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2.
J Helminthol ; 98: e28, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38516701

RESUMO

A new species of trematode of anaporrhutine gorgoderid, from the gill chambers of the Munda round ray Urotrygon munda in Costa Rica is described, based on an integrative taxonomic approach that includes the use of light and scanning electron microscopy, ITS2 and 28S rDNA sequencing, and phylogenetic analysis. Anaporrhutum mundae sp. nov. can be distinguished from congeneric species by a combination of morphological traits and particularly by having the genital pore opening at the level of the intestinal bifurcation. The new species also can be distinguished from all other species of Anaporrhutum, except A. euzeti Curran, Blend & Overstreet, 2003, by having fewer testicular follicles per testis. Anaporrhutum mundae sp. nov. also differs from A. euzeti in its forebody shape and by having different morphology and location of the vitellaria. The study of the tegumental surface of A. mundae sp. nov., as revealed by scanning electron microscopy, allowed detection of new morphological characters for a member of Anaporrhutinae that may be of taxonomic value. These are: a stylet cavity dorsal to the oral sucker with a large penetration gland opening on each side of the cavity and small penetration gland openings located ventral to the stylet cavity, arranged in a circle around the mouth. This represents the first record of an Anaporrhutum species from Costa Rica. Further, A. mundae sp. nov. represents the first parasite described or reported in this host.


Assuntos
Parasitos , Trematódeos , Infecções por Trematódeos , Masculino , Animais , Infecções por Trematódeos/parasitologia , Filogenia , Costa Rica
3.
Front Artif Intell ; 7: 1323512, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500672

RESUMO

This study focuses on the role of AI in shaping Generation Z's consumer behaviors across fashion, technology, beauty, and education sectors. Analyzing responses from 224 participants, our findings reveal that AI exposure, attitude toward AI, and AI accuracy perception significantly enhance brand trust, which in turn positively impacts purchasing decisions. Notably, flow experience acts as a mediator between brand trust and purchasing decisions. These insights underscore the critical role of AI in developing brand trust and influencing purchasing choices among Generation Z, offering valuable implications for marketers in an increasingly digital landscape.

4.
Leuk Lymphoma ; : 1-8, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538632

RESUMO

Olutasidenib, a potent, selective, oral, mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor, is FDA-approved for relapsed/refractory (R/R) acute myeloid leukemia (AML). Here we report efficacy and safety of olutasidenib in 18 patients with mIDH1 AML who were relapsed (10), refractory (6) or had complete remission with incomplete hematologic recovery (CRi; 2) to a venetoclax combination. Of the 16 patients who were R/R, 4 (25%) achieved complete remission (CR), one (6.3%) achieved CR with partial hematologic recovery (CRh), and 7 (43.8%) achieved a composite complete remission (CRc). Median time to CRc was 1.9 months (range 1-2.8). As of data cutoff (18 June 2021), median duration of CRc was not reached (range, 1.2-NR, ongoing at 30.4+ months). Both patients with CRi at study entry achieved a CR. Safety was consistent with the overall profile of olutasidenib. Olutasidenib offers a valuable treatment option for patients with mIDH1 AML previously treated with venetoclax.

6.
Antibiotics (Basel) ; 13(3)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38534709

RESUMO

The aim of this study was to evaluate the effect of inappropriate therapy in adult patients with community-acquired pyelonephritis caused by Escherichia coli receiving empirical treatment with cefuroxime during hospital stay and readmission. A retrospective cohort study was performed. Inappropriate treatment was considered treatment for a nonsusceptible isolate according to the results of the urine culture. Adjustment for confounding factors was performed with propensity score-derived inverse probability of treatment weighting. Between 2013 and 2020, 747 patients were included, 102 (13.7%) of whom received inappropriate therapy. Compared to appropriate therapy, inappropriate therapy was associated with a shorter length of stay in the adjusted analysis (Hazard Ratio = 0.34; 95% CI = 0.23-0.49). After 735 patients were discharged from the hospital, 66 were readmitted in the following 30 days. In comparison with appropriate therapy, inappropriate antimicrobial therapy was not related to readmission (OR 1.47; 95% CI = 0.35-2.79). Inappropriate therapy was not related to a longer hospital stay or readmission due to pyelonephritis after adjusting for confounders and covariates.

