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Routine screening of organ donors to detect human immunodeficiency virus (HIV) infection has detected the rare transmission of the virus through organ transplantation. However, despite routine screening, HIV transmission remains a risk in organ transplantation since, unlike tissues, solid organs cannot be processed, disinfected, or modified to inactivate infectious pathogens. A case of possible transmission of HIV by organ transplant is described below, from a previously seronegative donor to two recipients.
El examen de rutina de los donantes de órganos para detectar la infección por el virus de la inmunodeficiencia humana (HIV) ha hecho que la transmisión del virus mediante el trasplante de órganos sea poco común. Sin embargo, a pesar de las pruebas de detección de rutina, la transmisión del HIV continúa siendo un riesgo del trasplante de órganos ya que, a diferencia de los tejidos, los órganos sólidos no se pueden procesar, desinfectar, ni modificar para inactivar patógenos infecciosos. A continuación, se describe un caso de posible transmisión de HIV por trasplante de órganos de un donante previamente seronegativo a dos de sus receptores.
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Infecciones por VIH , Humanos , Infecciones por VIH/transmisión , Masculino , Persona de Mediana Edad , Trasplante de Riñón , Femenino , Adulto , Trasplante de Órganos/efectos adversos , Donantes de TejidosRESUMEN
Background: Evaluating clinical trial representation for countries with different socio-demographic index (SDI) and tyrosine kinase inhibitor (TKI) availability for chronic myeloid leukemia (CML). Methods: CML incidence rates (IRs) and disability-adjusted life years (DALYs) (1999-2019) from the Institute of Health Metrics and Evaluation were analyzed. Trials investigating TKI use in CML were obtained from ClinicalTrials.gov. Site data for eligible trials (N = 30) and DALYs were analyzed. TKI approvals, DALYs, and IRs were summarized by SDI. Results: North America (NA) had significant decreases in annual percent change (APC) in DALYs and incidence rates from 1999 to 2004. IRs were highest in Europe and Central Asia (ECA) and NA, while DALYs were highest in South Asia (SAsia) and Sub-Saharan Africa (SSA). Countries in the high-SDI quintile were likely to have lower DALYs than lower-SDI quintiles. Differences in regional DALYs vs. sites in TKI trials were significant for SAsia, SSA, and ECA. High-SDI countries were included in all 30 trials, and TKI approvals were prominent in high-SDI (142) vs. low-SDI (14) countries. Conclusions: The inclusion of disproportionately affected countries during the design of and recruitment into clinical trials should occur, as should TKI availability. The lack of representation demonstrates healthcare disparities.
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This cross-sectional study examines poverty, rurality, and the intersection of persistent poverty and rurality on early-onset colorectal cancer survival among adults aged 18 to 49 years.
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Neoplasias Colorrectales , Pobreza , Población Rural , Humanos , Neoplasias Colorrectales/mortalidad , Pobreza/estadística & datos numéricos , Masculino , Femenino , Población Rural/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Edad de Inicio , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Both cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. Although our previous study detected a relationship between CVD and cancer incidence, limited evidence is available regarding the relationship between CVD, cardiovascular risk factors, and cancer mortality. METHODS AND RESULTS: A prospective cohort study using data from the continuous NHANES (National Health and Nutrition Examination Survey, 1999-2016) merged with Medicare and National Death Index mortality data, through December 31, 2018. We included individuals with no history of cancer at baseline. The primary exposure was CVD at baseline. We also conducted a comprehensive risk factor analysis as secondary exposure. The main outcome was cancer mortality data collected from Medicare and National Death Index. We included 44 591 adult individuals representing 1 738 423 317 individuals (52% female, 67% non-Hispanic White, and 9% Hispanic). Competing risk modeling showed a significantly higher risk of cancer mortality in individuals with CVD (adjusted hazard ratio [aHR], 1.37 [95% CI 1.07-1.76], P=0.01) after adjusting for age, sex, and race and ethnicity. Notably, cancer mortality increased with aging (aHR, 1.08 [95% CI 1.05-1.11], P<0.0001), current smoking status (aHR, 6.78 [95% CI, 3.43-13.42], P<0.0001), and obesity (aHR, 2.32 [95% CI, 1.13-4.79], P=0.02). Finally, a significant interaction (P=0.034) was found where those with CVD and obesity showed higher cancer mortality than those with normal body mass index (aHR, 1.73 [95% CI, 1.03-2.91], P=0.04). CONCLUSIONS: Our study highlights the close relationship between cardiovascular health and cancer mortality. Our findings suggest that obesity may play a significant role in cancer mortality among individuals with CVD. These findings emphasize the need for a more proactive approach in managing the shared risk factors for CVD and cancer.
