RESUMEN
Our understanding of sex and gender evolves. We asked scientists about their work and the future of sex and gender research. They discuss, among other things, interdisciplinary collaboration, moving beyond binary conceptualizations, accounting for intersecting factors, reproductive strategies, expanding research on sex-related differences, and sex's dynamic nature.
Asunto(s)
Investigación Biomédica , Identidad de Género , Sexo , Femenino , Humanos , Masculino , Caracteres SexualesRESUMEN
We report 2 autochthonous feline thelaziosis cases caused by the eyeworm Thelazia callipaeda and discuss the spread among dogs in the northeastern United States. Phylogenetic analysis suggests the parasite was introduced from Europe. Adopting a One Health approach is needed to limit further spread of T. callipaeda eyeworms in North America.
Asunto(s)
Enfermedades de los Gatos , Enfermedades de los Perros , Thelazioidea , Gatos , Animales , Perros , Enfermedades de los Gatos/epidemiología , Filogenia , Enfermedades de los Perros/epidemiología , New England , Loa , Thelazioidea/genéticaRESUMEN
BACKGROUND: The Financial Incentives for Weight Reduction (FIReWoRk) clinical trial showed that financial incentive weight-loss strategies designed using behavioral economics were more effective than provision of weight-management resources only. We now evaluate cost-effectiveness. METHODS: Cost-effectiveness analysis of a multisite randomized trial enrolling 668 participants with obesity living in low-income neighborhoods. Participants were randomized to (1) goal-directed incentives (targeting behavioral goals), (2) outcome-based incentives (targeting weight-loss), and (3) resources only, which were provided to all participants and included a 1-year commercial weight-loss program membership, wearable activity monitor, food journal, and digital scale. We assessed program costs, time costs, quality of life, weight, and incremental cost-effectiveness in dollars-per-kilogram lost. RESULTS: Mean program costs at 12 months, based on weight loss program attendance, physical activity participation, food diary use, self-monitoring of weight, and incentive payments was $1271 in the goal-directed group, $1194 in the outcome-based group, and $834 in the resources-only group (difference, $437 [95% CI, 398 to 462] and $360 [95% CI, 341-363] for goal-directed or outcome-based vs resources-only, respectively; difference, $77 [95% CI, 58-130] for goal-directed vs outcome-based group). Quality of life did not differ significantly between the groups, but weight loss was substantially greater in the incentive groups (difference, 2.34 kg [95% CI, 0.53-4.14] and 1.79 kg [95% CI, -0.14 to 3.72] for goal-directed or outcome-based vs resources only, respectively; difference, 0.54 kg [95% CI, -1.29 to 2.38] for goal-directed vs outcome-based). Cost-effectiveness of incentive strategies based on program costs was $189/kg lost in the goal-directed group (95% CI, $124/kg to $383/kg) and $186/kg lost in the outcome-based group (95% CI, $113/kg to $530/kg). CONCLUSIONS: Goal-directed and outcome-based financial incentives were cost-effective strategies for helping low-income individuals with obesity lose weight. Their incremental cost per kilogram lost were comparable to other weight loss interventions.
