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1.
Am J Epidemiol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38634618

RESUMO

Women with gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB) have excess cardiovascular disease compared to those with uncomplicated births, perhaps related to pre-pregnancy inflammation, dysmetabolism or endothelial dysfunction. We included 1238 women in the Coronary Artery Risk Development in Young Adults Study (1985-2011) with 2215 births classified according to outcomes (term, uncomplicated births were the referent). Repeated measures ANOVA estimated pre-pregnancy, post-pregnancy and biomarker change according to pregnancy outcomes, adjusted for confounders. GDM and HDP groups had higher pre-pregnancy hsCRP (+0.37 [0.08, 0.65]; +0.29 [0.04, 0.55] log mg/L), leptin (+0.29 [0.09, 0.50]; +0.37 [0.17, 0.56] log ng/ml), and lower adiponectin (-0.25 [-0.36, -0.13); -0.11 [-0.22, -0.01] log ng/ml) than those with uncomplicated births and these profiles persisted in magnitude post-pregnancy. Controlling for BMI attenuated most profiles, except lower pre-pregnancy adiponectin remained associated with GDM. PTB without HDP or GDM was related to lower pre-pregnancy hsCRP and sICAM-1 (-0.31 [-0.56, -0.06] log mg/L; -0.05 [-0.09, - 0.01] log ng/ml) and a larger leptin increase from pre- to post-pregnancy, (+0.20 [0.02, 0.37] log ng/ml). Pre-pregnancy inflammation and metabolic dysfunction contributed to GDM and HDP, perhaps due to higher BMI. PTB may be related to adverse metabolic changes post-pregnancy, though the unexpected endothelial biomarker profile warrants further study.

2.
Fetal Diagn Ther ; 51(3): 216-224, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38320542

RESUMO

INTRODUCTION: A critical component of an evidence-based reassessment of in-utero intervention for fetal aqueductal stenosis (fetal AS) is determining if the prenatal diagnosis can be accurately made at a gestational age amenable to in-utero intervention. METHODS: A multicenter, prospective, observational study was conducted through the North American Fetal Therapy Network (NAFTNet). Pregnancies complicated by severe central nervous system (CNS) ventriculomegaly (lateral ventricle diameter >15 mm) not secondary to a primary diagnosis (myelomeningocele, encephalocele, etc.) were recruited at diagnosis. Imaging and laboratory findings were recorded in an online REDCap database. After evaluation, investigators were asked to render their degree of confidence in the diagnosis of fetal AS. The prenatal diagnosis was compared to the postnatal diagnosis obtained through neonatal neuroimaging. Performance characteristics of ultrasound and magnetic resonance imaging (MRI) were calculated, as was the mean gestational age at diagnosis. RESULTS: Between April 2015 and October 2022, eleven NAFTNet centers contributed 64 subjects with severe fetal CNS ventriculomegaly. Of these, 56 had both prenatal and postnatal diagnoses recorded. Ultrasound revealed 32 fetal AS true positives, 4 false positives, 7 false negatives, and 13 true negatives, rendering a sensitivity of 0.82, a specificity of 0.76, a positive predictive value of 0.89, and a negative predictive value of 0.65. The mean gestational age at diagnosis by ultrasound was 25.5 weeks (std +/- 4.7 weeks). The proportion of agreement (true positive + true negative/n) was highest at 24 weeks gestation. For fetal MRI (n = 35), the sensitivity for fetal AS was 0.95, specificity was 0.69, positive predictive value was 0.84, and negative predictive value was 0.90. MRI was performed at 25 weeks on average. CONCLUSION: The prenatal diagnosis of fetal AS can be made with accuracy at a gestational age potentially amenable to in-utero intervention. Only 7% of subjects were incorrectly diagnosed prenatally with fetal AS by ultrasound and 11% by MRI. Diagnostic accuracy of fetal AS will likely improve with increased experience.


