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Referential signaling, a complex form of communication in which specific signals are associated with external referents, was once thought to be limited to primates. Recent research has documented referential signaling in several other cooperative taxa, predominantly in kin-based societies. Here, we show that greater anis, communally nesting birds that breed in nonkin groups, give one type of alarm call in response to aerial threats (flying raptors) and another to more general threats (nonaerial predators). Observational data show that anis give these calls in response to different classes of threats, and playback experiments in the field confirmed that the alarm calls alone are sufficient to elicit appropriate behavioral responses even in the absence of an actual threat. Genetic data on a subset of groups confirmed that breeding groups are composed of nonkin, suggesting that referential alarm calls are often given in situations when no genetic relatives are present. These results suggest that complex referential communication can occur in social groups composed of nonrelatives, despite the absence of kin-selected fitness benefits.
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Aves Predatórias , Vocalização Animal , Animais , Vocalização Animal/fisiologia , Aves/fisiologiaRESUMO
Human astrovirus is a positive-sense, single-stranded RNA virus. Astrovirus infection causes gastrointestinal symptoms and can lead to encephalitis in immunocompromised patients. Positive-strand RNA viruses typically utilize host intracellular membranes to form replication organelles, which are potential antiviral targets. Many of these replication organelles are double-membrane vesicles (DMVs). Here, we show that astrovirus infection leads to an increase in DMV formation through a replication-dependent mechanism that requires some early components of the autophagy machinery. Results indicate that the upstream class III phosphatidylinositol 3-kinase (PI3K) complex, but not LC3 conjugation machinery, is utilized in DMV formation. Both chemical and genetic inhibition of the PI3K complex lead to significant reduction in DMVs, as well as viral replication. Elucidating the role of autophagy machinery in DMV formation during astrovirus infection reveals a potential target for therapeutic intervention for immunocompromised patients. IMPORTANCE These studies provide critical new evidence that astrovirus replication requires formation of double-membrane vesicles, which utilize class III phosphatidylinositol 3-kinase (PI3K), but not LC3 conjugation autophagy machinery, for biogenesis. These results are consistent with replication mechanisms for other positive-sense RNA viruses suggesting that targeting PI3K could be a promising therapeutic option for not only astrovirus, but other positive-sense RNA virus infections.
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Mamastrovirus , Fosfatidilinositol 3-Quinase , Replicação Viral , Humanos , Autofagia , Classe III de Fosfatidilinositol 3-Quinases/metabolismo , Membranas Intracelulares/metabolismo , Organelas , Fosfatidilinositol 3-Quinase/metabolismo , Vírus de RNA , Mamastrovirus/fisiologia , Transdução de SinaisRESUMO
OBJECTIVE: The aim of this study was to assess nurse preceptor burnout and examine related factors. BACKGROUND: Nurse preceptors are essential to the provision of optimal hospital-based care. Preceptors guide and support nurses' transition from professional training to practice as well as movement within practice roles. METHODS: As a component of the DevelopYou database, nurse preceptors (N = 210) were surveyed electronically using the BHLex Preceptor Role Questionnaire. Data retrieved from this data set were analyzed. RESULTS: Twenty-eight percent (n = 60) of participants experienced burnout. Most (n = 203, 96.7%) enjoyed their role. Reasons for becoming a preceptor included a love for teaching, a desire to help others, and feelings of responsibility to the profession and the institution. Strategies to enable perceived value of the role focused on activities involving person-to-person interactions. CONCLUSIONS: On the basis of the results of this analysis, it is apparent that nurse preceptors want to feel valued and supported by administration and have opportunities to interact regularly with colleagues.
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Esgotamento Profissional , Preceptoria , Humanos , Emoções , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Although universal mismatch repair (MMR) immunohistochemistry (IHC) in endometrial cancer began at our institution in July 2015, not all eligible patients were referred for genetic testing (GT). In April 2017, genetic counselors obtained IHC data and contacted physicians to approve genetic counseling referrals (GCRs) for Lynch Syndrome (LS) in eligible patients. We assessed if this protocol increased frequency of GCRs and GT in patients with abnormal MMR IHC. METHODS: We retrospectively (7/2015-5/2022) identified patients with abnormal MMR IHC at a large urban hospital. GCRs and GT were compared between cases from 7/2015-4/2017 (pre-protocol) and 5/2017-5/2022 (post-protocol) with chi-square and Fisher's exact tests. RESULTS: Of 794 patients with IHC testing, 177 (22.3%) had abnormal MMR results with 46 (26.0%) meeting criteria for LS screening with GT. Of 46 patients, 16 (34.8%) were identified prior to and 30 (65.2%) after the protocol initiation. GCRs significantly increased from 11/16 (68.8%) to 29/30 (96.7%) in the pre-protocol versus post-protocol groups, p = 0.02. There was no statistically significant difference in GT between groups (10/16, 62.5% vs 26/30, 86.7%, p = 0.07). Of 36 patients who underwent GT, 16 (44.4%) had LS: MSH6, 9; MSH2, 4; PMS2, 2; MLH1, 1. CONCLUSIONS: Increased frequency of GCRs was observed following the change in protocol, which is important as LS screening has clinical implications for patients and their families. Despite this additional effort, approximately 15% who met criteria did not undergo GT; further efforts such as universal germline testing in patients with endometrial cancer should be considered.