7.
Am J Cancer Res ; 14(1): 182-191, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323294

RESUMO

The increase of early-onset colorectal cancer (CRC) among younger adults is a major public health concern. However, little is known about variations in CRC incidence across different age groups within small geographic areas in Georgia. We examined temporal trends of CRC incidence in Clayton, East Central, West Central, Northeast, and Southeast regions, by age groups. Annual incidence rates for CRC in individuals aged 15+ years during 2000-2020 in the five regions of Georgia were included. Temporal trends were examined within the five regions and stratified by age group. Joinpoint regression was employed to calculate the annual percent change and corresponding 95% confidence intervals (CIs). Among 20,215 CRC diagnoses, CRC incidence declined over time for East Central (-2.33%; 95% CI, -3.03, -1.64), Northeast (-1.63%; 95% CI, -2.15, -1.04), Southeast (-1.63%; 95% CI, -2.30, -0.96), and West Central (-1.53%; 95% CI, -2.04, -1.03) Georgia. In the 15-44 age group, a notable increase of CRC incidence was found in Clayton, Northeast, and Southeast regions with a range of 2.2%-3.4%. However, adults aged 60+ years experienced a significant decrease in CRC incidence for most Georgia regions (all p-value <0.05), except for the Clayton region. In conclusion, CRC incidence declined during 2000-2020 in most Georgia regions. However, early-onset CRC is a major concern in Georgia as young adults (<45 years) living in Clayton, Northeast, and Southeast Georgia experienced significant annual increases in CRC incidence. Targeted CRC screening and awareness campaigns should be prioritized for adults <45 years and in the most impacted areas in Georgia.

8.
J Ethnopharmacol ; 326: 117924, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38369067

RESUMO

ETHNOPHARMACOLOGICAL IMPORTANCE: Cucurbita ficifolia Bouché fruit is widely used in Mexican traditional medicine to treat type 2 diabetes (T2D) because it has been attributed with antioxidant and hypoglycemic properties in different experimental models and T2D patients. An imbalance in physiological glutathione (GSH) concentrations increases the susceptibility to developing complications associated with oxidative stress in T2D patients. AIM OF THE STUDY: To investigate the effect of C. ficifolia on the antioxidant properties of GSH, general health measurements, and biochemical parameters in a Mexican rural population, and to evaluate the changes in socio-affective scores of patients due to improvement in T2D. MATERIALS AND METHODS: Twenty-seven women diagnosed with T2D with poor glycemic control volunteered and were divided into two groups: C. ficifolia (0.5 g/kg of fresh pulp weight) with hypoglycemic pharmacotherapy, and another group with only hypoglycemic pharmacotherapy, for 12 weeks. We evaluated the effect of the fresh pulp of C. ficifolia on body mass index, blood pressure, glucose, glycosylated hemoglobin, cholesterol, triglycerides, and GSH. Expanding the study, we evaluated the quality of life, anxiety, and depression scores before and after the intervention. RESULTS: Treatment with the fresh pulp of C. ficifolia for 12 weeks reduced glycosylated hemoglobin, similar to the hypoglycemic pharmacotherapy group, and significantly increased GSH concentrations. The patients' moods did not change despite increased GSH concentrations and improved T2D control. CONCLUSIONS: The increased GSH concentrations due to the consumption of fresh pulp of C. ficifolia could help to protect against oxidative stress and extend therapeutic benefits in addition to the usual hypoglycemic drugs in patients with T2D.