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Enfermedades Cardiovasculares , Neoplasias , Encuestas Nutricionales , Humanos , Femenino , Masculino , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/epidemiología , Neoplasias/mortalidad , Neoplasias/epidemiología , Estados Unidos/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Factores de Riesgo , Anciano , Medición de Riesgo/métodos , Causas de Muerte , IncidenciaRESUMEN
Bosutinib is a second-generation tyrosine kinase inhibitor indicated for the treatment of patients with newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia (CML), and for patients with Ph + chronic phase, accelerated phase, or blast phase CML resistant or intolerant to prior therapy. As is the case for all TKIs approved for treatment of CML, bosutinib is associated with adverse events (AEs) that require appropriate management to ensure adherence to treatment and optimized outcomes. The aim of this review is to provide physicians with updated practical information for the prevention and management of AEs occurring during treatment with bosutinib, including dosing strategies, based on the latest published evidence and clinical experience. Clinical studies and real-world evidence have shown bosutinib has a generally favorable safety profile, which has remained consistent across lines of therapy and in long-term reports. Adjusting the starting dose and/or modifying the dose during treatment with bosutinib are important strategies to manage AEs and improve tolerability, which are recognized within the label and in treatment guidelines. Dosing adjustment strategies to manage AEs are a recognized management approach for other TKIs in the treatment of CML and are not exclusive to bosutinib. In summary, long-term results from clinical trials and emerging real-world evidence demonstrate bosutinib has a safety profile that can largely be managed with treatment modifications and/or supportive care. Increased experience in managing toxicities and by using a personalized dosing approach may further improve adherence and outcomes with bosutinib.
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Compuestos de Anilina , Leucemia Mielógena Crónica BCR-ABL Positiva , Nitrilos , Inhibidores de Proteínas Quinasas , Quinolinas , Compuestos de Anilina/uso terapéutico , Compuestos de Anilina/efectos adversos , Nitrilos/uso terapéutico , Nitrilos/efectos adversos , Humanos , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Quinolinas/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversosRESUMEN
This study investigates COVID-19 outcomes and immune response in chronic myeloid leukemia (CML) patients post-SARS-CoV-2 vaccination, comparing effectiveness of various vaccine options. Data from 118 CML patients (85 in Brazil, 33 in the US) showed similar infection rates prior (14% Brazil, 9.1% US) and post-vaccination (24.7% vs. 27.3%, respectively). In Brazil, AstraZeneca and CoronaVac were the most commonly used vaccine brands, while in the US, Moderna and Pfizer-BioNTech vaccines dominated. Despite lower seroconversion in the Brazilian cohort, all five vaccine brands analyzed prevented severe COVID-19. Patients who received mRNA and recombinant viral vector vaccines (HR: 2.20; 95%CI 1.07-4.51; p < .031) and those that had achieved at least major molecular response (HR: 1.51; 95% CI 1.01-3.31; p < .0001) showed higher seroconversion rates. Our findings suggest that CML patients can generate antibody responses regardless of the vaccine brand, thereby mitigating severe COVID-19. This effect is more pronounced in patients with well-controlled disease.
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Tyrosine kinase inhibitors (TKI) have improved the outcome and life expectancy of patients with chronic myeloid leukemia (CML). Patients are diagnosed with CML at younger ages, and patients treated for CML may become pregnant or choose to breastfeed. The information available to date on the safety of TKIs during pregnancy and lactation and the optimal management of these patients is largely anecdotal, based on personal or small-group experience, and heterogeneous. A panel of interested parties was convened by U.S. Food and Drug Administration to analyze the current data and discuss possible solutions. Possible solutions include prospective data collection, in clinical trials and in routine clinical practice, a more uniform and specific data collection, and greater coordination among involved entities. As patients with cancer are living longer, frequently receiving therapies for extended periods of time (or for life), data on appropriate management of patients through different reproductive phases of life are needed. It is thus time to change our approach for how to study treatment of cancer (including CML) during pregnancy or breastfeeding to develop evidence-based guidelines for safe and effective patient care.
