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1.
Contraception ; : 110488, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38763274

RESUMO

OBJECTIVE: To systematically review the effect of contraceptive methods following gestational trophoblastic disease (GTD) on timing of beta-hCG remission, risk of post-molar gestational trophoblastic neoplasia (GTN), risk of unintended incident pregnancy, and interactions between contraceptive methods and disease treatment. STUDY DESIGN: We conducted a search of primary literature with search terms related to GTD and contraception through April 2023 in PubMed and extrapolated our search to other platforms. Randomized controlled trials, observational studies and case reports were eligible for inclusion if they reported on patients with known GTD who received a contraceptive method for pregnancy prevention. Data was abstracted on our main outcomes of interest: timing of beta-hCG remission, risk of post-molar GTN, risk of unintended incident pregnancy, and interactions between contraceptive methods and cancer-directed systemic disease treatment (e.g. chemotherapy). At least two authors reviewed manuscripts at each screening stage with consensus reached before data extraction. Quality assessment checklists were used to assess risk of bias for the different study types. RESULTS: 5,105 studies were identified in the database search, of which 42 were included for analysis. 8,294 participants were evaluated. Over half of the studies were case reports and only two were randomized controlled trials. While there was sparse data on all outcomes, no differences were noted in beta-hCG monitoring, risk of post-molar GTN or incident pregnancies between different contraceptive types. Interactions between contraceptive methods and cancer-directed systemic disease treatment (e.g. chemotherapy) or specific adverse events of contraceptive methods were not identified. CONCLUSIONS: Data on contraceptive use following GTD is limited, but use of both hormonal and non-hormonal modern contraceptive methods appears safe. Counseling patients on the full range of contraceptive methods is important to help patients achieve their reproductive health goals and minimize the risk of disease progression through incomplete beta-hCG monitoring prior to future pregnancy. IMPLICATIONS: Hormonal and non-hormonal contraceptive options may be used by patients following gestational trophoblastic disease without apparent changes in beta-hCG regression or risk of post-molar gestational trophoblastic neoplasia.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38588577

RESUMO

Female survivors of young adult (YA) cancers are at risk of fertility impacts following cancer treatment. For these women, fertility-related distress is both prevalent and persistent. Yet there is little research regarding survivors' perspectives on alternative family-building options, particularly adoption. This exploratory secondary data analysis analyzed semistructured interviews and explored survivors' views of adoption. Overall, female YA survivors reported openness to adoption as a possible substitute for biological conception and an alternative to fertility preservation. It is imperative that this population receives support in decision-making around and consideration of the unique barriers to adoption for cancer survivors.

3.
J Immunother Cancer ; 12(4)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38642938

RESUMO

BACKGROUND: Colitis caused by checkpoint inhibitors (CPI) is frequent and is treated with empiric steroids, but CPI colitis mechanisms in steroid-experienced or refractory disease are unclear. METHODS: Using colon biopsies and blood from predominantly steroid-experienced CPI colitis patients, we performed multiplexed single-cell transcriptomics and proteomics to nominate contributing populations. RESULTS: CPI colitis biopsies showed enrichment of CD4+resident memory (RM) T cells in addition to CD8+ RM and cytotoxic CD8+ T cells. Matching T cell receptor (TCR) clonotypes suggested that both RMs are progenitors that yield cytotoxic effectors. Activated, CD38+ HLA-DR+ CD4+ RM and cytotoxic CD8+ T cells were enriched in steroid-experienced and a validation data set of steroid-naïve CPI colitis, underscoring their pathogenic potential across steroid exposure. Distinct from ulcerative colitis, CPI colitis exhibited perturbed stromal metabolism (NAD+, tryptophan) impacting epithelial survival and inflammation. Endothelial cells in CPI colitis after anti-TNF and anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) upregulated the integrin α4ß7 ligand molecular vascular addressin cell adhesion molecule 1 (MAdCAM-1), which may preferentially respond to vedolizumab (anti-α4ß7). CONCLUSIONS: These findings nominate CD4+ RM and MAdCAM-1+ endothelial cells for targeting in specific subsets of CPI colitis patients.