Asunto(s)
Motivación , Programas de Reducción de Peso , Humanos , Análisis Costo-Beneficio , Análisis de Costo-Efectividad , Objetivos , Calidad de Vida , Obesidad/terapiaRESUMEN
BACKGROUND: Rural patients suffer higher incidence of and mortality from colorectal cancer. Ensuring high-quality screening is essential to address these disparities. OBJECTIVE: To investigate whether socioecological determinants of health are associated with colonoscopy quality in rural Alabama. DESIGN: Retrospective review. SETTING: Data across three rural hospitals in Alabama from August 2021 to July 2023. PATIENTS: We included adults (≥18 years) who underwent screening or diagnostic colonoscopy and completed a validated survey that measures socioecological determinants of health. MAIN OUTCOME MEASURES: Primary outcomes included bowel preparation quality, cecal intubation, and adenoma detection rate. We linked th e survey responses to these quality metrics to identify factors associated with outcomes. Analyses included the χ 2, Fisher's Exact and Kruskal-Wallis Rank sum tests, with p < 0.05 considered statistically significant. RESULTS: The 84 patients surveyed were 66.7% male, 50.0% Black, and had a median age of 64 years. Optimal bowel preparation was present in 88.0%, 89.3% had successful cecal intubations, and overall adenoma detection rate was 45.8%. Patients with suboptimal bowel preparation described lower rates of internet access (60.0% vs. 87.4%, p < 0.05), more difficulty understanding written information (30.0% vs. 1.4%, p < 0.05) and lacked a sense of responsibility for their health (30.0% vs. 51.4%, p < 0.05) compared to those having optimal bowel preparation. Those with unsuccessful cecal intubations had lower physician-trust (55.6% vs. 73.3%, p < 0.05), while patients with successful cecal intubations were more confident in preventing health-related problems (53.3% vs. 33.3%, p < 0.05) and had a more supportive social environment (72.0% vs. 66.7%, p < 0.05). LIMITATIONS: Retrospective design and small sample size limiting multivariable analyses. CONCLUSION: In rural Alabama, health literacy, internet access, and physician-trust were associated with low-quality colonoscopy, while a higher patient sense of responsibility and a supportive social environment was associated with higher-quality metrics. These findings identify potential targets for improving colonoscopy quality in rural settings. See Video Abstract.
RESUMEN
Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) treatment are of interest in oncology due to ease of administration and lack of need for therapeutic monitoring compared to other anticoagulants. Data supporting their use in patients with hematologic malignancies post-hematopoietic stem cell transplant (HCT) are limited. The purpose of the study is to characterize DOAC use in HCT patients. This multicenter, retrospective cohort analysis included allogeneic and autologous HCT recipients. The primary outcome was major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB)/minor bleeding and VTE recurrence. Of 126 patients, 91 (72.2%) patients received an autologous HCT, and 35 (27.8%) patients received an allo-HCT. No major bleeding occurred in either transplant recipient groups. In autologous HCT recipients, CRNMB/minor bleeding occurred in four (4.4%) patients and VTE recurrence occurred in one (1.1%) patient. For allogeneic HCT recipients, CRNMB/minor bleeding occurred in five (14.3%) patients and VTE recurrence occurred in two (5.7%) patients. For patients that experienced a CRNMB, five (100%) of the allogeneic HCT and two (50%) of the autologous HCT recipients were thrombocytopenic at the time of bleeding. Only 38.5% of patients who experienced a drug-drug interaction requiring DOAC dose adjustment received the appropriate dose adjustment. DOACs were associated with low rates of recurrent VTE and no major bleeding events, similar to published data on DOAC use in the general cancer patient population. This suggests that DOACs may be safe therapeutic options with proactive management of drug interactions and careful monitoring for bleeding events, especially in the allogeneic HCT population where minor bleeding rates were slightly higher.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Tromboembolia Venosa , Adulto , Humanos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/inducido químicamente , Estudios Retrospectivos , Receptores de Trasplantes , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Administración Oral , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
BACKGROUND: The University of California's Diabetes Prevention Program (UC DPP) Initiative was implemented systemwide to address diabetes and obesity risk on all 10 campuses. As little is known about implementing lifestyle change programs in university settings, we examined implementation partners' (i.e., UC DPP leaders and campus leads) perceptions of factors influencing program success on UC campuses. METHODS: We conducted qualitative interviews with UC DPP leaders and campus leads to examine challenges and opportunities with university-based DPP delivery models. Interviews were recorded, professionally transcribed, and reviewed in detail by the research team. Transcripts were analyzed using rapid qualitative analysis (RQA). The study was approved by the UCLA Institutional Review Board. All implementation partners provided verbal informed consent. RESULTS: Twenty-six implementation partners (8 UC DPP leaders and 18 campus leads) completed interviews in 2021. Seven themes were identified as critical for implementation, including (1) marketing and recruitment (i.e., market and recruit broadly through established channels as well as target at-risk populations); (2) enrollment (i.e., offer the program during convenient times and let participants know what to expect); (3) use an adaptable, evidence-based program; (4) secure funding for the program, participants, lifestyle coaches, and space; (5) hire experienced and dedicated staff and lifestyle coaches; (6) ensure leadership support; and (7) utilize campus linkages and resources. Perceptions of challenges faced with respect to these themes are also described. CONCLUSIONS: This is one of the first studies to examine the challenges and opportunities of delivering an intensive lifestyle change program across 10 university sites. Understanding factors that enhance success of university-based diabetes prevention programs can facilitate UC DPP efforts and help inform delivery strategies of health and wellness programs across other university settings more broadly.