Assuntos
Cucurbita , Diabetes Mellitus Tipo 2 , Humanos , Feminino , Cucurbita/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Extratos Vegetais/farmacologia , Fitoterapia , Qualidade de Vida , População Rural , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Glutationa , Glicemia
9.
Nutr. clín. diet. hosp ; 44(1): 310-317, Feb. 2024. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-231327

RESUMO

Introducción: En años reciente se señalado que trastor-nos como la obesidad, la diabetes mellitus tipo 2 (DMT-II) es-tán asociados a deterioro cognitivo. Una posibilidad para com-prender la relación entre la cognición y estos trastornos sonlos biomarcadores en sangre. Objetivo: El objetivo de esta investigación fue determinarla relación de la hemoglobina glucosilada (HbA1c) y lípidoscon el desempeño cognitivo de pacientes que están expues-tos varios factores de riesgo vascular en comparación con pa-cientes que tienen menos factores de riesgo. Metodología: Se llevó a cabo un muestreo no probabilís-tico por conveniencia. Se consideraron a adultos de ambossexos que tuvieran una edad mayor a 18 años y que conta-ran con algún factor de riesgo como un estilo de vida seden-tario y/o diagnóstico de DMT-II, hipertensión u obesidad. Losparticipantes (n=28) fueron evaluados mediante EvaluaciónCognitiva Montreal (MoCA) y tareas para evaluar memoria detrabajo verbal y visoespacial (Dspan y Mspan). Asimismo, sedeterminaron los niveles de hemoglobina glicosilada (HbA1c),colesterol (HDL y LDL) y triglicéridos (TG). Resultados: Se encontró que los niveles elevados deHbA1c y TG se asociaron con una menor puntuación en laprueba MoCA, mientras que los niveles elevados de HDL seasociaron con mejor desempeño cognitivo en dicha prueba.Al dividir a la muestra en función de la cantidad de factoresde riesgo vascular a los que han sido expuestos se encon-tró que a mayor presencia de factores de riesgo la relaciónde la HbA1c y TG con un menor desempeño cognitivo esmás fuerte. Conclusión: Se concluye que la relación entre biomarca-dores y funciones cerebrales es fuerte y dependiente de lacantidad de factores de riesgo vascular a los que están ex-puestos los pacientes.(AU)


Introduction: In recent years it has been reported thatdisorders such as obesity and type 2 diabetes mellitus (T2DM)are associated with cognitive impairment. One possibility tounderstand the relationship between cognition and these dis-orders is blood biomarkers. Objective: The aim of this research was to determine therelationship of glycosylated hemoglobin (HbA1c) and lipidswith cognitive performance in patients who are exposed tovarious vascular risk factors compared with patients who havefewer risk factors. Methodology: Non-probability convenience sampling wasperformed. Adults of both sexes who were older than 18 years of age and who had some risk factor such as a sedentarylifestyle and/or diagnosis of T2DM, hypertension, or obesitywere considered. Participants (n=28) were assessed byMontreal Cognitive Assessment (MoCA) and tasks to evaluateverbal and visuospatial working memory (Dspan and Mspan).Glycosylated hemoglobin (HbA1c), cholesterol (HDL and LDL)and triglycerides (TG) levels were also determined. Results: It was found that elevated HbA1c and TG levelswere associated with a lower score on the MoCA test, whileelevated HDL levels were associated with better cognitive per-formance on the MoCA test. When the sample was divided ac-cording to the number of vascular risk factors to which theyhad been exposed, it was found that the greater the presenceof risk factors the stronger the relationship of HbA1c and TGwith poorer cognitive performance. Conclusion: We conclude that the relationship betweenbiomarkers and brain function is strong and dependent on thenumber of vascular risk factors to which patients are exposed.(AU)


Assuntos
Humanos , Masculino , Feminino , Cognição , Biomarcadores , Lipídeos , Obesidade , Diabetes Mellitus Tipo 2 , Ciências da Nutrição , Estilo de Vida , Glucose , Alimentos, Dieta e Nutrição
10.
Pathogens ; 13(2)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38392836