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Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias do Endométrio , Feminino , Humanos , Estudos Retrospectivos , Reparo de Erro de Pareamento de DNA , Imuno-Histoquímica , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Endonuclease PMS2 de Reparo de Erro de Pareamento/metabolismo , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Testes Genéticos/métodos , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genéticaRESUMO
OBJECTIVE: This study aimed to evaluate the relationship between peripartum mean arterial pressure (MAP) and postpartum readmission for preeclampsia with severe features. STUDY DESIGN: This is a retrospective case-control study comparing adult parturients readmitted for preeclampsia with severe features to matched nonreadmitted controls. Our primary objective was to evaluate the association between MAP at three time points during the index hospitalization (admission, 24-hour postpartum, and discharge) and readmission risk. We also evaluated readmission risk by age, race, body mass index, and comorbidities. Our secondary aim was to establish MAP thresholds to identify the population at highest risk of readmission. Multivariate logistic regression and chi-squared tests were used to determine the adjusted odds of readmission based on MAP. Receiver operating characteristic analyses were performed to evaluate risk of readmission relative to MAP; optimal MAP thresholds were established to identify those at highest risk of readmission. Pairwise comparisons were made between subgroups after stratifying for history of hypertension, with a focus on readmitted patients with new-onset postpartum preeclampsia. RESULTS: A total of 348 subjects met inclusion criteria, including 174 controls and 174 cases. We found that elevated MAP at both admission (adjusted odds ratio [OR]: 1.37 per 10 mm Hg, p < 0.0001) and 24-hour postpartum (adjusted OR: 1.61 per 10 mm Hg, p = 0.0018) were associated with increased risk of readmission. African American race and hypertensive disorder of pregnancy were independently associated with increased risk of readmission. Subjects with MAP > 99.5 mm Hg at admission or >91.5 mm Hg at 24-hour postpartum had a risk of at least 46% of requiring postpartum readmission for preeclampsia with severe features. CONCLUSION: Admission and 24-hour postpartum MAP correlate with risk of postpartum readmission for preeclampsia with severe features. Evaluating MAP at these time points may be useful for identifying women at higher risk for postpartum readmission. These women may otherwise be missed based on standard clinical approaches and may benefit from heightened surveillance. KEY POINTS: · Existing literature focuses on management of antenatal hypertensive disorders of pregnancy.. · Elevated peripartum MAP is associated with increased odds of readmission for preeclampsia.. · Peripartum MAP may predict readmission risk for de novo postpartum preeclampsia..
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OBJECTIVE: Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality. At present, there are no reliable clinical or laboratory indicators to identify which patients might require blood transfusions during a PPH. Serum lactate has long been used as an early biomarker of tissue hypoperfusion in trauma settings. The aim of this study is to understand serum lactate's role in the management of obstetric hemorrhage. STUDY DESIGN: A retrospective chart review was performed of women who delivered between 2016 and 2019 at our institution and experienced a PPH. The patients were divided into two groups: those with a normal serum lactate level, defined as ≤2 mmol/L, and those with an abnormal serum lactate level, defined as >2 mmol/L. Need for packed red blood cell transfusion, as part of the resuscitation, was assessed for both groups. RESULTS: During the study period, 938 women experienced PPH. Of these, 108 (11.5%) had a normal serum lactate, ≤2 mmol/L, and 830 (88.5%) had an abnormal lactate, >2 mmol/L. Women with elevated lactate levels were more likely to receive a blood transfusion versus those with a normal lactate level (57.0 vs. 46.3%, p = 0.035, respectively). Additionally, the average number of blood transfusions administered was significantly higher in the abnormal lactate group versus in the normal lactate group (1.34 vs. 0.97, respectively, p = 0.004). In a multivariable linear regression model, increasing serum lactate levels were found to be predictive of requiring more than 1 unit of blood (p < 0.001). CONCLUSION: Women with elevated serum lactate levels were more likely to require blood transfusions during a PPH versus those with a normal serum lactate level. Thus, serum lactate levels are useful as an early indicator of requirement for blood transfusion in the management of obstetric hemorrhage. KEY POINTS: · Lactate is a biomarker for blood transfusion in trauma.. · Lactate's role in PPH is unknown.. · Elevated lactate predicts receiving more blood transfusions..