Assuntos
Hidrocefalia , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal , Humanos , Feminino , Estudos Prospectivos , Gravidez , Hidrocefalia/diagnóstico por imagem , Diagnóstico Pré-Natal/métodos , Imageamento por Ressonância Magnética , Doenças Fetais/diagnóstico por imagem , Doenças Fetais/diagnóstico , Idade Gestacional , Adulto , Terapias Fetais/métodos
3.
Fetal Diagn Ther ; : 1-5, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38981455

RESUMO

INTRODUCTION: Fetal aqueductal stenosis (AS) affects approximately 1:1,000 pregnancies. Obstruction of cerebral spinal fluid circulation occurs at the aqueduct of Sylvius, leading to progressive hydrocephalus and macrocephaly, which often necessitates cesarean section (CS). The purpose of this study was to describe maternal outcomes associated with fetal AS. METHODS: This study is conducted through the North American Fetal Therapy Network (NAFTNet). Subjects with a prenatal diagnosis of severe fetal central nervous system ventriculomegaly were recruited and followed longitudinally. Maternal events around the delivery of fetuses with AS were recorded and analyzed. RESULTS: Thirty-seven subjects with fetal AS confirmed by neonatal neuroimaging were analyzed. The average gestational age at delivery was 36.7 weeks. Overall, 86% were delivered by CS, and 62% of these were elective. Ninety-one percent of CSs were performed through a Pfannenstiel abdominal incision. A classical uterine incision was required in 13% of cesarean deliveries. The peripartum complication rate was 27%. CONCLUSION: Women carrying a fetus with AS were at risk for preterm birth, cesarean delivery, a classical uterine incision, and peripartum complications. These data highlight the maternal morbidity associated with fetal AS and the potential benefit of in utero therapy not only for neonatal outcomes but also for maternal outcomes.

4.
Int Urogynecol J ; 34(1): 201-209, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35403880

RESUMO

INTRODUCTION AND HYPOTHESIS: To determine the 7-day incidence and risk factors of postoperative delirium (POD) occurring after prolapse surgery in women aged ≥60 years. METHODS: A prospective study of women ≥60 years undergoing prolapse surgery at a large academic center. The primary outcome is positive Confusion Assessment Method delirium screen administered in person or by telephone at the time of hospital discharge and postoperative days 1, 3, 5, and 7. RESULTS: This analysis included 165 patients, mean ± SD age of 72.5 ± 6.1 years, with median (IQR) years of education of 13 (12-16), and baseline Modified Mini-Mental Status (3MS) Exam score of 95 (92-98). Prolapse repair type was vaginal for 70% (n=115) and laparoscopic for 30% (n=50) of patients; most under general anesthesia, 151 (92.1%). The incidence of positive delirium screen during the first week after surgery was 12.1% (n=20). Most of these participants screened positive on postoperative day 0, 8.4% (n=14). In univariate analyses, a positive screen was associated with older age and fewer education years, lower 3MS exam score, greater baseline geriatric depression scale score, and greater frailty score. Lower 3MS score was the only variable that remained significant in the final model (adjusted odds ratio 0.84, 95% CI 0.75-0.95). CONCLUSIONS: One in 12 women ≥60 years deemed eligible for discharge on the day of prolapse surgery screens positive for delirium. The 7-day POD incidence is comparable to other elective non-cardiac surgery cohorts. Given the increasing trend toward same day discharge after major prolapse surgery, more research is needed to determine the impact of universal delirium screening as part of discharge assessments.


