ($57,587).The HSCT-IPA group had higher multi-organ complications, including respiratory failure (51.3% vs. 13.5%, p < 0.001), sepsis (38.2% vs. 18.5%, p < 0.001), septic shock (16.1% vs. 5.1%, p < 0.001), need for mechanical ventilation (21.1% vs. 5.1% p < 0.001), non-invasive positive pressure ventilation (4.9% vs. 2.5%, p < 0.001), and intensive-care unit admission (21.8% vs. 6.1% p < 0.001). CONCLUSION: IPA is a rare but severe complication associated with HSCT, with higher in-hospital mortality, complications due to multi-organ failure, readmission rates, and cost of hospitalization when compared to HSCT without IPA.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Aspergilosis Pulmonar Invasiva , Adulto , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hospitalización , Aspergilosis Pulmonar Invasiva/epidemiología , Aspergilosis Pulmonar Invasiva/terapia , Aspergilosis Pulmonar Invasiva/etiología , Readmisión del Paciente , Estudios Retrospectivos , Estados Unidos/epidemiología , Adolescente
5.
Leuk Lymphoma ; 63(4): 813-820, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34781825

RESUMEN

Utilization of novel agents such as brentuximab vedotin (BV) and check-point inhibitors (CI) has increased in patients with relapsed/refractory (r/r) classical Hodgkin Lymphoma (cHL). We conducted a retrospective study of 209 patients who had ASCT for r/r cHL at our institution and compared outcomes of those who had ASCT from 2010-2018 (cohort 2, n = 110) with those who had ASCT between 2000 and 2009 (cohort 1, n = 99). The median OS was 7.6 years for cohort 1 [HR 2.08; 95% CI 1.14-3.80; p = 0.017] and not reached for cohort 2; with 4-year improved OS difference of 15% (80% vs 65%) in cohort 2 vs cohort 1. The median PFS of cohort 1 was 30 months vs 39 months for cohort 2[HR 1.24; 95% CI 0.82-1.88; p = 0.3]. This study highlights improved OS of r/r cHL patients who have received ASCT in the novel agent era due to the exposure to agents such as BV and CIs.


Asunto(s)
Enfermedad de Hodgkin , Inmunoconjugados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Brentuximab Vedotina , Enfermedad de Hodgkin/patología , Humanos , Inmunoconjugados/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Retrospectivos , Trasplante Autólogo
6.
Sci Rep ; 11(1): 22095, 2021 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-34764343

RESUMEN

Strategies promoting efficient water use and conserving irrigation water are needed to attain water security to meet growing food demands. This meta-analysis study evaluated the effect of deficit irrigation (DI) strategy on eight vegetables to provide a quantitative estimate of yield and water productivity (WP) responses under variable soil textures, climates, and production systems (open-field and greenhouse). This study analyzed 425 yield and 388 WP comparisons of different DI levels to full irrigation (FI), extracted from 185 published studies representing 30 countries. Moving from the highest (> 80%FI) to the lowest (< 35%FI) irrigation level, the overall yield decline was 6.9 to 51.1% compared to FI, respectively. The WP gains ranged from 8.1 to 30.1%, with 35-50%FI recording the highest benefits. Soil texture affected the yield significantly only under the least irrigation class (< 35%FI), wherein sandy clay and loam recorded the highest (82.1%) and the lowest (26.9%) yield decline, respectively. Among the climates, temperate climate was overall the most advantageous with the least yield penalty (21.9%) and the highest WP gain (21.78%) across various DI levels. The DI application under the greenhouse caused lesser yield reduction compared to the open-field. The WP gains due to DI were also higher for greenhouse (18.4%) than open-field (13.6%). Consideration of yield penalties and the cost of saved irrigation water is crucial while devising the reduced irrigation amounts to the crops. The yield reductions under low to moderate water deficits (> 65%FI) accompanied by gains in WP may be justifiable in the light of anticipated water restriction.