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Hemorragia Pós-Parto , Gravidez , Humanos , Feminino , Hemorragia Pós-Parto/terapia , Estudos Retrospectivos , Transfusão de Sangue , Biomarcadores , LactatosRESUMO
Successful control and prevention of biological invasions depend on identifying traits of non-native species that promote fitness advantages in competition with native species. Here, we show that, among 76 native and non-native woody plants of deciduous forests of North America, invaders express a unique functional syndrome that combines high metabolic rate with robust leaves of longer lifespan and a greater duration of annual carbon gain, behaviours enabled by seasonally plastic xylem structure and rapid production of thin roots. This trait combination was absent in all native species examined and suggests the success of forest invaders is driven by a novel resource-use strategy. Furthermore, two traits alone-annual leaf duration and nuclear DNA content-separated native and invasive species with 93% accuracy, supporting the use of functional traits in invader risk assessments. A trait syndrome reflecting both fast growth capacity and understorey persistence may be a key driver of forest invasions.
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Florestas , Árvores , Carbono/metabolismo , Espécies Introduzidas , Folhas de Planta , Árvores/genéticaRESUMO
BACKGROUND: Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. RESULTS: Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). CONCLUSIONS: The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.
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COVID-19/complicações , COVID-19/mortalidade , Carcinoma/complicações , Carcinoma/mortalidade , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/mortalidade , Hospitalização/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/terapia , Carcinoma/terapia , Feminino , Neoplasias dos Genitais Femininos/terapia , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Gravidade do Paciente , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
OPINION STATEMENT: Poly-ADP-ribose polymerase inhibitors (PARPi) are a class of anti-cancer drugs that target DNA repair pathways and have shown promising efficacy in patients with ovarian cancer in recent clinical trials. To date, there have been 9 FDA PARPi approvals/indications in ovarian cancer since 2014, highlighting the importance of this class of agents in the treatment of ovarian cancer. BRCA1/2-mutated tumors or other forms of homologous recombination deficient (HRD) tumors are particularly susceptible to PARP inhibition and have seen the greatest benefits of improvement in response rate and progression-free survival (PFS) in clinical trials. Patients with homologous recombination-proficient tumors also receive benefit, especially when a nice response to paltinum is noted, but to a lesser extent. PARP inhibitors now have FDA approval and indications in first-line and recurrent maintenance, and treatment. PARP inhibitor use as maintenance therapy in the front-line setting is now considered the standard of care in patients with BRCA1/2 mutations based on the SOLO-1/GOG-3004/ENGOT study. PARP inhibitors are also recommended per ASCO guidelines in all patients with ovarian cancer as front-line maintenance therapy based on the PRIMA/ENGOT-OV26/GOG-3012 trial. The combination of PARP inhibitor, olaparib, and the anti-angiogenesis inhibitor bevacizumab is also approved as maintenance therapy after front-line chemotherapy treatment in patients with HRD tumors and is an option for patients who have initiated bevacizumab with their chemotherapy treatment. PARPi are also FDA approved and can be utilized as a treatment in third-line and beyond in recurrent ovarian cancer patients with BRCA1/2 mutations and HRD tumors. In this review, we will cover in detail when PARP inhibitor use is appropriate in ovarian cancer, as well as the various clinical factors to take into consideration when selecting a PARP inhibitor regimen.