Assuntos
Linfócitos T CD8-Positivos , Colite , Humanos , Células Endoteliais , Inibidores do Fator de Necrose Tumoral , Colite/induzido quimicamente , Colite/tratamento farmacológico , Linfócitos T CD4-Positivos , Esteroides/farmacologia , Esteroides/uso terapêutico , Células Estromais
4.
Curr Treat Options Oncol ; 25(1): 1-19, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38172449

RESUMO

OPINION STATEMENT: Antibody-drug conjugates (ADCs) are a novel class of targeted cancer therapies with the ability to selectively deliver a cytotoxic drug to a tumor cell using a monoclonal antibody linked to a cytotoxic payload. The technology of ADCs allows for tumor-specificity, improved efficacy, and decreased toxicity compared to standard chemotherapy. Common toxicities associated with ADC use include ocular, pulmonary, hematologic, and neurologic toxicities. Several ADCs have been approved by the United States Food and Drug Administration (FDA) for the management of patients with recurrent or metastatic gynecologic cancers, a population with poor outcomes and limited effective treatment options. The first FDA-approved ADC for recurrent or metastatic cervical cancer was tisotumab vedotin, a tissue factor-targeting agent, after demonstrating response in the innovaTV 204 trial. Mirvetuximab soravtansine targets folate receptor alpha and is approved for use in patients with folate receptor alpha-positive, platinum-resistant, epithelial ovarian cancer based on results from the SORAYA trial. While there are no FDA-approved ADCs for the treatment of uterine cancer, trastuzumab deruxtecan, an anti-human epidermal growth factor receptor 2 (HER2) agent, is actively being investigated. In this review, we will describe the structure and mechanism of action of ADCs, discuss their toxicity profiles, review ADCs both approved and under investigation for the management of gynecologic cancers, and discuss mechanisms of ADC resistance.


Assuntos
Antineoplásicos , Neoplasias dos Genitais Femininos , Imunoconjugados , Neoplasias Ovarianas , Humanos , Feminino , Receptor 1 de Folato/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Imunoconjugados/efeitos adversos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico
5.
Appl Clin Inform ; 15(2): 204-211, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38232748

RESUMO

OBJECTIVES: To compare the ability of different electronic health record alert types to elicit responses from users caring for cancer patients benefiting from goals of care (GOC) conversations. METHODS: A validated question asking if the user would be surprised by the patient's 6-month mortality was built as an Epic BestPractice Advisory (BPA) alert in three versions-(1) Required on Open chart (pop-up BPA), (2) Required on Close chart (navigator BPA), and (3) Optional Persistent (Storyboard BPA)-randomized using patient medical record number. Meaningful responses were defined as "Yes" or "No," rather than deferral. Data were extracted over 6 months. RESULTS: Alerts appeared for 685 patients during 1,786 outpatient encounters. Measuring encounters where a meaningful response was elicited, rates were highest for Required on Open (94.8% of encounters), compared with Required on Close (90.1%) and Optional Persistent (19.7%) (p < 0.001). Measuring individual alerts to which responses were given, they were most likely meaningful with Optional Persistent (98.3% of responses) and least likely with Required on Open (68.0%) (p < 0.001). Responses of "No," suggesting poor prognosis and prompting GOC, were more likely with Optional Persistent (13.6%) and Required on Open (10.3%) than with Required on Close (7.0%) (p = 0.028). CONCLUSION: Required alerts had response rates almost five times higher than optional alerts. Timing of alerts affects rates of meaningful responses and possibly the response itself. The alert with the most meaningful responses was also associated with the most interruptions and deferral responses. Considering tradeoffs in these metrics is important in designing clinical decision support to maximize success.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Neoplasias dos Genitais Femininos , Sistemas de Registro de Ordens Médicas , Humanos , Feminino , Registros Eletrônicos de Saúde , Prognóstico , Comunicação
6.
Artigo em Inglês | MEDLINE | ID: mdl-38294823