RESUMO

BACKGROUND: Drug-resistant tuberculosis (TB) is associated with higher mortality rates in patients with human immunodeficiency virus (HIV). In Mexico, the number of deaths due to TB among the HIV-positive population has tripled in recent years. METHODS: Ninety-three Mycobacterium tuberculosis strains isolated from the same number of HIV-infected patients treated in a public hospital in Mexico City were studied to determine the drug resistance to first- and second-line anti-TB drugs and to identify the mutations associated with the resistance. RESULTS: Of the 93 patients, 82.7% were new TB cases, 86% were male, and 73% had extrapulmonary TB. Most patients (94%) with a CD4 T-lymphocyte count <350 cells/mm3 were associated with extrapulmonary TB (p <0.0001), whilst most patients (78%) with a CD4 T-lymphocyte count >350 cells/mm3 were associated with pulmonary TB (p = 0.0011). Eighty-two strains were pan-susceptible, four mono-resistant, four poly-resistant, two multidrug-resistant, and one was extensively drug-resistant. In the rifampicin-resistant strains, rpoB S531L was the mutation most frequently identified, whereas the inhA C15T and katG S315T1 mutations were present in isoniazid-resistant strains. The extensively drug-resistant strain also contained the mutation gyrA D94A. CONCLUSIONS: These data highlight the need to promptly diagnose the drug resistance of M. tuberculosis among all HIV-infected patients by systematically offering access to first- and second-line drug susceptibility testing and to tailor the treatment regimen based on the resistance patterns to reduce the number of deaths in HIV-infected patients.

11.
Blood ; 143(10): 858-865, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38194683

RESUMO

ABSTRACT: Tyrosine kinase inhibitors (TKIs) are standard therapy for patients with chronic myeloid leukemia. Each of these drugs has a specific profile of tyrosine kinases that they inhibit and, although all are clinically effective, they each have unique toxicity profiles. With the introduction of ponatinib, arterio-occlusive events were first noted and later found to occur with all TKIs to various extents. The recognition of this "class effect" was delayed considering ponatinib was introduced 10 years after the introduction of imatinib. The reasons for the delay in identification of this class effect are likely multifaceted. Importantly, there is an inconsistency in adverse event reporting criteria among the major clinical trials of the various TKIs, likely resulting in mixed reporting of arterio-occlusive events. Reporting events based on a frequency threshold, lack of sufficient follow-up, attempts at causality attribution, and the primary focus on molecular response may all have played an additional role. Considering the increasing rate of arterio-occlusive events over time, the termination of many trials after only 5 years prevents full assessment of the impact of these events. A comprehensive evaluation of TKI adverse effects using uniform Medical Dictionary for Regulatory Activities terms and comprehensive adjudication of these events may be helpful in better assessing the real risk for patients with each TKI. Future clinical trials should use a uniform and comprehensive approach to reporting adverse events without attempting to assign causality to the study drug.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Antineoplásicos/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico
13.
Syst Rev ; 13(1): 30, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38229123