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Antineoplásicos , Neoplasias Ovarianas , Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêuticoRESUMO
BACKGROUND: Mounting evidence suggests disproportionate coronavirus disease 2019 (COVID-19) hospitalizations and deaths because of racial disparities. The association of race in a cohort of gynecologic oncology patients with severe acute respiratory syndrome-coronavirus 2 infection is unknown. METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 New York City area hospital systems. A multivariable mixed-effects logistic regression model accounting for county clustering was used to analyze COVID-19-related hospitalization and mortality. RESULTS: Of 193 patients who had gynecologic cancer and COVID-19, 67 (34.7%) were Black, and 126 (65.3%) were non-Black. Black patients were more likely to require hospitalization compared with non-Black patients (71.6% [48 of 67] vs 46.0% [58 of 126]; P = .001). Of 34 (17.6%) patients who died from COVID-19, 14 (41.2%) were Black. Among those who were hospitalized, compared with non-Black patients, Black patients were more likely to: have ≥3 comorbidities (81.1% [30 of 37] vs 59.2% [29 of 49]; P = .05), to reside in Brooklyn (81.0% [17 of 21] vs 44.4% [12 of 27]; P = .02), to live with family (69.4% [25 of 36] vs 41.6% [37 of 89]; P = .009), and to have public insurance (79.6% [39 of 49] vs 53.4% [39 of 73]; P = .006). In multivariable analysis, among patients aged <65 years, Black patients were more likely to require hospitalization compared with non-Black patients (odds ratio, 4.87; 95% CI, 1.82-12.99; P = .002). CONCLUSIONS: Although Black patients represented only one-third of patients with gynecologic cancer, they accounted for disproportionate rates of hospitalization (>45%) and death (>40%) because of COVID-19 infection; younger Black patients had a nearly 5-fold greater risk of hospitalization. Efforts to understand and improve these disparities in COVID-19 outcomes among Black patients are critical.
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Negro ou Afro-Americano/estatística & dados numéricos , COVID-19/etnologia , Neoplasias dos Genitais Femininos/etnologia , Disparidades nos Níveis de Saúde , População Branca/estatística & dados numéricos , Adulto , Idoso , COVID-19/complicações , COVID-19/virologia , Feminino , Neoplasias dos Genitais Femininos/complicações , Hospitalização/estatística & dados numéricos , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Cidade de Nova Iorque , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/fisiologia , Análise de SobrevidaRESUMO
Metabolic syndrome increases the risk of severe disease due to viral infection. Yet few studies have assessed the pathogenesis of respiratory viruses in high-risk populations. Here, we summarize how metabolic dysregulation impairs immune responses, and we define the role of metabolism during influenza virus and coronavirus infections. We also discuss the use of various in vitro, in vivo, and ex vivo models to elucidate the contributions of host factors to viral susceptibility, immunity, and disease severity.
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Infecções por Coronavirus/complicações , Suscetibilidade a Doenças , Influenza Humana/complicações , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Animais , Biomarcadores , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Humanos , Influenza Humana/virologia , Síndrome Metabólica/diagnósticoRESUMO
BACKGROUND: The Will Rogers phenomenon [WRP] describes an apparent improvement in outcome for patients' group due to tumor grade reclassification. Staging of cancers is important to select appropriate treatment and to estimate prognosis. The WRP has been described as one of the most important biases limiting the use of historical cohorts when comparing survival or treatment. The main purpose of this study is to assess whether the WRP exists with the move from the AJCC 7th to AJCC 8th edition in breast cancer [BC] staging, and if racial differences are manifested in the expression of the WRP. METHODS: This is a retrospective analysis of 300 BC women (2007-2017) at an academic medical center. Overall survival [OS] and disease-free survival [DFS] was estimated by Kaplan-Meier analysis. Bi and multi-variate Cox regression analyses was used to identify racial factors associated with outcomes. RESULTS: Our patient cohort included 30.3% Caucasians [Whites] and 69.7% African-Americans [Blacks]. Stages I, II, III, and IV were 46.2, 26.3, 23.1, and 4.4% of Whites; 28.7, 43.1, 24.4, and 3.8% of Blacks respectively, in anatomic staging (p = 0.043). In prognostic staging, 52.8, 18.7, 23, and 5.5% were Whites while 35, 17.2, 43.5, and 4.3% were Blacks, respectively (p = 0.011). A total of Whites (45.05% vs. 47.85%) Blacks, upstaged. Whites (16.49% vs. 14.35%) Blacks, downstaged. The remaining, 38.46 and 37.79% patients had their stages unchanged. With a median follow-up of 54 months, the Black patients showed better stage-by-stage 5-year OS rates using 8th edition compared to the 7th edition (p = 0.000). Among the Whites, those who were stage IIIA in the 7th but became stage IB in the 8th had a better prognosis than stages IIA and IIB in the 8th (p = 0.000). The 8th showed complex results (p = 0.176) compared to DFS estimated using the 7th edition (p = 0.004). CONCLUSION: The WRP exists with significant variability in the move from the AJCC 7th to the 8th edition in BC staging (both White and Black patients). We suggest that caution needs to be exercised when results are compared across staging systems to account for the WRP in the interpretation of the data.