RESUMO

Purpose: To examine the impact of financial costs on fertility preservation decisions among female young adults (YAs) with cancer. Methods: Female YAs (N = 18; aged 21-36) with a history of cancer and oncology providers (N = 12) were recruited from an National Cancer Institute-designated comprehensive cancer center in a state without insurance coverage for fertility preservation. YAs and providers completed individual interviews and a brief online assessment. Qualitative description using thematic analysis was used to identify, analyze, and report common themes. Descriptive statistics was used to characterize the sample. Results: Female YAs and oncology providers highlighted the critical role that high out-of-pocket costs play in YAs' fertility preservation decisions along with the value that enhanced insurance coverage for fertility preservation would have for increasing female YAs' access to and utilization of fertility preservation. Although providers were concerned about preservation costs for their patients, they reported that their concerns did not impact whether they referred interested female YAs to reproductive specialists. Oncology providers expressed concern about inequities in utilization of fertility preservation for female and racially/ethnically minoritized YAs that were exacerbated by the high out-of-pocket fertility preservation costs. Conclusion: Cost is a significant barrier to fertility preservation for female YA cancer patients. Female YAs of reproductive age may benefit from decision support tools to assist with balancing the cost of fertility preservation with their values and family building goals. Policy-relevant interventions may mitigate cost barriers and improve access to care.

7.
Gynecol Oncol ; 179: 70-78, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37944328

RESUMO

OBJECTIVE: To compare radical hysterectomy case volume, cancer stage, and biopsy-to-treatment time of invasive cervical cancer diagnosed before and after onset of the COVID-19 pandemic. METHODS: In a multi-institution retrospective cohort study conducted at 6 large, geographically diverse National Cancer Institute-designated cancer centers, patients treated for newly diagnosed invasive cervical cancer were classified into 2 temporal cohorts based on date of first gynecologic oncology encounter: (1) Pre-Pandemic: 3/1/2018-2/28/2020; (2) Pandemic & Recovery: 4/1/2020-12/31/2021. The primary outcome was total monthly radical hysterectomy case volume. Secondary outcomes were stage at diagnosis and diagnosis-to-treatment time. Statistical analyses used chi-squared and two sample t-tests. RESULTS: Between 3/1/2018-12/31/2021, 561 patients were diagnosed with cervical cancer. The Pre-Pandemic and Pandemic & Recovery cohorts had similar age, race, ethnicity, smoking status, and Body Mass Index (BMI). During Pandemic & Recovery, the mean monthly radical hysterectomy case volume decreased from 7[SD 2.8] to 5[SD 2.0] (p = 0.001), the proportion of patients diagnosed with Stage I disease dropped from 278/561 (49.5%) to 155/381 (40.7%), and diagnosis of stage II-IV disease increased from 281/561 (50.1%) to 224/381 (58.8%). Primary surgical management was less frequent (38.3% Pandemic & Recovery versus 46.7% Pre-Pandemic, p = 0.013) and fewer surgically-treated patients received surgery within 6 weeks of diagnosis (27.4% versus 38.9%; p = 0.025). CONCLUSIONS: Lower radical hysterectomy case volume, a shift to higher cervical cancer stage, and delay in surgical therapy were observed across the United States following the COVID-19 outbreak. Decreased surgical volume may result from lower detection of early-stage disease or other factors.


Assuntos
COVID-19 , Neoplasias do Colo do Útero , Estados Unidos/epidemiologia , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , COVID-19/epidemiologia , Estudos Retrospectivos , Pandemias , National Cancer Institute (U.S.) , Histerectomia/efeitos adversos , Estadiamento de Neoplasias
9.
bioRxiv ; 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37808790

RESUMO

Antitumor immunity is driven by CD8 T cells, yet we lack signatures for the exceptional effectors in tumors, amongst the vast majority of CD8 T cells undergoing exhaustion. By leveraging the measurement of a canonical T cell activation protein (CD69) together with its RNA (Cd69), we found a larger classifier for TCR stimulation-driven effector states in vitro and in vivo. This revealed exceptional 'star' effectors-highly functional cells distinguished amidst progenitor and terminally exhausted cells. Although rare in growing mouse and human tumors, they are prominent in mice during T cell-mediated tumor clearance, where they engage with tumor antigen and are superior in tumor cell killing. Employing multimodal CITE-Seq allowed de novo identification of similar rare effectors amidst T cell populations in human cancer. The identification of rare and exceptional immune states provides rational avenues for enhancement of antitumor immunity.