Asunto(s)
Investigación Cualitativa , Humanos , California , Universidades , Promoción de la Salud/organización & administración , Promoción de la Salud/métodos , Diabetes Mellitus Tipo 2/prevención & control , Evaluación de Programas y Proyectos de Salud , Entrevistas como Asunto , Desarrollo de Programa , Obesidad/prevención & controlRESUMEN
Historically, atrocities against Black, Indigenous, and Women of Color's (BIWoC) reproductive rights have been committed and continue to take place in contemporary society. The atrocities against BIWoC have been fueled by White supremacy ideology of the "desirable race" and colonial views toward controlling poverty and population growth, particularly that of "undesirable" races and ethnicities. Grounded in Critical Race Theory, this paper aims to provide a critical analysis of historical and contemporary violations of BIWoC reproductive rights; discuss interventions based on empowerment and advocacy principles designed to promote women's reproductive justice; and discuss implications for future research, action, and policy from the lenses of Critical Race Theory and Community Psychology. This paper contributes to the special issue by critically analyzing historical and contemporary racism and colonialism against BIWoC, discussing implications for future research and practice, and making policy recommendations.
Asunto(s)
Negro o Afroamericano , Justicia Social , Femenino , Humanos , Clorhexidina , Colonialismo , Etnicidad , Pigmentación de la Piel , Pueblos IndígenasRESUMEN
An individual's telomere length early in life may reflect or contribute to key life-history processes sensitive to environmental variation. Yet, the relative importance of genetic and environmental factors in shaping early-life telomere length is not well understood as it requires samples collected from multiple generations with known developmental histories. We used a confirmed pedigree and conducted an animal model analysis of telomere lengths obtained from nestling house sparrows (Passer domesticus) sampled over a span of 22 years. We found significant additive genetic variation for early-life telomere length, but it comprised a small proportion (9%) of the total biological variation. Three sources of environmental variation were important: among cohorts, among-breeding attempts within years, and among nestmates. The magnitude of variation among breeding attempts and among nestmates also differed by cohort, suggesting that interactive effects of environmental factors across time or spatial scales were important, yet we were unable to identify the specific causes of these interactions. The mean amount of precipitation during the breeding season positively predicted telomere length, but neither weather during a given breeding attempt nor date in the breeding season contributed to an offspring's telomere length. At the level of individual nestlings, offspring sex, size and mass at 10 days of age also did not predict telomere length. Environmental effects appear especially important in shaping early-life telomere length in some species, and more focus on how environmental factors that interact across scales may help to explain some of the variation observed among studies.