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Neoplasias da Mama , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Centros Médicos Acadêmicos/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Mama/patologia , Neoplasias da Mama/etnologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Intervalo Livre de Doença , Seguimentos , Disparidades nos Níveis de Saúde , Estimativa de Kaplan-Meier , Mississippi/epidemiologia , Gradação de Tumores/estatística & dados numéricos , Estadiamento de Neoplasias/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos , Provedores de Redes de Segurança/estatística & dados numéricos , Taxa de Sobrevida , BrancosRESUMO
BACKGROUND: In women with BRCA mutations, risk-reducing bilateral salpingo-oophorectomy has been shown to decrease gynecologic cancer-specific and overall mortality. The National Comprehensive Cancer Network recommends that patients with BRCA mutations undergo risk-reducing bilateral salpingo-oophorectomy between the ages of 35 and 40 years for BRCA1 mutation carriers and between the ages of 40 and 45 years for BRCA2 mutation carriers or after childbearing is complete. Currently, uptake and timing of risk-reducing bilateral salpingo-oophorectomy and reasons for delays in risk-reducing bilateral salpingo-oophorectomy are not well understood. OBJECTIVE: We sought to evaluate uptake and timing of risk-reducing bilateral salpingo-oophorectomy among women with BRCA1 and BRCA2 mutations concerning the National Comprehensive Cancer Network guidelines and reasons for delays in risk-reducing bilateral salpingo-oophorectomy. STUDY DESIGN: In this retrospective chart review, we identified women with BRCA1 and BRCA2 mutations who discussed risk-reducing bilateral salpingo-oophorectomy with a provider between 2012 and 2021. Uptake of risk-reducing bilateral salpingo-oophorectomy was documented, and patients were classified as having timely or delay in risk-reducing bilateral salpingo-oophorectomy based on the National Comprehensive Cancer Network guidelines. For those with delay in risk-reducing bilateral salpingo-oophorectomy, reasons cited for delay were collected. Comparative statistical analyses were performed to evaluate characteristics of those with timely vs delayed risk-reducing bilateral salpingo-oophorectomy. A multivariable logistic regression model was used to evaluate the associations among factors related to timing of risk-reducing bilateral salpingo-oophorectomy. RESULTS: We identified 638 BRCA1 and BRCA2 mutation carriers seen between 2012 and 2021. Of these patients, 306 (48.0%) had undergone risk-reducing bilateral salpingo-oophorectomy and 332 (52.0%) had not. When evaluating the timing of risk-reducing bilateral salpingo-oophorectomy, 136 (21.3%) underwent timely risk-reducing bilateral salpingo-oophorectomy, 239 (37.5%) had delays in risk-reducing bilateral salpingo-oophorectomy, and 263 (41.2%) had not undergone risk-reducing bilateral salpingo-oophorectomy but were younger than the National Comprehensive Cancer Network age guidelines; therefore, they were neither timely nor delayed. Patients with delay in risk-reducing bilateral salpingo-oophorectomy were significantly older at the time of genetic testing than those with timely risk-reducing bilateral salpingo-oophorectomy (mean, 49.8 vs 36.3 years; P<.001). Of the 306 patients who underwent risk-reducing bilateral salpingo-oophorectomy, those with delayed risk-reducing bilateral salpingo-oophorectomy had a significantly shorter interval between BRCA identification and risk-reducing bilateral salpingo-oophorectomy than those with timely risk-reducing bilateral salpingo-oophorectomy (median, 8.7 vs 17.6 months; P<.001). Patients with delay in risk-reducing bilateral salpingo-oophorectomy were more likely to have a personal history of cancer than those with timely risk-reducing bilateral salpingo-oophorectomy (49.8% vs 37.5%; P=.028). Of the 239 women with delay in risk-reducing bilateral salpingo-oophorectomy, 188 (78.7%) had delayed BRCA mutation identification, 29 (12.1%) had menopausal concerns, 17 (7.1%) had ongoing cancer treatment, 12 (5.0%) had coordination with breast surgery, 20 (8.4%) had miscellaneous reasons, and 19 (7.9%) had no reason documented. In the multivariate model, older age at BRCA diagnosis (odds ratio, 0.73; 95% confidence interval, 0.68-0.78; P<.001) was significantly associated with delayed risk-reducing bilateral salpingo-oophorectomy timing; those with BRCA2 mutation type were 7.54 times as likely to have timely risk-reducing bilateral salpingo-oophorectomy than BRCA1 mutation carriers (odds ratio, 7.54; 95% confidence, 3.70-16.42; P<.001). CONCLUSION: Nearly 38% of BRCA1 and BRCA2 mutation carriers undergo or have yet to undergo risk-reducing bilateral salpingo-oophorectomy over the recommended National Comprehensive Cancer Network age. The most common reason for the delay in risk-reducing bilateral salpingo-oophorectomy was delayed identification of BRCA mutation, noted in 79% of patients with delayed risk-reducing bilateral salpingo-oophorectomy. Timely genetic testing for eligible patients can increase appropriately timed risk-reducing bilateral salpingo-oophorectomy for the prevention of ovarian cancer and reduction of mortality in BRCA mutation carriers.