10.
JMIR Hum Factors ; 10: e49438, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37751239

RESUMO

BACKGROUND: Dashboards and interactive displays are becoming increasingly prevalent in most health care settings and have the potential to streamline access to information, consolidate disparate data sources and deliver new insights. Our research focuses on intensive care units (ICUs) which are heavily instrumented, critical care environments that generate vast amounts of data and frequently require individualized support for each patient. Consequently, clinicians experience a high cognitive load, which can translate to suboptimal performance. The global COVID-19 pandemic exacerbated this problem by generating a large number of additional hospitalizations, which necessitated a new tool that would help manage ICUs' census. In a previous study, we interviewed clinicians at the University Hospitals Bristol and Weston National Health Service Foundation Trust to capture the requirements for bespoke dashboards that would alleviate this problem. OBJECTIVE: This study aims to design, implement, and evaluate an ICU dashboard to allow for monitoring of the high volume of patients in need of critical care, particularly tailored to high-demand situations, such as those seen during the COVID-19 pandemic. METHODS: Building upon the previously gathered requirements, we developed a dashboard, integrated it within the ICU of a National Health Service trust, and allowed all staff to access our tool. For evaluation purposes, participants were recruited and interviewed following a 25-day period during which they were able to use the dashboard clinically. The semistructured interviews followed a topic guide aimed at capturing the usability of the dashboard, supplemented with additional questions asked post hoc to probe themes established during the interview. Interview transcripts were analyzed using a thematic analysis framework that combined inductive and deductive approaches and integrated the Technology Acceptance Model. RESULTS: A total of 10 participants with 4 different roles in the ICU (6 consultants, 2 junior doctors, 1 nurse, and 1 advanced clinical practitioner) participated in the interviews. Our analysis generated 4 key topics that prevailed across the data: our dashboard met the usability requirements of the participants and was found useful and intuitive; participants perceived that it impacted their delivery of patient care by improving the access to the information and better equipping them to do their job; the tool was used in a variety of ways and for different reasons and tasks; and there were barriers to integration of our dashboard into practice, including familiarity with existing systems, which stifled the adoption of our tool. CONCLUSIONS: Our findings show that the perceived utility of the dashboard had a positive impact on the clinicians' workflows in the ICU. Improving access to information translated into more efficient patient care and transformed some of the existing processes. The introduction of our tool was met with positive reception, but its integration during the COVID-19 pandemic limited its adoption into practice.

11.
Gynecol Oncol Rep ; 49: 101260, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37655046

RESUMO

Objectives: The Gynecologic Oncology Postoperative Opioid use Predictive (GO-POP) calculator is a validated tool to provide evidence-based guidance on post-operative opioid prescribing. The objective of this study was to evaluate the impact of the implementation of GO-POP within an academic Gynecologic Oncology division. Methods: Two cohorts of patients (pre-implementation and post-implementation) who underwent surgery were compared with reference to GO-POP calculator implementation. All patients were included in the post-implementation group, regardless of GO-POP calculator use. An additional expanded-implementation cohort was used to compare pain control between GO-POP users and non-GO-POP users prospectively. Wilcoxon rank sum tests or ANOVA for continuous variables and Chi-square or Fisher's exact tests were used to categorical variables. Results: The median number of pills prescribed post-operatively decreased from 15 pills (Q1: 10, Q3: 20) to 10 pills (Q1: 8, Q3: 14.8) after implementation (p < 0.001). In the expanded-implementation cohort (293 patients), 41% patients were prescribed opioids using the GO-POP calculator. An overall median of 10 pills were prescribed with no difference by GO-POP calculator use (p = 0.26). Within the expanded-implementation cohort, refill requests (5% vs 9.2%; p = 0.26), clinician visits (0.8% vs 0.6%, p = 1), ED or urgent care visits (0% vs 2.3%, p = 0.15) and readmissions (0% vs 1.7%, p = 0.27) for pain did not differ between those prescribed opioids with and without the GO-POP calculator. Conclusions: A 33% reduction in post-operative opioid pills prescribed was seen following implementation of the GO-POP calculator into the Gynecologic Oncology division without increasing post-operative pain metrics or encounters for refill requests.