Assuntos
Delírio , Delírio do Despertar , Prolapso de Órgão Pélvico , Humanos , Feminino , Idoso , Delírio do Despertar/complicações , Estudos Prospectivos , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Prolapso de Órgão Pélvico/cirurgia , Prolapso de Órgão Pélvico/complicações
5.
Behav Med ; 49(3): 258-270, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35057715

RESUMO

The COVID-19 vaccines are highly effective in preventing COVID-19 illness; however, pregnant people were not included in the original COVID-19 vaccine trials, with resultant conflicting recommendations from health organizations regarding vaccinations for this high-risk population. Pregnant and lactating healthcare workers (HCWs), along with people planning a pregnancy, identified as "obstetric HCWs" in our study, were among the first to make decisions regarding vaccinating themselves against COVID-19. Given that HCWs are key sources of information and access to vaccinations, this study was conducted to understand the perceptions and knowledge of obstetric HCWs regarding the COVID-19 vaccine. An electronic survey to HCWs at a tertiary care institution in Pittsburgh, PA identified 83 obstetric HCWs, of which 65 (78.3%) received at least one dose of the either the Pfizer or Moderna COVID-19 vaccine, and 18 (21.7%) had not received any doses of vaccine. Pregnancy status influenced more people not to receive than to receive the vaccine. We found that both vaccinated and non-vaccinated obstetric HCWs had accurate knowledge regarding the COVID-19 vaccine. However, compared to non-vaccinated obstetric HCWs, vaccinated obstetric HCWs tended to endorse beliefs regarding herd immunity, believed they had a higher chance of acquiring COVID-19, and felt that the COVID-19 vaccine was safe for fetuses and people who were pregnant, lactating, breastfeeding, or planning a pregnancy. This study offers insight into obstetric individuals' perceptions and knowledge of the COVID-19 vaccine, and highlights areas where additional education and outreach may help obstetric individuals make informed decisions on receiving the COVID-19 vaccine.

6.
J Urol ; 203(1): 128-136, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31361571

RESUMO

PURPOSE: To our knowledge it is unknown whether stereotactic body radiation therapy of prostate cancer is a substitute for other radiation treatments or surgery, or for expanding the pool of patients who undergo treatment instead of active surveillance. MATERIALS AND METHODS: Using SEER (Surveillance, Epidemiology, and End Results)-Medicare we identified men diagnosed with prostate cancer between 2007 and 2011. We developed physician-hospital networks by identifying the treating physician of each patient based on the primary treatment received and subsequently assigning each physician to a hospital. We examined the relative distribution of prostate cancer treatments stratified by whether stereotactic body radiation therapy was performed in a network by fitting logistic regression models with robust SEs to account for patient clustering in networks. RESULTS: We identified 344 physician-hospital networks, including 30 (8.7%) and 314 (91.3%) in which stereotactic body radiation therapy was and was not performed, respectively. Networks in which that therapy was and was not done did not differ with time in the performance of robotic and radical prostatectomy, and active surveillance (all p >0.05). The relationship with intensity modulated radiation therapy did not show any consistent temporal pattern. In networks in which it was performed less intensity modulated radiation therapy was initially done but there were similar rates in later years. Brachytherapy trends differed among networks in which stereotactic body radiation therapy was vs was not performed with a lower brachytherapy rate in networks in which stereotactic body radiation therapy was done (p=0.03). CONCLUSIONS: Surgery and active surveillance rates did not differ in networks in which stereotactic body radiation therapy was vs was not performed but when that therapy was done there was a lower brachytherapy rate. Stereotactic body radiation therapy may represent more of an alternative to brachytherapy than to active surveillance.


Assuntos
Padrões de Prática Médica/estatística & dados numéricos , Neoplasias da Próstata/radioterapia , Radiocirurgia , Idoso , Humanos , Estudos Longitudinais , Masculino , Programa de SEER , Estados Unidos
7.
Prenat Diagn ; 40(5): 585-589, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31994748