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Lactancia Materna , Desarrollo de Medicamentos , Leucemia Mielógena Crónica BCR-ABL Positiva , Complicaciones Neoplásicas del Embarazo , Inhibidores de Proteínas Quinasas , Humanos , Embarazo , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Femenino , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversosRESUMEN
This study aimed to determine the bacteriological quality and presence of diarrheagenic Escherichia coli pathotypes (DEP) and nontuberculous mycobacteria (NTM) species in 85 packaged ice samples from 12 different states of central Mexico. Three samples had a pH of 9.8 and therefore fell outside of the acceptable range for pH. All samples were positive for aerobic-mesophilic bacteria, with limits ranging from 1 to 3.47 log CFU/mL. In total, 35, 11, and 3 ice samples were positive for total coliforms (TC), fecal coliforms (FC), and E. coli, respectively. In the samples, the TC concentration ranged from <1.1 to >23 MPN/100 mL and from <1.1 to 23 MPN/100 mL for FC and E. coli. In total, 38 (44.7%) ice samples were outside of Mexico's official guidelines. None of the 12 E. coli strains isolated from the three ice samples belonged to DEP. NTM were recovered from 20 ice samples and included M. neoaurum (n = 7), M. porcinum (n = 2), M. flavescens (n = 2), M. fortuitum (n = 1), M. abscessus (n = 1), M. senegalense (n = 1), M. conceptionense (n = 1), and M. sp. (n = 1). In the remaining four samples, two NTM were isolated simultaneously. Thus, we recommend that producers should evaluate the microbiological quality of purified water used as a raw material as well as that of the final product, the ice should be packed in thick bags to avoid stretching and tearing during transportation or storage to prevent environmental contamination of ice, personnel involved in the production, and handling of ice should be trained in relative hygiene matters and how ice-machines should be cleaned and disinfected and the implementation of hazard analysis and critical control points must be applied throughout the chain of production. Finally, regular inspection by the authorities is also of great importance. These recommendations can be applied in different countries with low microbiological quality packaged ice.
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Hielo , Micobacterias no Tuberculosas , México , Micobacterias no Tuberculosas/aislamiento & purificación , Humanos , Recuento de Colonia Microbiana , Microbiología de Alimentos , Escherichia coli/aislamiento & purificación , Embalaje de Alimentos , Contaminación de Alimentos/análisisRESUMEN
No-take marine protected areas (MPAs) can mitigate the effects of overfishing, climate change and habitat degradation, which are leading causes of an unprecedented global biodiversity crisis. However, assessing the effectiveness of MPAs, especially in remote oceanic islands, can be logistically challenging and often restricted to relatively shallow and accessible environments. Here, we used a long-term dataset (2010-2019) collected by the DeepSee submersible of the Undersea Hunter Group that operates in Isla del Coco National Park, Costa Rica, to (1) determine the frequency of occurrence of elasmobranch species at two depth intervals (50-100 m; 300-400 m), and (2) investigate temporal trends in the occurrence of common elasmobranch species between 2010 and 2019, as well as potential drivers of the observed changes. Overall, we observed 17 elasmobranch species, 15 of which were recorded on shallow dives (50-100 m) and 11 on deep dives (300-400 m). We found a decreasing trend in the probability of occurrence of Carcharhinus falciformis over time (2010-2019), while other species (e.g. Taeniurops meyeni, Sphyrna lewini, Carcharhinus galapagensis, Triaenodon obesus, and Galeocerdo cuvier) showed an increasing trend. Our study suggests that some species like S. lewini may be shifting their distributions towards deeper waters in response to ocean warming but may also be sensitive to low oxygen levels at greater depths. These findings highlight the need for regional 3D environmental information and long-term deepwater surveys to understand the extent of shark and ray population declines in the ETP and other regions, as most fishery-independent surveys from data-poor countries have been limited to relatively shallow waters.