12.
J Surg Educ ; 80(10): 1424-1431, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37580240

RESUMO

OBJECTIVE: To delineate the use of gender-biased language in letters of recommendation for Obstetrics and Gynecology fellowships and its impact on applicants. DESIGN: Fellowship letters of recommendation from 4 Obstetrics and Gynecology specialties at a single institution in 2020 were included. PRIMARY OUTCOME: frequency of agentic and communal language in letters of recommendation using Linguistics Inquiry Word Count software. SECONDARY OUTCOMES: letter of recommendation length and language utilization by author gender and applicant success measured by interviews and match success. Marginal models were fit to determine if language varied by applicant and writer gender and subspecialty. Modified Poisson regression models were used to determine associations between language and interview receipt. SETTING: Single academic institution (Duke University); 2020 OB/GYN fellowship application cycle. PARTICIPANTS: A total of 1216 letters of recommendation submitted by 326 unique applicants for OB/GYN subspecialty fellowships at our institution. RESULTS: Rates of gender-biased language were low (Agentic:1.3%; communal: 0.8%). Agentic term use did not vary by applicant or author gender (p = 0.78 and 0.16) Male authors utilized 19% fewer communal terms than females (p < 0.001). Each 0.25% increase in agentic language was associated with an 18% reduction in the probability of interview invitation at our institution (p = 0.004). Percentage of agentic or communal language was not associated with successful matching into any subspecialty. CONCLUSIONS: No differences in agentic vs communal language based on applicant gender were found in this cohort, though female letter writers wrote longer letters with more communal terms. Increasing agentic terms negatively impacted interview invitation but did not affect successful matching.


Assuntos
Ginecologia , Internato e Residência , Obstetrícia , Humanos , Masculino , Feminino , Bolsas de Estudo , Obstetrícia/educação , Idioma , Sexismo , Seleção de Pessoal
13.
Front Immunol ; 14: 1205616, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37520535

RESUMO

Introduction: Assessing labial salivary gland exocrinopathy is a cornerstone in primary Sjögren's syndrome. Currently this relies on the histopathologic diagnosis of focal lymphocytic sialadenitis and computing a focus score by counting lym=phocyte foci. However, those lesions represent advanced stages of primary Sjögren's syndrome, although earlier recognition of primary Sjögren's syndrome and its effective treatment could prevent irreversible damage to labial salivary gland. This study aimed at finding early biomarkers of primary Sjögren's syndrome in labial salivary gland combining metabolomics and machine-learning approaches. Methods: We used a standardized targeted metabolomic approach involving high performance liquid chromatography coupled with mass spectrometry among newly diagnosed primary Sjögren's syndrome (n=40) and non- primary Sjögren's syndrome sicca (n=40) participants in a prospective cohort. A metabolic signature predictive of primary Sjögren's syndrome status was explored using linear (logistic regression with elastic-net regularization) and non-linear (random forests) machine learning architectures, after splitting the data set into training, validation, and test sets. Results: Among 126 metabolites accurately measured, we identified a discriminant signature composed of six metabolites with robust performances (ROC-AUC = 0.86) for predicting primary Sjögren's syndrome status. This signature included the well-known immune-metabolite kynurenine and five phospholipids (LysoPC C28:0; PCaa C26:0; PCaaC30:2; PCae C30:1, and PCaeC30:2). It was split into two main components: the first including the phospholipids was related to the intensity of lymphocytic infiltrates in salivary glands, while the second represented by kynurenine was independently associated with the presence of anti-SSA antibodies in participant serum. Conclusion: Our results reveal an immuno-lipidomic signature in labial salivary gland that accurately distinguishes early primary Sjögren's syndrome from other causes of sicca symptoms.