RESUMO

BACKGROUND: The interaction between modelers and policymakers is becoming more common due to the increase in computing speed seen in recent decades. The recent pandemic caused by the SARS-CoV-2 virus was no exception. Thus, this study aims to identify and assess epidemiological mathematical models of SARS-CoV-2 applied to real-world data, including immunization for coronavirus 2019 (COVID-19). METHODOLOGY: PubMed, JSTOR, medRxiv, LILACS, EconLit, and other databases were searched for studies employing epidemiological mathematical models of SARS-CoV-2 applied to real-world data. We summarized the information qualitatively, and each article included was assessed for bias risk using the Joanna Briggs Institute (JBI) and PROBAST checklist tool. The PROSPERO registration number is CRD42022344542. FINDINGS: In total, 5646 articles were retrieved, of which 411 were included. Most of the information was published in 2021. The countries with the highest number of studies were the United States, Canada, China, and the United Kingdom; no studies were found in low-income countries. The SEIR model (susceptible, exposed, infectious, and recovered) was the most frequently used approach, followed by agent-based modeling. Moreover, the most commonly used software were R, Matlab, and Python, with the most recurring health outcomes being death and recovery. According to the JBI assessment, 61.4% of articles were considered to have a low risk of bias. INTERPRETATION: The utilization of mathematical models increased following the onset of the SARS-CoV-2 pandemic. Stakeholders have begun to incorporate these analytical tools more extensively into public policy, enabling the construction of various scenarios for public health. This contribution adds value to informed decision-making. Therefore, understanding their advancements, strengths, and limitations is essential.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Estados Unidos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Vacinação , Avaliação de Resultados em Cuidados de Saúde
14.
Leukemia ; 38(3): 475-481, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38287132

RESUMO

Ponatinib, the only approved all known-BCR::ABL1 inhibitor, is a third-generation tyrosine-kinase inhibitor (TKI) designed to inhibit BCR::ABL1 with or without any single resistance mutation, including T315I, and induced robust and durable responses at 45 mg/day in patients with CP-CML resistant to second-generation TKIs in the PACE trial. However, cardiovascular toxicities, including arterial occlusive events (AOEs), have emerged as treatment-related AEs within this class of TKIs. The OPTIC trial evaluated the efficacy and safety of ponatinib using a novel, response-based, dose-reduction strategy in patients with CP-CML whose disease is resistant to ≥2 TKIs or who harbor T315I. To assess the dose-response relationship and the effect on the safety of ponatinib, we examined the outcomes of patients with CP-CML enrolled in PACE and OPTIC who received 45 mg/day of ponatinib. A propensity score analysis was used to evaluate AOEs across both trials. Survival rates and median time to achieve ≤1% BCR::ABL1IS in OPTIC were similar or better than in PACE. The outcomes of patients with T315I mutations were robust in both trials. Patients in OPTIC had a lower exposure-adjusted incidence of AOEs compared with those in PACE. This analysis demonstrates that response-based dosing for ponatinib improves treatment tolerance and mitigates cardiovascular risk.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide de Fase Crônica , Piridazinas , Humanos , Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Imidazóis/uso terapêutico , Imidazóis/farmacologia , Piridazinas/uso terapêutico , Piridazinas/farmacologia , Proteínas de Fusão bcr-abl/genética , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia
15.
Gynecol Oncol ; 181: 141-154, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38163384

RESUMO

OBJECTIVE: This systematic review aimed to investigate what are the most relevant social determinants of health (SDH), how they are measured, how they interact among themselves and what is their impact on the outcomes of cervical cancer patients. METHODS: Search was performed in PubMed, Scopus, Web of Science, Embase, Cochrane, and Google Scholar databases from January 2001 to September 2022. The protocol was registered at PROSPERO (CRD42022346854). We followed the PICOS strategy: Population- Patients treated for cervical cancer in the United States; Intervention - Any SDH; Comparison- None; Outcome measures- Cancer treatment outcomes related to the survival of the patients; Types of studies- Observational studies. Two reviewers extracted the data following the PRISMA guidelines. Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies was used for risk of bias (ROB) assessment. RESULTS: Twenty-four studies were included (22 had low and 2 had moderate ROB). Most manuscripts analyzed data from public registries (83.3%) and only one SDH (54.17%). The SDH category of Neighborhood was not included in any study. Although the SDH were measured differently across the studies, not being married, receiving treatment at a low-volume hospital, and having public insurance (Medicaid or Medicare) or not being insured was associated with shorter survival of cervical cancer patients in most studies. CONCLUSIONS: There is a deficit in the number of studies comprehensively assessing the impact of SDH on cervical cancer treatment-related outcomes. Marital status, hospital volume and health insurance status are potential predictors of worse outcome.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Idoso , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/terapia , Determinantes Sociais da Saúde , Estudos Transversais , Medicare , Hospitais com Baixo Volume de Atendimentos
16.
Cancer Med ; 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38164120