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Biodiversidad , Elasmobranquios , Animales , Océano Pacífico , Conservación de los Recursos Naturales , Ecosistema , Cambio Climático , Costa Rica , IslasRESUMEN
There has been very limited investigation regarding the genetic diversity of Mycobacterium tuberculosis (MTb) strains isolated from human immunodeficiency virus (HIV)-infected patients in Mexico. In this study, we isolated 93 MTb strains from pulmonary and extrapulmonary samples of HIV-infected patients treated in a public hospital in Mexico City to evaluate the genetic diversity using spoligotyping and mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) typing (based on 24 loci). The cohort comprised 80 male and 13 female individuals. There was a positive correlation between a high HIV viral load (>100,000 copies) and extrapulmonary tuberculosis (TB) (r = 0.306, p = 0.008). Lineage 4 was the most frequent lineage (79 strains). In this lineage, we found the H clade (n = 24), including the Haarlem, H3, and H1 families; the T clade (n = 22), including T1 and T2; the X clade (n = 15), including X1 and X3; the LAM clade (n = 14), including LAM1, LAM2, LAM3, LAM6, and LAM9; the S clade (n = 2); Uganda (n = 1); and Ghana (n = 1). We also found 12 strains in the EAI clade belonging to lineage 1, including the EAI2-Manila and EAI5 families. Interestingly, we identified one strain belonging to the Beijing family, which is part of lineage 2. One strain could not be identified. This study reports high genetic diversity among MTb strains, highlighting the need for a molecular epidemiological surveillance system that can help to monitor the spread of these strains, leading to more appropriate measures for TB control in HIV-infected patients.
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Early molecular response (EMR) at 3 months is predictive of improved overall survival (OS) and progression-free survival (PFS) in patients with chronic myeloid leukemia in the chronic phase (CML-CP). Although about one-third of patients treated with first-line imatinib do not achieve EMR, long-term OS and PFS are still observed in most patients. DASCERN (NCT01593254) is a prospective, phase IIb, randomized trial evaluating a switch to dasatinib in patients who have not achieved EMR after 3 months of treatment with first-line imatinib. Early analysis demonstrated an improved major molecular response (MMR) rate at 12 months with dasatinib versus imatinib (29% vs. 13%, P=0.005). Here, we report results from the final 5-year follow-up. In total, 174 patients were randomized to dasatinib and 86 to remain on imatinib. Forty-six (53%) patients who remained on imatinib but subsequently experienced failure were allowed to cross over to dasatinib per protocol. At a minimum follow-up of 60 months, the cumulative MMR rate was significantly higher in patients randomized to dasatinib versus imatinib (77% vs. 44%, P.
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INTRODUCTION: Recurrent mutations in isocitrate dehydrogenase 1 (mIDH1) occur in about 7% to 14% of all cases of acute myeloid leukemia (AML). The discovery of targetable mutations in AML, including IDH mutations, expanded the therapeutic landscape of AML and led to the development of targeted agents. Despite significant advances in current treatment options, remission and overall survival rates remain suboptimal. The IDH1 inhibitor, olutasidenib, demonstrated encouraging safety and clinical benefits as monotherapy in patients with relapsed or refractory (R/R) mIDH1 AML. AREAS COVERED: This review outlines the olutasidenib drug profile and summarizes key safety and efficacy data, focusing on the 150 mg twice daily dose from the pivotal registrational cohort of the phase 2 trial that formed the basis for the US Food and Drug Administration approval of olutasidenib in patients with R/R AML with a susceptible IDH1 mutation. EXPERT OPINION: Olutasidenib offers patients with R/R mIDH1 AML a new treatment option, with improved complete remission and a longer duration of response than other targeted mIDH1 treatment options. Olutasidenib provided clinical benefit with a manageable safety profile. Additional analyses to further characterize the safety and efficacy of olutasidenib in frontline and R/R settings as monotherapy and as combination therapy are ongoing.
Olutasidenib is an oral prescription medication for patients diagnosed with acute myeloid leukemia (AML) with a specific mutation in the isocitrate dehydrogenase 1 (IDH1) gene. The US FDA approved olutasidenib at a dose of 150 mg twice a day for use as stand-alone (monotherapy) treatment in patients with IDH1-mutated AML whose disease has come back or has not improved after previous treatment(s). Olutasidenib is not traditional chemotherapy; it is a targeted treatment called an IDH1 inhibitor, which blocks IDH1 when it has been altered (mutated). These alterations happen in some patients, and when they do, the products of these alterations can lead to leukemia. By blocking mutated IDH1, the body can resume normal blood cell production and functioning. In studies, response to olutasidenib was measured by the number of people who went into remission. Complete remission (CR) means there is no sign of cancer and laboratory values are normal. Complete remission with partial hematologic recovery (CRh) means there is no sign of cancer, but some lab values do not reach normal levels. Thirty-five percent of people taking olutasidenib achieved CR or CRh and stayed in remission for 25.9 months. About 14% of patients who did not achieve remission also experienced some improvement in symptoms. The most common side effects in studies were nausea, feeling tired, fever, constipation, diarrhea, abnormal liver function tests, and changes in certain blood tests. Serious side effects included liver problems and differentiation syndrome, which is a potentially life-threatening situation that can occur when blood cells mature too quickly. Olutasidenib is also being studied in patients with IDH1 mutated AML who have never been treated before and in combination with a chemotherapy medication called azacitidine.