Asunto(s)
Acortamiento del Telómero , Telómero , Humanos , Animales , Acortamiento del Telómero/genética , Telómero/genética , Estaciones del Año , LongevidadRESUMEN
BACKGROUND: For patients with multiple myeloma (MM) who have undergone autologous stem cell transplant (auto-SCT), the immunomodulatory agent lenalidomide is a first-line option for maintenance therapy. Because longer durations of lenalidomide maintenance are associated with improved survival, identifying strategies to avoid premature cessation of maintenance is an important priority in the post-transplant setting. OBJECTIVES: The primary objective of this analysis was to identify specific clinical predictors of lenalidomide treatment duration that could guide optimal medication management. Key secondary objectives included predictors of intolerable toxicity, rationale for lenalidomide dose reduction/discontinuation, and characterization of dose adjustments. STUDY DESIGN: This retrospective, multi-center cohort study included adults with MM who underwent auto-SCT and initiated maintenance lenalidomide between 01/01/2012 and 02/28/2021. Variables assessed as potential predictors of maintenance duration or intolerable toxicity included age, body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status at time of auto-SCT, renal function, initial lenalidomide dose, use of combination maintenance therapy, and cytogenetic risk category. RESULTS: Among 299 patients included, the median age at time of auto-SCT was 62 years (range 30-77). The majority of patients had standard-risk cytogenetics (64%) and an ECOG performance status of 0 or 1 (72%). In the overall population, the median duration of maintenance was 1.3 years (range 0.3-8.6 years). The median initial dose of lenalidomide was 10â mg daily (range 2.5-25â mg). During the study period, 35% of patients had a dose reduction due to toxicity, 21% stopped lenalidomide due to disease progression, and 19% stopped due to toxicity. Multivariate linear regression analyses did not identify any significant predictors of lenalidomide duration or discontinuation due to intolerable toxicity. The most frequently reported toxicities leading to discontinuation were cytopenias, rash, and fatigue. CONCLUSION: This analysis did not identify any significant risk factors to predict the duration of lenalidomide maintenance or discontinuation for toxicity following auto-SCT in patients with MM. While limited by the retrospective design and relatively small sample size, our findings suggest that a priori lenalidomide dose reductions based on patient co-morbidities or performance status may not substantially affect the duration of lenalidomide maintenance.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Adulto , Humanos , Persona de Mediana Edad , Anciano , Mieloma Múltiple/tratamiento farmacológico , Lenalidomida/uso terapéutico , Estudios Retrospectivos , Estudios de Cohortes , Supervivencia sin Enfermedad , Trasplante Autólogo , Trasplante de Células Madre , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
OBJECTIVE: Antibiotic stewardship should be an essential component of neonatology training as neonatal intensive care units (NICU) have unique stewardship needs. Our aim was to assess neonatology fellowship trainees' knowledge, attitudes, and perceptions about antibiotic stewardship to inform sustainable curriculum development. STUDY DESIGN: We distributed an electronic survey to neonatology fellows in the United States over 4 months (January-April 2018) via Accreditation Council for Graduate Medical Education program directors. RESULTS: Of 99 programs in the United States with an estimated 700 fellows, 159 (23%) fellows from 52 training programs (53%) responded to the survey and 139 (87%) provided analyzed responses. Majority of respondents were training in southern (59; 42%) and northeastern (43; 31%) regions and were equally spread across all 3 years of training. One hundred (72%) respondents reported an antibiotic stewardship program (ASP) in their institution. While 86% (120/139) were able to identify the components of an ASP, 59% (82/139) either did not or were unsure if they had received antibiotic stewardship training during fellowship.Furthermore, while answering case studies, 124 (89%) respondents identified the optimal antibiotic for methicillin susceptible Staphylococcus aureus (MSSA) infection and 69 (50%) respondents chose appropriate empiric antibiotics for neonatal meningitis. Notably, fellowship training year was not significantly related to the proportion of incorrect knowledge responses (p = 0.40). Most survey respondents (81; 59%) identified small group sessions as the most useful teaching format, while others chose audit and feedback of individual prescribing behavior (52; 38%) and didactic lectures (52; 38%). Finally, ninety-five (69%) respondents preferred trainee-led ASP interventions targeting focal areas such as antifungal and surgical prophylaxis. CONCLUSION: Antibiotic stewardship is a critical part of neonatology training. Neonatology fellows report variation in access to ASP during their training. Fellows prefer dedicated trainee-led interventions and stewardship curriculum taught within small group settings to promote targeted NICU ASP. KEY POINTS: · Most neonatology programs expose trainees to internal or external antibiotic stewardship programs.. · Over half of fellow trainees are unsure about receiving targeted antibiotic stewardship training.. · Most neonatology fellows prefer a trainee-led antibiotic stewardship intervention..
Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos , Neonatología , Recién Nacido , Humanos , Estados Unidos , Conocimientos, Actitudes y Práctica en Salud , Curriculum , Educación de Postgrado en Medicina , Encuestas y Cuestionarios , BecasRESUMEN
Onychophora ("velvet worms") are charismatic soil invertebrates known for their status as a "living fossil," their phylogenetic affiliation to arthropods, and their distinctive biogeographic patterns. However, several aspects of their internal phylogenetic relationships remain unresolved, limiting our understanding of the group's evolutionary history, particularly with regard to changes in reproductive mode and dispersal ability. To address these gaps, we used RNA sequencing and phylogenomic analysis of transcriptomes to reconstruct the evolutionary relationships and infer divergence times within the phylum. We recovered a fully resolved and well-supported phylogeny for the circum-Antarctic family Peripatopsidae, which retains signals of Gondwanan vicariance and showcases the evolutionary lability of reproductive mode in the family. Within the Neotropical clade of Peripatidae, though, we found that amino acid-translated sequence data masked nearly all phylogenetic signal, resulting in highly unstable and poorly supported relationships. Analyses using nucleotide sequence data were able to resolve many more relationships, though we still saw discordant phylogenetic signal between genes, probably indicative of a rapid, mid-Cretaceous radiation in the group. Finally, we hypothesize that the unique reproductive mode of placentotrophic viviparity found in all Neotropical peripatids may have facilitated the multiple inferred instances of over-water dispersal and establishment on oceanic islands.
Asunto(s)
Artrópodos , Evolución Biológica , Animales , Fósiles , Invertebrados/genética , FilogeniaRESUMEN
We investigated the incidence of invasive fungal infections (IFIs) and other infectious complications in patients receiving venetoclax and hypomethylating agent therapy for acute myeloid leukaemia (AML). This retrospective, multicentre cohort study included adult patients with AML who received at least one cycle of venetoclax and either azacitidine or decitabine between January 2016 and August 2020. The primary outcome was the incidence of probable or confirmed IFI. Secondary outcomes included antifungal prophylaxis prescribing patterns, incidence of bacterial infections, and incidence of neutropenic fever hospital admissions. Among 235 patients, the incidence of probable or confirmed IFI was 5.1%. IFI incidence did not differ significantly according to age, antifungal prophylaxis use, or disease status. In the subgroup of patients with probable or confirmed IFIs, six (50%) were receiving antifungal prophylaxis at the time of infection. The overall incidence of developing at least one bacterial infection was 33.6% and 127 (54%) patients had at least one hospital admission for febrile neutropenia. This study demonstrated an overall low risk of developing probable or confirmed IFI as well as a notable percentage of documented bacterial infections and hospital admissions due to neutropenic fever.