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Genes BRCA1 , Genes BRCA2 , Mutação , Procedimentos Cirúrgicos Profiláticos/estatística & dados numéricos , Salpingo-Ooforectomia/estatística & dados numéricos , Adulto , Fatores Etários , Feminino , Heterozigoto , Humanos , Neoplasias Ovarianas/prevenção & controle , Estudos Retrospectivos , Tempo para o TratamentoRESUMO
STUDY OBJECTIVE: Obesity is a growing worldwide epidemic, and patients classified as obese undergoing gynecologic robotic surgery are at increased risk for surgical complications. This study aimed to evaluate the feasibility and outcomes of a surgical safety protocol known as the High BMI [Body Mass Index] Pathway (HBP) for patients with BMI ≥40 kg/m2 undergoing planned robotic hysterectomy. Our primary outcome was the rate of all-cause perioperative complications in patients undergoing surgery with the use of the HBP. DESIGN: A retrospective cohort study. SETTING: An academic teaching hospital. PATIENTS: A total of 138 patients classified as morbidly obese (BMI ≥40 kg/m2) undergoing robotic hysterectomy. INTERVENTIONS: The HBP was developed by a multidisciplinary team and was instituted on January 1, 2016, as a quality improvement project. Patients classified as morbidly obese undergoing robotic hysterectomy after this date were compared with consecutive historical controls. MEASUREMENTS AND MAIN RESULTS: Seventy-two patients underwent robotic hysterectomies on the HBP and were compared with 66 controls. There were no differences in age, BMI, blood loss, number of comorbidities, or cancer diagnosis. Since the implementation of the HBP, there has been a decrease in anesthesia time (-57.0 minutes; p = .001) and total operating room time (-47.0 min; p = .020), as well as lower estimated blood loss (median 150 mL [interquartile range 100-200] vs 200 mL [interquartile range 100-300]; p = .002) and reduction in overnight hospital admissions (33.3% vs 63.6%; p <.001). In the HBP group, there were fewer all-cause complications (19.4% vs 37.9%; p = .023) and infectious complications (8.3% vs 33.3%; p = .001), and there was no increase in the readmission rates (p = .400). In multivariable analysis, the HBP reduced all-cause complications (odds ratio 0.353; p = .010) after controlling for the covariate (total time in the operating room). CONCLUSION: The HBP is a feasible method of optimizing the outcome for patients classified as morbidly obese undergoing major gynecologic surgery. Initiation of the HBP can lead to decreased anesthesia and operating times, all-cause complications, and overnight hospital admissions without increasing readmission rates.