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Isocitrato Deshidrogenasa , Leucemia Mieloide Aguda , Mutación , Humanos , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/antagonistas & inhibidores , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos , Piridinas/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Recurrencia , Resultado del TratamientoRESUMEN
Asciminib targets the BCR::ABL1 myristoyl pocket, maintaining activity against BCR::ABL1T315I, which is resistant to most approved adenosine triphosphate-competitive tyrosine kinase inhibitors. We report updated phase I results (NCT02081378) assessing safety/tolerability and antileukemic activity of asciminib monotherapy 200 mg twice daily in 48 heavily pretreated patients with T315I-mutated chronic-phase chronic myeloid leukemia (CML-CP; data cutoff: January 6, 2021). With 2 years' median exposure, 56.3% of patients continued receiving asciminib. Overall, 62.2% of evaluable patients achieved BCR::ABL1 ≤1% on the International Scale (IS); 47.6% and 81.3% of ponatinib-pretreated and -naive patients, respectively, achieved BCR::ABL1IS ≤1%. Of 45 evaluable patients, 48.9% achieved a major molecular response (MMR, BCR::ABL1IS ≤0.1%), including 34.6% and 68.4% of ponatinib-pretreated and -naive patients, respectively. MMR was maintained until data cutoff in 19 of 22 patients who achieved it. The most common grade ≥3 adverse events (AEs) included increased lipase level (18.8%) and thrombocytopenia (14.6%). Five (10.4%) patients experienced AEs leading to discontinuation, including 2 who discontinued asciminib and died due to COVID-19; these were the only deaths reported. These results show asciminib's effectiveness, including in almost 50% of ponatinib pretreated patients, and confirm its risk-benefit profile, supporting its use as a treatment option for T315I-mutated CML-CP.
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Proteínas de Fusión bcr-abl , Leucemia Mieloide de Fase Crónica , Mutación , Inhibidores de Proteínas Quinasas , Humanos , Masculino , Persona de Mediana Edad , Femenino , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Anciano , Adulto , Estudios de Seguimiento , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/genética , Proteínas de Fusión bcr-abl/genética , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Anciano de 80 o más Años , Adulto Joven , Resistencia a Antineoplásicos , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Niacinamida/análogos & derivados , PirazolesRESUMEN
BACKGROUND: Patients with newly diagnosed chronic myeloid leukemia (CML) need long-term therapy with high efficacy and safety. Asciminib, a BCR::ABL1 inhibitor specifically targeting the ABL myristoyl pocket, may offer better efficacy and safety and fewer side effects than currently available frontline ATP-competitive tyrosine kinase inhibitors (TKIs). METHODS: In a phase 3 trial, patients with newly diagnosed CML were randomly assigned in a 1:1 ratio to receive either asciminib (80 mg once daily) or an investigator-selected TKI, with randomization stratified by European Treatment and Outcome Study long-term survival score category (low, intermediate, or high risk) and by TKI selected by investigators before randomization (including imatinib and second-generation TKIs). The primary end points were major molecular response (defined as BCR::ABL1 transcript levels ≤0.1% on the International Scale [IS]) at week 48, for comparisons between asciminib and investigator-selected TKIs and between asciminib and investigator-selected TKIs in the prerandomization-selected imatinib stratum. RESULTS: A total of 201 patients were assigned to receive asciminib and 204 to receive investigator-selected TKIs. The median follow-up was 16.3 months in the asciminib group and 15.7 months in the investigator-selected TKI group. A major molecular response at week 48 occurred in 67.7% of patients in the asciminib group, as compared with 49.0% in the investigator-selected TKI group (difference, 18.9 percentage points; 95% confidence interval [CI], 9.6 to 28.2; adjusted two-sided P<0.001]), and in 69.3% of patients in the asciminib group as compared with 40.2% in the imatinib group within the imatinib stratum (difference, 29.6 percentage points; 95% CI, 16.9 to 42.2; adjusted two-sided P<0.001). The percentage of patients with a major molecular response at week 48 was 66.0% with asciminib and 57.8% with TKIs in the second-generation TKI stratum (difference, 8.2 percentage points; 95% CI, -5.1 to 21.5). Adverse events of grade 3 or higher and events leading to discontinuation of the trial regimen were less frequent with asciminib (38.0% and 4.5%, respectively) than with imatinib (44.4% and 11.1%) and second-generation TKIs (54.9% and 9.8%). CONCLUSIONS: In this trial comparing asciminib with investigator-selected TKIs and imatinib, asciminib showed superior efficacy and a favorable safety profile in patients with newly diagnosed chronic-phase CML. Direct comparison between asciminib and second-generation TKIs was not a primary objective. (Funded by Novartis; ASC4FIRST ClinicalTrials.gov number, NCT04971226).