Asunto(s)
Infecciones Fúngicas Invasoras , Leucemia Mieloide Aguda , Adulto , Antifúngicos/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes , Estudios de Cohortes , Humanos , Infecciones Fúngicas Invasoras/epidemiología , Leucemia Mieloide Aguda/complicaciones , Estudios Retrospectivos , SulfonamidasRESUMEN
Parental stress often has long-term consequences for offspring. However, the mechanisms underlying these effects and how they are shaped by conditions offspring subsequently experience are poorly understood. Telomeres, which often shorten in response to stress and predict longevity, may contribute to, and/or reflect these cross-generational effects. Traditionally, parental stress is expected to have negative effects on offspring telomeres, but experimental studies in captive animals suggest that these effects may depend on the subsequent conditions that offspring experience. Yet, the degree to which parental stress influences and interacts with stress experienced by offspring to affect offspring telomeres and survival in free-living organisms is unknown. To assess this, we experimentally manipulated the stress exposure of free-living parent and offspring house sparrows (Passer domesticus). We found a weak, initial, negative effect of parental stress on offspring telomeres, but this effect was no longer evident at the end of post-natal development. Instead, the effects of parental stress depended on the natural sources of stress that offspring experienced during post-natal development whereby some outcomes were improved under more stressful rearing conditions. Thus, the effects of parental stress on offspring telomeres and survival are context-dependent and may involve compensatory mechanisms of potential benefit under some circumstances.
Asunto(s)
Gorriones , Animales , Longevidad , Gorriones/fisiología , TelómeroRESUMEN
Social status is a critical factor determining health outcomes in human and nonhuman social species. In social hierarchies with reproductive skew, individuals compete to monopolize resources and increase mating opportunities. This can come at a significant energetic cost leading to trade-offs between different physiological systems. In particular, changes in energetic investment in the immune system can have significant short and long-term effects on fitness and health. We have previously found that dominant alpha male mice living in social hierarchies have increased metabolic demands related to territorial defense. In this study, we tested the hypothesis that high-ranking male mice favor adaptive immunity, while subordinate mice show higher investment in innate immunity. We housed 12 groups of 10 outbred CD-1 male mice in a social housing system. All formed linear social hierarchies and subordinate mice had higher concentrations of plasma corticosterone (CORT) than alpha males. This difference was heightened in highly despotic hierarchies. Using flow cytometry, we found that dominant status was associated with a significant shift in immunophenotypes towards favoring adaptive versus innate immunity. Using Tag-Seq to profile hepatic and splenic transcriptomes of alpha and subordinate males, we identified genes that regulate metabolic and immune defense pathways that are associated with status and/or CORT concentration. In the liver, dominant animals showed a relatively higher expression of specific genes involved in major urinary production and catabolic processes, whereas subordinate animals showed relatively higher expression of genes promoting biosynthetic processes, wound healing, and proinflammatory responses. In spleen, subordinate mice showed relatively higher expression of genes facilitating oxidative phosphorylation and DNA repair and CORT was negatively associated with genes involved in lymphocyte proliferation and activation. Together, our findings suggest that dominant and subordinate animals adaptively shift immune profiles and peripheral gene expression to match their contextual needs.
Asunto(s)
Jerarquia Social , Predominio Social , Animales , Corticosterona , Masculino , Ratones , TranscriptomaRESUMEN
Females and males often exhibit different survival in nature, and it has been hypothesized that sex chromosomes may play a role in driving differential survival rates. For instance, the Y chromosome in mammals and the W chromosome in birds are often degenerated, with reduced numbers of genes, and loss of the Y chromosome in old men is associated with shorter life expectancy. However, mosaic loss of sex chromosomes has not been investigated in any non-human species. Here, we tested whether mosaic loss of the W chromosome (LOW) occurs with ageing in wild birds as a natural consequence of cellular senescence. Using loci-specific PCR and a target sequencing approach we estimated LOW in both young and adult individuals of two long-lived bird species and showed that the copy number of W chromosomes remains constant across age groups. Our results suggest that LOW is not a consequence of cellular ageing in birds. We concluded that the inheritance of the W chromosome in birds, unlike the Y chromosome in mammals, is more stable.