RESUMO

PURPOSE: Investigating CRC screening rates and rurality at the county-level may explain disparities in CRC survival in Georgia. Although a few studies examined the relationship of CRC screening rates, rurality, and/or CRC outcomes, they either used an ecological study design or focused on the larger population. METHODS: We conducted a retrospective analysis utilizing data from the 2004-2010 Surveillance, Epidemiology, and End Results Program. The 2013 United States Department of Agriculture rural-urban continuum codes and 2004-2010 National Cancer Institute small-area estimates for screening behaviors were used to identify county-level rurality and CRC screening rates. Kaplan-Meier method and Cox proportional hazard regression were performed. RESULTS: Among 22,160 CRC patients, 5-year CRC survival rates were lower among CRC patients living in low screening areas in comparison with intermediate/high areas (69.1% vs. 71.6% /71.3%; p-value = 0.030). Patients living in rural high-screening areas also had lower survival rates compared to non-rural areas (68.2% vs. 71.8%; p-value = 0.009). Our multivariable analysis demonstrated that patients living in intermediate (HR, 0.91; 95% CI, 0.85-0.98) and high-screening (HR, 0.92; 95% CI, 0.85-0.99) areas were at 8%-9% reduced risk of CRC death. Further, non-rural CRC patients living in intermediate and high CRC screening areas were 9% (HR, 0.91; 95% CI, 0.83-0.99) and 10% (HR, 0.90; 95% CI, 0.82-0.99) less likely to die from CRC. CONCLUSIONS: Lower 5-year survival rates were observed in low screening and rural high-screening areas. Living in intermediate/high CRC screening areas was negatively associated with the risk of CRC death. Particularly, non-rural patients living in intermediate/high-screening areas were 8%-9% less likely to die from CRC. Targeted CRC screening resources should be prioritized for low screening and rural communities.

17.
Cancer ; 130(2): 287-299, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37801052

RESUMO

BACKGROUND: The authors assessed the clinical utility of patient-reported symptom monitoring in the setting of newly diagnosed chronic myeloid leukemia (CML). The primary objective was to evaluate adherence to therapy. METHODS: The authors conducted an international prospective study that included patients with newly diagnosed, chronic-phase CML. Before clinical consultation, patients were provided a tablet computer to self-rate their symptoms, and the results were available in real time to each physician during the patient's visit. Adherence was assessed by pill count and with a validated self-reported questionnaire. The proportions of optimal responders at 3 and 6 months were assessed according to the European LeukemiaNet criteria. RESULTS: Between July 2020 and August 2021, 94 patients with a median age of 57 years were enrolled. Pill count adherence analysis indicated that 86 of 93 evaluable patients (92.5%) took at least 90% of prescribed tyrosine kinase inhibitor therapy during the 6-month observation period. The online platform was well accepted by patients and physicians. An optimal response was achieved by 69 of 79 patients (87.3%) at 3 months and by 61 of 81 patients (75.3%) at 6 months. CONCLUSIONS: Patient-reported symptom monitoring from the beginning of therapy in patients with CML may be critical to improve adherence to therapy and early molecular response rates (ClinicalTrials.gov identifier NCT04384848).