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Antineoplásicos , Proteínas de Fusión bcr-abl , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva , Pirazoles , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Proteínas de Fusión bcr-abl/genética , Mesilato de Imatinib/uso terapéutico , Mesilato de Imatinib/efectos adversos , Estimación de Kaplan-Meier , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Niacinamida/análogos & derivados , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , /efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Ponatinib is a third-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) with robust activity in Philadelphia chromosome-positive leukemias. Herein, we report the long-term follow-up of the phase 2 trial of ponatinib in chronic myeloid leukemia in chronic phase. METHODS: Patients received ponatinib 30 to 45 mg/day. The primary end point was the rate of 6-month complete cytogenetic response (CCyR). The study was held in June 2014 because of the risk of cardiovascular toxicity, requiring patients to change TKI. RESULTS: Fifty-one patients were treated with ponatinib (median dose, 45 mg/day). Median age was 48 years (range, 21-75); 30 (59%) had baseline cardiovascular comorbidities. Median treatment duration was 13 months (range, 2-25). Fourteen patients (28%) discontinued ponatinib because of toxicities, 36 (71%) after the Food and Drug Administration warning/study closure, and one for noncompliance. Dasatinib was the most frequently chosen second-line TKI (n = 34; 66%). Among 46 patients evaluable at 6 months, 44 (96%) achieved CCyR, 37 (80%) major molecular response, 28 (61%) MR4, and 21 (46%) MR4.5. The cumulative 6-month rates of CCyR, major molecular response, MR4, and MR4.5 were 96%, 78%, 50%, and 36%, respectively. Durable MR4 ≥24 or ≥60 months was observed in 67% and 51% of patients, respectively. The 24-month event-free survival rate was 97%. After a median follow-up of 128 months, the 10-year overall survival rate was 90%. Eight patients (16%) had serious grade 2 to 3 cardiovascular adverse events, leading to permanent discontinuation in five (10%). CONCLUSION: Ponatinib yielded high cytogenetic and molecular responses in newly diagnosed chronic myeloid leukemia in chronic phase. Its use in the frontline setting is hindered by arterio-/vaso-occlusive and other severe toxicities.
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Imidazoles , Leucemia Mielógena Crónica BCR-ABL Positiva , Inhibidores de Proteínas Quinasas , Piridazinas , Humanos , Piridazinas/efectos adversos , Piridazinas/uso terapéutico , Piridazinas/administración & dosificación , Imidazoles/efectos adversos , Imidazoles/uso terapéutico , Imidazoles/administración & dosificación , Persona de Mediana Edad , Adulto , Masculino , Femenino , Anciano , Adulto Joven , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Estudios de Seguimiento , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Proteínas de Fusión bcr-abl/genética , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Resultado del Tratamiento , Dasatinib/efectos adversos , Dasatinib/uso terapéutico , Dasatinib/administración & dosificación , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversosAsunto(s)
Anemia , Mielofibrosis Primaria , Humanos , Mielofibrosis Primaria/tratamiento farmacológico , Mielofibrosis Primaria/complicaciones , Anemia/tratamiento farmacológico , Anemia/etiología , Femenino , Proteínas Recombinantes de Fusión/uso terapéutico , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , AncianoRESUMEN
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.
RESUMEN
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.