RESUMO

OBJECTIVE: Thromboelastography (TEG) is a point-of-care device used to evaluate whole blood coagulation function. The TEG is unique as a test of coagulation function in that it measures the interaction of all components of clot formation, which is different than traditional laboratory-based tests that measure isolated components of coagulation. Little is known about fetal coagulation physiology. We sought to evaluate the impact of severe fetal anemia and intrauterine transfusion (IUT) on fetal coagulation physiology by use of the TEG and to compare fetal TEG values to those of healthy neonates and adults. METHOD: One milliliter of fetal blood was collected immediately before (pre) and after (post) IUT of packed red blood cells (PRBCs). Sampling and transfusion were performed for fetal anemia due to hemolytic disease of the fetus and newborn. Samples were run in duplicate. For descriptive summary, duplicate pre-IUT and post-IUT values were averaged. Values for R (initiation of clot in minutes), K (clot firmness in minutes), angle (kinetics of clot development in degrees), and MA (maximum strength in mm) were obtained for each sample and presented using mean ± SE. Pre-IUT values for R, K, angle, and MA were compared with post-IUT values using linear mixed-effect model to account for clustering due to repeated observation from the same fetus. Pre-IUT values are compared with normal healthy term neonates and healthy adults using Wald test. The study was approved by the University of Pittsburgh Institutional Review Board (PRO14050051). RESULTS: Four fetuses underwent nine IUTs rendering 17 pre-IUT and 17 post-IUT specimens. The mean gestational age at IUT was 31 weeks 2 days (25 weeks 4 days to 35 weeks 2 days). The mean IUT volume transfused was 69 mL (30-170 mL). The mean estimated percent intravascular volume transfused was 33.4% (19%-52%). Of the four variables analyzed, only R showed a significant difference, with the initiation of clot formation being modestly delayed after transfusion by an estimated 2.87 minutes (95% CI, 0.82-4.92, P = .0480). Pre-IUT values were compared with 100 normal term neonates and 118 healthy adults. Compared with pre-IUT, only R was affected (shorter) compared with term neonates (mean ± SE = 5.46 ± 0.16 minute, P < .001) and healthy adults (mean ± SE = 6.8 ± 0.13 minute, P < .001). CONCLUSION: OTHER THAN A MODEST PROLONGATION OF CLOT FORMATION TIME, IUT OF PRBCS OF UP TO 52% OF THE ESTIMATED INTRAVASCULAR VOLUME DID NOT AFFECT FETAL COAGULATION FUNCTION BY TEG. OTHER THAN A SHORTER CLOT FORMATION TIME (R), THERE IS NO DIFFERENCE IN TEG VALUES BETWEEN ANEMIC PRETERM FETUSES AND HEALTHY TERM NEONATES AND HEALTHY ADULTS. BEYOND GENERALIZABLE KNOWLEDGE, THIS INFORMATION COULD BE EXPLOITED FOR FUTURE FETAL INTERVENTION TECHNIQUES.


Assuntos
Coagulação Sanguínea/fisiologia , Transfusão de Sangue Intrauterina , Eritroblastose Fetal/sangue , Eritroblastose Fetal/terapia , Transfusão de Eritrócitos , Sangue Fetal/fisiologia , Tromboelastografia , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Gravidez
8.
BJU Int ; 123(6): 968-975, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30758125

RESUMO

OBJECTIVES: To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies. PATIENTS AND METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients diagnosed with muscle-invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis. RESULTS: Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+ , or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder-sparing approach. The adjusted probability of receiving palliative care did not significantly change over time. CONCLUSIONS: Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease-specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician-, patient-, and system-level barriers to this care.


Assuntos
Cuidados Paliativos/estatística & dados numéricos , Neoplasias da Bexiga Urinária/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Utilização de Instalações e Serviços , Feminino , Humanos , Masculino , Programa de SEER , Fatores Socioeconômicos , Tempo para o Tratamento , Estados Unidos , Neoplasias da Bexiga Urinária/patologia
9.
Cancer ; 123(15): 2945-2954, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28301689