Assuntos
Síndrome de Sjogren , Humanos , Estudos Prospectivos , Cinurenina , Glândulas Salivares/patologia , Glândulas Salivares Menores/patologia
14.
Gynecol Oncol Rep ; 48: 101216, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37325295

RESUMO

Objective: Virtual Gynecologic Oncology fellowship recruitment has altered how candidates and programs exchange information. This study analyzes programs' web-based content and the priorities of fellowship candidates. Methods: Web-based materials of Gynecologic Oncology fellowship programs participating in the 2022 match were reviewed. An anonymous survey was emailed to applicants. Questions assessed importance of web-based materials on a Likert scale. Respondents were asked to rank factors from most to least important in their decisions to interview and rank programs. Results: Of the 66 programs participating in the 2022 Gynecologic Oncology fellowship match, 62 (93.9%) had accessible websites. Over one-fourth (25.8%) of program websites did not list application requirements. Most (74.2%) websites contained requests for letters of recommendation, but fewer (48.4%) specified the preferred quantity or authorship. Residency in-service exam score requirement information was present on 61.3% of websites. Of 100 applicants invited to participate, 44 returned surveys (44% response rate). The median number of programs applied to was 60 (IQR 51-65). Web-based materials most important to candidates were application requirements and deadlines, letter of recommendation details, and in-service exam requirements. Interaction with faculty and program information received during interview days were among the most important factors in decisions to rank programs. Conclusions: Gynecologic Oncology fellowship applicants surveyed in this study applied to nearly all participating fellowships. The content of web-based materials varies across program websites, particularly for application requirements, which applicants indicated as the most important electronically available material. Programs should have clear application requirements and provide clinical details on their websites.

15.
Gynecol Oncol ; 174: 247-252, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37243995

RESUMO

This article represents a distillation of literature to provide guidance for goals of care discussions with patients who have gynecologic malignancies. As clinicians who provide surgical care, chemotherapy, and targeted therapeutics, gynecologic oncology clinicians are uniquely positioned to form longitudinal relationships with patients that can enable patient-centered decision making. In this review, we describe optimal timing, components, and best practices for goals of care discussions in gynecologic oncology.


Assuntos
Planejamento Antecipado de Cuidados , Neoplasias dos Genitais Femininos , Assistência Terminal , Humanos , Feminino , Neoplasias dos Genitais Femininos/terapia , Tomada de Decisões , Cuidados Paliativos , Planejamento de Assistência ao Paciente , Comunicação
16.
Gynecol Oncol ; 174: 114-120, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37182431

RESUMO

OBJECTIVE: Malignancy-associated bowel obstruction (MBO) is a potential sequela of advanced gynecologic cancers, adversely impacting both quality of life and prognosis. The Henry score (HS) was developed in a gastrointestinal cancer-predominant population to predict 30-day mortality. We aim to characterize MBO in gynecologic cancers and assess the utility of the HS in this population. METHODS: This is a retrospective review of patients with gynecologic cancer and MBO admitted to a single academic institution from 2016 to 2021. The primary outcome is to characterize malignant small and large bowel obstructions in primary and recurrent gynecologic cancer using readmission and mortality rates. Secondary outcomes are to assess the Henry score and inpatient MBO management. RESULTS: 179 patients totaling 269 were admissions identified, most commonly affecting patients with ovarian cancer. The majority (89.4%) were managed non-operatively while 10.6% were managed surgically. No significant differences were observed in survival for medical versus surgical management. Thirty-day mortality increased with increasing HS (0%, 0-1; 14.3%, 2-3; 40.9%, 4-5). Over 1/3 (34.1%) of patients were readmitted for recurrent or persistent MBO. Goals of care conversations were documented for 56.8% of patients with HS 4-5. Mortality rates across the entire cohort were high-20.1% and 60.9% had died by 1 and 6 months, respectively. CONCLUSIONS: Survival rates following an initial MBO admission are poor. The HS has utility in gynecologic cancers for assessing 30-day mortality and may be a useful tool to aid in the management and counseling of patients with gynecologic cancer and MBO.