7.
Cureus ; 12(8): e9625, 2020 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-32923226

RESUMEN

Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell Non-Hodgkin lymphoma (NHL) associated with immunocompromised states such as HIV. We present a case of PBL in an HIV patient presenting as spontaneous tumor lysis syndrome and discuss the clinical challenges hence encountered.

8.
Acta Crystallogr B Struct Sci Cryst Eng Mater ; 74(Pt 4): 376-384, 2018 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-30141423

RESUMEN

The role of different intermolecular interactions in the crystal structures of halogen-substituted indoles which are fused with six-membered or seven-membered cyclic rings is investigated here. Several crystal structures show isostructural characteristics due to the presence of similar supramolecular motifs. In the absence of any strong hydrogen bonds, the molecular packing of reported structures is primarily stabilized by the presence of non-classical N-H...π and C-H...π interactions in addition to C-H...X (X = F/Cl/Br) interactions. The nature and energetics of primary and secondary dimeric motifs are partitioned into the electrostatics, polarization, dispersion and exchange-repulsion components using the PIXEL method. Short and directional N-H...π interactions are further explored by a topological analysis of the electron density based on quantum theory of atoms in molecules.

9.
Tex Heart Inst J ; 42(5): 495-7, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26504451

RESUMEN

Magnesium is known to act at the neuromuscular junction by inhibiting the presynaptic release of acetylcholine and desensitizing the postsynaptic membrane. Because of these effects, magnesium has been postulated to potentiate neuromuscular weakness. We describe the case of a 62-year-old woman with myasthenia gravis and a metastatic thymoma who was admitted to our intensive care unit for management of a myasthenic crisis. The patient's neuromuscular weakness worsened in association with standard intravenous magnesium replacement, and the exacerbated respiratory failure necessitated intubation, mechanical ventilation, and an extended stay in the intensive care unit. The effect of magnesium replacement on myasthenia gravis patients has not been well documented, and we present this case to increase awareness and stimulate research. In addition, we discuss the relevant medical literature.


Asunto(s)
Pulmón/efectos de los fármacos , Sulfato de Magnesio/efectos adversos , Miastenia Gravis/tratamiento farmacológico , Insuficiencia Respiratoria/inducido químicamente , Enfermedad Aguda , Administración Intravenosa , Femenino , Humanos , Pulmón/fisiopatología , Sulfato de Magnesio/administración & dosificación , Persona de Mediana Edad , Miastenia Gravis/complicaciones , Miastenia Gravis/diagnóstico , Miastenia Gravis/fisiopatología , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/fisiopatología , Insuficiencia Respiratoria/terapia , Factores de Tiempo , Resultado del Tratamiento
10.
Med Chem ; 9(3): 371-8, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-22921109

RESUMEN

The present paper describes the design and synthesis of a series of some 2-naphthyloxy derivatives with their antiamnesic activity using mice as the animal model and piracetam as the reference drug. All the synthesized compounds were characterized by spectroscopic techniques and were screened for their efficacy as cognition enhancers by elevated plus maze test and acetylcholinestrase inhibitory assay. Molecular modeling and docking studies of the selected compounds into the crystal structure of acetylcholinestrase complexed with functional ligand succinylcholine using GRAMM software was performed in order to predict the affinity and orientation of the synthesized derivatives at the active site. The binding energy of ligands was calculated using ArgusLab software. The docking score and hydrogen bonds formed with surrounding amino acids show the good agreement with predicted binding affinities obtained by molecular docking studies, as verified by acetylcholinestrase activity.


Asunto(s)
Amnesia/prevención & control , Glicolatos/síntesis química , Glicolatos/farmacología , Simulación de Dinámica Molecular , Nootrópicos/síntesis química , Nootrópicos/farmacología , Animales , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Activación Enzimática/efectos de los fármacos , Glicolatos/química , Enlace de Hidrógeno , Ligandos , Ratones , Estructura Molecular , Nootrópicos/química , Piracetam/química , Piracetam/farmacología , Unión Proteica/efectos de los fármacos
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