Asunto(s)
Cromosomas Humanos Y , Evolución Molecular , Animales , Aves/genética , Femenino , Humanos , Masculino , Mamíferos/genética , Mosaicismo , Cromosomas Sexuales/genéticaRESUMEN
Parental age at offspring conception often influences offspring longevity, but the mechanisms underlying this link are poorly understood. One mechanism that may be important is telomeres, highly conserved, repetitive sections of non-coding DNA that form protective caps at chromosome ends and are often positively associated with longevity. Here, the potential pathways by which the age of the parents at the time of conception may impact offspring telomeres are described first, including direct effects on parental gamete telomeres and indirect effects on offspring telomere loss during pre- or post-natal development. Then a surge of recent studies demonstrating the effects of parental age on offspring telomeres in diverse taxa are reviewed. In doing so, important areas for future research and experimental approaches that will enhance the understanding of how and when these effects likely occur are highlighted. It is concluded by considering the potential evolutionary consequences of parental age on offspring telomeres.
Asunto(s)
Longevidad , Telómero , Humanos , Longevidad/genética , Padres , Telómero/genética , Acortamiento del TelómeroRESUMEN
INTRODUCTION: Plasma cell leukemia (PCL) is a rare but aggressive variant of multiple myeloma (MM) with a poor prognosis. Due to the limited number of prospective clinical trials studying PCL, treatment options are often extrapolated from data available for the treatment of MM. Venetoclax has recently demonstrated antimyeloma activity in patients with relapsed/refractory MM carrying the t(11;14) translocation. However, few cases have reported the analogous efficacy of venetoclax in PCL. CASE REPORT: A 64-year-old Caucasian male developed relapsed PCL despite treatment with hyperCD (hyperfractionated cyclophosphamide and dexamethasone) and Dara-KRd (daratumumab, carfilzomib, lenalidomide, dexamethasone). Due to the refractory nature of his disease and the presence of a t(11:14) translocation, the patient was subsequently initiated on venetoclax 400â mg daily and dexamethasone 4â mg once weekly. MANAGEMENT AND OUTCOME: The patient achieved a complete response by International Myeloma Working Group criteria three months after initiating venetoclax-dexamethasone, including a repeat bone marrow biopsy that showed no abnormal plasma cells. He successfully underwent consolidation with melphalan-based autologous stem cell transplantation. He remains disease-free 9 months after venetoclax initiation. DISCUSSION: Combination all-oral therapy with venetoclax and dexamethasone can induce deep hematologic responses in patients with relapsed/refractory PCL carrying the t(11;14) translocation.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia de Células Plasmáticas , Mieloma Múltiple , Humanos , Masculino , Persona de Mediana Edad , Leucemia de Células Plasmáticas/tratamiento farmacológico , Estudios Prospectivos , Dexametasona/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante Autólogo , Mieloma Múltiple/terapiaRESUMEN
INTRODUCTION: Subcutaneous daratumumab is non-inferior to intravenous daratumumab for the treatment of multiple myeloma and significantly reduced incidence of systemic reactions. However, manufacturer for subcutaneous daratumumab has not provided guidance regarding optimal methods for monitoring for hypersensitivity reactions following subcutaneous daratumumab administration. METHODS: A retrospective analysis was performed in two cohorts of patients who received at least two doses of subcutaneous daratumumab for the treatment of plasma cell disorders: patients with previous exposure to intravenous daratumumab (dara-exposed) and patients without history of intravenous daratumumab (dara-naïve). The primary outcome was incidence of systemic and injection-site reactions following first dose of subcutaneous daratumumab. Secondary analysis included time to systemic and injection-site reactions, grading of adverse reaction, and incidence of second systemic reaction. RESULTS: Thirty-one patients were dara-naïve and 49 patients were dara-exposed. Differences in incidence of systemic (dara-naïve: 9.7% vs dara-exposed: 6.1%, p = 0.67) and injection-site reactions (dara-naïve: 12.9% vs dara-exposed: 14.3%, p = 0.99) did not reach statistical significance. Difference in median time to systemic reaction (dara-naïve: 3â h vs dara-exposed: 12â h, p = 0.18) was clinically important but did not reach statistical significance. Median time to injection-site reactions (dara-naïve: 6â h vs dara-exposed: 24â h, p = 0.03) was shorter in the dara-naïve cohort. No clinically meaningful difference was observed for incidence of second systemic reaction. CONCLUSION: Most reactions were mild and did not require medical intervention. Following first subcutaneous daratumumab dose, monitoring for 3â h for dara-naïve patients and no monitoring time for dara-exposed patients for hypersensitivity reactions may be a safe and reasonable practice.