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Obesidade Mórbida , Procedimentos Cirúrgicos Robóticos , Robótica , Feminino , Humanos , Histerectomia/efeitos adversos , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversosRESUMO
BACKGROUND: New York City (NYC) is the epicenter of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) in the United States. Clinical characteristics and outcomes of vulnerable populations, such as those with gynecologic cancer who develop COVID-19 infections, is limited. METHODS: Patients from 6 NYC-area hospital systems with known gynecologic cancer and a COVID-19 diagnosis were identified. Demographic and clinical outcome data were abstracted through a review of electronic medical records. RESULTS: Records for 121 patients with gynecologic cancer and COVID-19 were abstracted; the median age at the COVID-19 diagnosis was 64.0 years (interquartile range, 51.0-73.0 years). Sixty-six of the 121 patients (54.5%) required hospitalization; among the hospitalized patients, 45 (68.2%) required respiratory intervention, 20 (30.3%) were admitted to the intensive care unit, and 9 (13.6%) underwent invasive mechanical ventilation. Seventeen patients (14.0%) died of COVID-19 complications. No patient requiring mechanical ventilation survived. On multivariable analysis, hospitalization was associated with an age ≥64 years (risk ratio [RR], 1.73; 95% confidence interval [CI], 1.18-2.51), African American race (RR, 1.56; 95% CI, 1.13-2.15), and 3 or more comorbidities (RR, 1.43; 95% CI, 1.03-1.98). Only recent immunotherapy use (RR, 3.49; 95% CI, 1.08-11.27) was associated with death due to COVID-19 on multivariable analysis; chemotherapy treatment and recent major surgery were not predictive of COVID-19 severity or mortality. CONCLUSIONS: The case fatality rate among gynecologic oncology patients with a COVID-19 infection is 14.0%. Recent immunotherapy use is associated with an increased risk of mortality related to COVID-19 infection. LAY SUMMARY: The case fatality rate among gynecologic oncology patients with a coronavirus disease 2019 (COVID-19) infection is 14.0%; there is no association between cytotoxic chemotherapy and cancer-directed surgery and COVID-19 severity or death. As such, patients can be counseled regarding the safety of continued anticancer treatments during the pandemic. This is important because the ability to continue cancer therapies for cancer control and cure is critical.
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COVID-19/mortalidade , COVID-19/terapia , Neoplasias dos Genitais Femininos/epidemiologia , Idoso , COVID-19/epidemiologia , COVID-19/etiologia , Comorbidade , Feminino , Neoplasias dos Genitais Femininos/terapia , Hospitalização , Humanos , Imunoterapia , Unidades de Terapia Intensiva , Pessoa de Meia-Idade , Cidade de Nova Iorque , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: Elevated inflammatory markers are predictive of COVID-19 infection severity and mortality. It is unclear if these markers are associated with severe infection in patients with cancer due to underlying tumor related inflammation. We sought to further understand the inflammatory response related to COVID-19 infection in patients with gynecologic cancer. METHODS: Patients with a history of gynecologic cancer hospitalized for COVID-19 infection with available laboratory data were identified. Admission laboratory values and clinical outcomes were abstracted from electronic medical records. Severe infection was defined as infection requiring ICU admission, mechanical ventilation, or resulting in death. RESULTS: 86 patients with gynecologic cancer were hospitalized with COVID-19 infection with a median age of 68.5 years (interquartile range (IQR), 59.0-74.8). Of the 86 patients, 29 (33.7%) patients required ICU admission and 25 (29.1%) patients died of COVID-19 complications. Fifty (58.1%) patients had active cancer and 36 (41.9%) were in remission. Patients with severe infection had significantly higher ferritin (median 1163.0 vs 624.0 ng/mL, p < 0.01), procalcitonin (median 0.8 vs 0.2 ng/mL, p < 0.01), and C-reactive protein (median 142.0 vs 62.3 mg/L, p = 0.02) levels compared to those with moderate infection. White blood cell count, lactate, and creatinine were also associated with severe infection. D-dimer levels were not significantly associated with severe infection (p = 0.20). CONCLUSIONS: The inflammatory markers ferritin, procalcitonin, and CRP were associated with COVID-19 severity in gynecologic cancer patients and may be used as prognostic markers at the time of admission.
Assuntos
Proteína C-Reativa/análise , COVID-19/diagnóstico , Neoplasias dos Genitais Femininos/imunologia , Inflamação/diagnóstico , Idoso , Biomarcadores/sangue , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Feminino , Neoplasias dos Genitais Femininos/sangue , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/diagnóstico , Humanos , Inflamação/sangue , Inflamação/imunologia , Contagem de Leucócitos , Pessoa de Meia-Idade , Admissão do Paciente , Prognóstico , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de DoençaRESUMO
Intermittent breeding, in which an adult skips a breeding opportunity, can represent a non-adaptive constraint or an adaptive response to the tradeoff between current and future reproduction. In group-living animals, the social group may also affect the frequency of reproduction, but this possibility has received little attention. Here we use an 11-year data set to investigate intermittent breeding in the greater ani (Crotophaga major), a tropical bird that nests in stable breeding groups containing several unrelated co-breeding females. Population-wide, an average of 62% of females laid eggs in a given year (range 35-84%), and the average female failed to lay eggs once every 3.2 years. We found little support for the hypothesis that intermittent breeding reflects a tradeoff between current and future reproduction: breeding in year t did not affect a female's likelihood of breeding in year t + 1, and clutch size in year t did not affect clutch size in year t + 1. Increases in clutch size were associated with decreases in egg mass for eggs laid at the end of that clutch, but this did not affect subsequent nesting attempts. However, reproductive skipping was associated with changes in group membership. Females whose groups changed in composition after year t were significantly less likely to breed in year t + 1 than females whose groups remained stable. These results indicate that breeding group stability influences the frequency of reproduction, suggesting that transitions between groups may be costly to females and their mates.