Assuntos
Neoplasias dos Genitais Femininos , Obstrução Intestinal , Neoplasias Ovarianas , Humanos , Feminino , Qualidade de Vida , Cuidados Paliativos , Recidiva Local de Neoplasia/complicações , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/terapia , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Obstrução Intestinal/etiologia , Obstrução Intestinal/terapia
17.
Cell ; 186(6): 1127-1143.e18, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36931243

RESUMO

CD8+ T cell responses are critical for anti-tumor immunity. While extensively profiled in the tumor microenvironment, recent studies in mice identified responses in lymph nodes (LNs) as essential; however, the role of LNs in human cancer patients remains unknown. We examined CD8+ T cells in human head and neck squamous cell carcinomas, regional LNs, and blood using mass cytometry, single-cell genomics, and multiplexed ion beam imaging. We identified progenitor exhausted CD8+ T cells (Tpex) that were abundant in uninvolved LN and clonally related to terminally exhausted cells in the tumor. After anti-PD-L1 immunotherapy, Tpex in uninvolved LNs reduced in frequency but localized near dendritic cells and proliferating intermediate-exhausted CD8+ T cells (Tex-int), consistent with activation and differentiation. LN responses coincided with increased circulating Tex-int. In metastatic LNs, these response hallmarks were impaired, with immunosuppressive cellular niches. Our results identify important roles for LNs in anti-tumor immune responses in humans.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Humanos , Animais , Camundongos , Linfonodos , Neoplasias/terapia , Neoplasias/patologia , Imunoterapia/métodos , Microambiente Tumoral
18.
BJOG ; 130(5): 443-453, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36648416

RESUMO

BACKGROUND: High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically reviewed. OBJECTIVES: To compile global high-risk GTN (prognostic score ≥7) cohorts to summarise treatments and outcomes by disease characteristics and primary chemotherapy. SEARCH STRATEGY: MEDLINE, Embase, Scopus, ClinicalTrials.gov and Cochrane were searched through March 2021. SELECTION CRITERIA: Full-text manuscripts reporting mortality among ≥10 high-risk GTN patients. DATA COLLECTION AND ANALYSIS: Binomial proportions were summed, and random-effects meta-analyses performed. MAIN RESULTS: From 1137 records, we included 35 studies, representing 20 countries. Among 2276 unique high-risk GTN patients, 99.7% received chemotherapy, 35.8% surgery and 4.9% radiation. Mortality was 10.9% (243/2236; meta-analysis: 10%, 95% confidence interval [CI] 7-12%) and likelihood of complete response to primary chemotherapy was 79.7% (1506/1890; meta-analysis: 78%, 95% CI: 74-83%). Across 24 reporting studies, modern preferred chemotherapy (EMA/CO or EMA/EP) was associated with lower mortality (overall: 8.8 versus 9.5%; comparative meta-analysis: 8.1 versus 12.4%, OR 0.42, 95% CI: 0.20-0.90%, 14 studies) and higher likelihood of complete response (overall: 76.6 versus 72.8%; comparative meta-analysis: 75.9 versus 60.7%, OR 2.98, 95% CI: 1.06-8.35%, 14 studies), though studies focused on non-preferred regimens reported comparable outcomes. Mortality was increased for ultra-high-risk disease (30 versus 7.5% high-risk; meta-analysis OR 7.44, 95% CI: 4.29-12.9%) and disease following term delivery (20.8 versus 7.3% following molar pregnancy; meta-analysis OR 2.64, 95% CI: 1.10-6.31%). Relapse rate estimates ranged from 3 to 6%. CONCLUSIONS: High-risk GTN is responsive to several chemotherapy regimens, with EMA/CO or EMA/EP associated with improved outcomes. Mortality is increased in patients with ultra-high-risk, relapsed and post-term pregnancy disease.