Asunto(s)
Anticuerpos Monoclonales , Mieloma Múltiple , Humanos , Estudios Retrospectivos , Anticuerpos Monoclonales/efectos adversos , Mieloma Múltiple/tratamiento farmacológico , Inyecciones Subcutáneas , Atención AmbulatoriaRESUMEN
Social monogamy, typically characterized by the formation of a pair bond, increased territorial defense, and often biparental care, has independently evolved multiple times in animals. Despite the independent evolutionary origins of monogamous mating systems, several homologous brain regions and neuropeptides and their receptors have been shown to play a conserved role in regulating social affiliation and parental care, but little is known about the neuromolecular mechanisms underlying monogamy on a genomic scale. Here, we compare neural transcriptomes of reproductive males in monogamous and nonmonogamous species pairs of Peromyscus mice, Microtus voles, parid songbirds, dendrobatid frogs, and Xenotilapia species of cichlid fishes. We find that, while evolutionary divergence time between species or clades did not explain gene expression similarity, characteristics of the mating system correlated with neural gene expression patterns, and neural gene expression varied concordantly across vertebrates when species transition to monogamy. Our study provides evidence of a universal transcriptomic mechanism underlying the evolution of monogamy in vertebrates.
Asunto(s)
Transcriptoma/genética , Vertebrados/genética , Animales , Anuros/genética , Arvicolinae/genética , Encéfalo/fisiología , Cíclidos/genética , Expresión Génica/genética , Masculino , Ratones , Apareamiento , Peromyscus/genética , Filogenia , Reproducción/genética , Conducta Sexual Animal/fisiología , Pájaros Cantores/genética , Especificidad de la EspecieRESUMEN
INTRODUCTION: Some patients experience ongoing sequelae after discharge, including rehospitalization; therefore, outcomes following COVID-19 hospitalization are of continued interest. We examined readmissions within 90 days of hospital discharge for veterans hospitalized with COVID-19 during the first 10 months of the pandemic in the US. METHODS: Veterans hospitalized with COVID-19 at a Veterans Health Administration (VA) hospital from March 1, 2020, through December 31, 2020 were followed for 90 days after discharge to determine readmission rates. RESULTS: Of 20,414 veterans hospitalized with COVID-19 during this time period, 13% (n = 2,643) died in the hospital. Among survivors (n = 17,771), 16% (n = 2,764) were readmitted within 90 days of discharge, with a mean time to readmission of 21.6 days (SD = 21.1). Characteristics of the initial COVID-19 hospitalization associated with readmission included length of stay, mechanical ventilator use, higher comorbidity index score, current smoking, urban residence, discharged against medical advice, and hospitalized from September through December 2020 versus March through August 2020 (all P values <.02). Veterans readmitted from September through December 2020 were more often White, lived in a rural or highly rural area, and had shorter initial hospitalizations than veterans hospitalized earlier in the year. CONCLUSION: Approximately 1 of 6 veterans discharged alive following a COVID-19 hospitalization from March 1 through December 31, 2020, were readmitted within 90 days. The longer the hospital stay, the greater the likelihood of readmission. Readmissions also were more likely when the initial admission required mechanical ventilation, or when the veteran had multiple comorbidities, smoked, or lived in an urban area. COVID-19 hospitalizations were shorter from September through December 2020, suggesting that hospital over-capacity may have resulted in earlier discharges and increased readmissions. Efforts to monitor and provide support for patients discharged in high bed-capacity situations may help avoid readmissions.