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Aves , Comportamento de Nidação , Animais , Cruzamento , Tamanho da Ninhada , Feminino , ReproduçãoRESUMO
Hydrophobin-fused domain III of dengue envelope proteins serotypes 1 and 2 were expressed in Rachiplusia nu larvae and purified by aqueous two-phase system. This biotechnological approach of hydrophobin-fused proteins, which allowed obtaining 97.7 µg/larva of fusion protein DomIII serotype 1 and 61.4 µg/larva of fusion protein DomIII serotype 2, represents an integrated strategy for simple production of recombinant antigens. Purified fusion proteins induced serotype-specific neutralizing antibodies without cross-reaction against other serotypes and arboviruses after mouse immunization. hydrophobin-fused domain III of dengue envelope protein could be a promising strategy for easy and low-cost production of components of a tetravalent sub-unit vaccine against dengue.
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Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Vacinas contra Dengue/genética , Vírus da Dengue/genética , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Domínios Proteicos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Sorogrupo , Células Sf9 , Spodoptera , Proteínas do Envelope Viral/genéticaRESUMO
Application of restriction endonuclease (REase) enzymes for specific detection of nucleic acids provides for high assay specificity, convenience and low cost. A direct restriction assay format is based on the specific enzymatic cleavage of a target-probe hybrid that is accompanied with the release of a molecular marker into the solution, enabling target quantification. This format has the detection limit in nanomolar range. The assay sensitivity is improved drastically to the attomolar level by implementation of exponential signal amplification that is based on a cascade of self-perpetuating restriction endonuclease reactions. The cascade is started by action of an amplification "trigger". The trigger is immobilized through a target-specific probe. Upon the target probe hybridization followed with specific cleavage, the trigger is released into the reaction solution. The solution is then added to the assay amplification stage, and the free trigger induces cleavage of amplification probes, thus starting the self-perpetuating cascade of REase-catalyzed events. Continuous cleavage of new amplification probes leads to the exponential release of new triggers and rapid exponential signal amplification. The proposed formats exemplify a valid isothermal alternative to qPCR with similar sensitivity achieved at a fraction of the associated costs, time and labor. Advantages and challenges of the approach are discussed.
Assuntos
Enzimas de Restrição do DNA , DNA/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico , Limite de Detecção , Hibridização de Ácido Nucleico , Sondas de Ácido NucleicoRESUMO
MAIN CONCLUSIONS: This study demonstrated that freeze-induced hydraulic failure varies between two Vitis species that have different xylem vessel frequency and grouping. However, seasonal recovery of young grapevines was similar between the species. Sub-freezing temperatures after budburst represent a major threat for the cultivation of fruit crops in temperate regions. Freeze stress might disrupt xylem hydraulic functionality and plant growth; however, it is unclear if hydraulic traits influence the ability of woody plants to cope with freeze stress. We investigated if a grapevine species (Vitis hybrid) with earlier budburst had anatomical traits that cause higher freeze-induced hydraulic failure but also confer a greater ability for seasonal recovery compared to a Vitis vinifera species. Two-year-old Vitis hybrid and vinifera grapevines were container-grown outdoors, assigned to either a control (n = 40) or a freeze-stressed (n = 40) treatment and exposed to a controlled-temperature (- 4 °C) freeze stress shortly after budburst. We found that the Vitis hybrid had greater stem-specific hydraulic conductivity (Ks) and was more vulnerable to freeze-induced embolism compared to the V. vinifera species, which exhibited a less efficient but safer water transport strategy. Seventy-two hours after the freeze stress, Ks of freeze-stressed V. vinifera was 77.8% higher than that of the control, indicating hydraulic recovery. While the two species did not differ in xylem vessel diameter, Vitis hybrid exhibited higher vessel frequency and percentage of vessel grouping, which could explain its higher Ks and greater freeze-induced Ks loss compared to the V. vinifera vines. While the two species varied in the short-term hydraulic response, they exhibited similar and full hydraulic and vegetative recovery by midseason, including bud freeze tolerance during the following fall and mid-winter.