Assuntos
Doença Trofoblástica Gestacional , Mola Hidatiforme , Gravidez , Feminino , Humanos , Metotrexato , Dactinomicina/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Doença Trofoblástica Gestacional/tratamento farmacológico , Mola Hidatiforme/induzido quimicamente , Estudos Retrospectivos
19.
Gynecol Oncol ; 168: 144-150, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36442425

RESUMO

OBJECTIVE(S): Risk-stratified thromboprophylaxis is recommended for oncology patients with a Khorana risk score (KS) ≥ 2 receiving cancer-directed therapy. We describe a quality improvement (QI) initiative designed to increase adherence to thromboprophylaxis guidelines for patients with gynecologic malignancies initiating outpatient treatment. METHODS: Provider awareness and documentation of venous thromboembolism (VTE) risk assessment and thromboprophylaxis eligibility were identified as key QI drivers. Starting May 2021, a KS calculator and thromboprophylaxis algorithm were incorporated into outpatient documentation templates. Patients with gynecologic malignancies initiating outpatient therapy from January - December 2021 were eligible. The primary process measure was the percentage of patients with KS eligibility documented each month during the baseline (Jan - Apr) versus implementation (May - Dec) periods. Rate of appropriate thromboprophylaxis initiation and incidence of VTE served as outcome measures. Incidence of adverse bleeding events served as the balancing measure. RESULTS: 337 patients accounted for the initiation of 383 treatment regimens, including 128 in the baseline period and 255 in the implementation period. KS documentation increased significantly between the baseline and implementation periods (7% vs 62.4%, p < 0.001). 73 of the 177 eligible patients (46.2%; 166 unique patients) had appropriate documentation; of these, 57 initiated thromboprophylaxis. There was no difference in VTE rates or adverse bleeding events between eligible patients who initiated thromboprophylaxis compared with those who did not (12.3% vs 15.6%; p = 0.65 and 7.0% vs 8.2%; p = 1.0, respectively). CONCLUSION(S): This QI initiative resulted in greater adherence to risk-stratified thromboprophylaxis guidelines. No bleeding signals were identified. Studies addressing cost, medication adherence, and long-term outcomes are necessary.


Assuntos
Neoplasias dos Genitais Femininos , Tromboembolia Venosa , Humanos , Feminino , Anticoagulantes/efeitos adversos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/tratamento farmacológico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Melhoria de Qualidade , Hemorragia/induzido quimicamente
20.
Gynecol Oncol ; 168: 166-175, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36502783

RESUMO

OBJECTIVES: Black patients with endometrial cancer are less likely to express distress and receive referrals for support services compared to White patients. We aim to characterize patient perceptions of the National Comprehensive Cancer Network Distress Thermometer and Problem List (NCCN DT & PL), a common distress screening tool, among Black and White patients with endometrial cancer and determine strategies to improve equity in referral to appropriate support services. METHODS: We conducted semi-structured interviews with 15 Black and 15 White patients with endometrial cancer who reported varying levels of distress on the NCCN DT & PL. Interviews were audio-recorded, transcribed, evaluated through staged content analysis, and salient themes were compared by patient race. RESULTS: The NCCN DT & PL was generally considered understandable, however the word "distress" could be alienating to participants who considered their stress to be less "drastic." Black participants mentioned fewer negative emotions such as worry and sadness in describing distress and spoke more often of a positive outlook. Additionally, Black participants emphasized the importance of relationship-building with clinicians for open communication on the NCCN DT & PL and clinical encounter. Finally, participants were divided on whether they would alter the way they completed the NCCN DT & PL given more information on cut off scores for referrals, but generally expressed a desire for more direct offers of support services. CONCLUSIONS: Relationship-building, open communication around emotion, and longitudinal direct offers of support emerged as avenues to reduce inequities in referral to supportive services for patients with endometrial cancer.


Assuntos
Neoplasias do Endométrio , Neoplasias , Feminino , Humanos , Neoplasias/psicologia , Brancos , Estresse Psicológico/diagnóstico , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Detecção Precoce de Câncer , Neoplasias do Endométrio/diagnóstico , Ansiedade , Programas de Rastreamento
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