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Pessoa de Meia-Idade , Doença Crônica , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Adesão à Medicação , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos
18.
Mod Pathol ; 37(2): 100406, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38104892

RESUMO

Chronic myeloid leukemia (CML) is characterized by leukocytosis with left-shifted neutrophilia, basophilia, eosinophilia, and variable thrombocytosis. However, extremely rare cases of patients with CML without significant leukocytosis and thrombocytosis (aleukemic phase [ALP] CML, or CML-ALP) have been reported. Due to its rarity and limited awareness, there remains a significant knowledge gap concerning the pathologic diagnosis, disease progression, and optimal patient management and outcomes. In this multi-institutional study, we investigated 31 patients with CML-ALP. Over half (54.8%) of patients had a history of or concurrent hematopoietic or nonhematopoietic malignancies. At time of diagnosis of CML-ALP, approximately 26.7% of patients exhibited neutrophilia, 56.7% had basophilia, and 13.3% showed eosinophilia. The median number of metaphases positive for t(9;22)(q34;q11.2) was 15, with a median of 38.5% of interphase nuclei positive for BCR::ABL1 by fluorescence in situ hybridization. The median BCR::ABL1 level was 26.14%. Remarkably, 14 (45.2%) patients were initially misdiagnosed or not diagnosed before karyotype or fluorescence in situ hybridization information for BCR::ABL1 became available. Twenty-five patients received tyrosine kinase inhibitors (TKIs). One patient developed blast crisis while on TKI treatment 8 months after initial diagnosis. With a median follow-up time of 46.1 months, 20 of 22 patients who received TKI therapy and had detailed follow-up information achieved complete cytogenetic remission or deeper, 15 achieved major molecular remission or deeper, and 10 achieved molecularly undetectable leukemia. In conclusion, given the frequent occurrence of prior or concurrent malignancies, aleukemic presentation, and low level of t(9;22)(q34;q11.2)/BCR::ABL1, misdiagnosis or delayed diagnosis is common among these patients. While these patients generally respond well to TKIs, rare patients may develop blastic transformation. It is therefore important for pathologists and hematologists to be aware of this highly unusual presentation of CML to ensure timely diagnosis and appropriate management.


Assuntos
Eosinofilia , Leucemia Mielogênica Crônica BCR-ABL Positiva , Trombocitose , Humanos , Hibridização in Situ Fluorescente , Leucocitose , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Trombocitose/genética , Inibidores de Proteínas Quinases/uso terapêutico
20.
JAMA Netw Open ; 6(12): e2347950, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38109114

RESUMO

Importance: Patients with chronic myeloid leukemia (CML) who have a sustained deep molecular response using tyrosine kinase inhibitors (TKIs) can safely attempt to stop their use. As these medications are very costly, this change in treatment protocols may result in large savings. Objective: To estimate future savings from attempting to stop TKI use among patients with CML who have deep molecular response. Design, Setting, and Participants: A microsimulation model was developed for this decision analytical modeling study to estimate costs for US adults moving from using a TKI, to attempting discontinuation and then reinitiating TKI therapy, if clinically appropriate. Estimates were calculated for US patients who currently have CML and simulated newly diagnosed cohorts of patients over the next 30 years. Exposure: Attempting to stop using a TKI. Main Outcomes and Measures: Estimated savings after attempted discontinuation of TKI use. Results: A simulated population of individuals with CML in 2018 and future populations were created using estimates from the SEER*Explorer website. The median age at diagnosis was 66 years for men and 65 years for women. Between 2022 and 2052, the savings associated with eligible patients attempting discontinuation of TKI therapy was estimated at more than $30 billion among those currently diagnosed and over $15 billion among those who will develop CML in the future, for a total savings of over $54 billion by 2052 for drug treatment and polymerase chain reaction testing. The estimate is conservative as it does not account for complications and other health care-associated costs for patients continuing TKI therapy. Conclusions and Relevance: The findings of this decision analytical modeling study of patients with CML suggest that attempting discontinuation of TKI therapy could save over $54 billion during the next 30 years. Further education for patients and physicians is needed to safely increase the number of patients who can successfully attain treatment-free remission.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Adulto , Masculino , Humanos , Feminino , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Custos de Cuidados de Saúde , Renda , Pacientes , Inibidores de Proteínas Quinases/uso terapêutico
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