RESUMO

BACKGROUND: Several new prostate cancer treatments have emerged since 2000, including 2 radiotherapies with similar efficacy at the time of their introduction: intensity-modulated radiotherapy (IMRT) and stereotactic body radiation therapy (SBRT). The objectives of this study were to compare their early adoption patterns and identify factors associated with their use. METHODS: By using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, patients who received radiation therapy during the 5 years after IMRT introduction (2001-2005) and the 5 years after SBRT introduction (2007-2011) were identified. The outcome of interest was the receipt of new radiation therapy (ie, IMRT or SBRT) compared with the existing standard radiation therapies at that time. The authors fit a series of multivariable, hierarchical logistic regression models accounting for patients nested within health service areas to examine the factors associated with the receipt of new radiation therapy. RESULTS: During 2001 to 2005, 5680 men (21%) received IMRT compared with standard radiation (n = 21,555). Men who received IMRT were older, had higher grade tumors, and lived in more populated areas (P < .05). During 2007 through 2011, 595 men (2%) received SBRT compared with standard radiation (n = 28,255). Men who received ng SBRT were more likely to be white, had lower grade tumors, lived in more populated areas, and were more likely to live in the Northeast (P < .05). Adjusting for cohort demographic and clinical factors, the early adoption rate for IMRT was substantially higher than that for SBRT (44% vs 4%; P < .01). CONCLUSIONS: There is a stark contrast in the adoption rates of IMRT and SBRT at the time of their introduction. Further investigation of the nonclinical factors associated with this difference is warranted. Cancer 2017;123:2945-54. © 2017 American Cancer Society.


Assuntos
Neoplasias da Próstata/terapia , Radiocirurgia/estatística & dados numéricos , Radioterapia de Intensidade Modulada/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Humanos , Modelos Logísticos , Masculino , Medicare , Análise Multivariada , Gradação de Tumores , Neoplasias da Próstata/patologia , Programa de SEER , Estados Unidos
10.
Cancer ; 122(20): 3199-3206, 2016 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-27379732

RESUMO

BACKGROUND: There are several effective treatments for prostate cancer. To what extent a patient's functional status influences the treatment decision is unknown. This study examined the association between functional status and treatment among older men with prostate cancer. METHODS: Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data were used to identify men who were 65 years old or older and were diagnosed with prostate cancer between 1998 and 2009. The primary outcome was treatment choice: conservative management, surgery, or radiation within 1 year of the diagnosis. The exposure was the functional status assessed as 4 measures within 3 domains: 1) physical function (activities of daily living [ADLs] and physical component summary score), 2) cognitive function (survey completer: self vs proxy), and 3) emotional well-being (mental component summary score). A multivariate, multinomial logistic regression was fitted with adjustments for several patient, tumor, and regional characteristics. RESULTS: This study identified 508 conservative management patients, 195 surgery patients, and 603 radiation patients. Compared with men with no ADL dependency, those with any ADL dependency had lower odds of receiving surgery (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.38-0.99) or radiation (OR, 0.58; 95% CI, 0.43-0.78) versus conservative management. ADL dependency did not differ when surgery and radiation were compared. Patients with a proxy survey response were less likely to receive surgery or radiation versus conservative management. CONCLUSIONS: Functional status is associated with treatment choice for men with prostate cancer. Future research should examine whether this is due to physician recommendations, patient preferences, or a combination. Cancer 2016;122:3199-206. © 2016 American Cancer Society.


Assuntos
Atividades Cotidianas , Comportamento de Escolha , Medicare Part C/estatística & dados numéricos , Preferência do Paciente , Neoplasias da Próstata/terapia , Idoso , Seguimentos , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/psicologia , Programa de SEER , Estados Unidos/epidemiologia , Conduta Expectante
11.
Ann Surg ; 261(1): 144-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24670844

RESUMO

OBJECTIVE: National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 was a randomized controlled trial of neoadjuvant chemoradiotherapy in patients with resectable stage II-III rectal cancer. We hypothesized that patients who underwent abdominoperineal resection (APR) would have a poorer quality of life than those who underwent sphincter-sparing surgery (SSS). METHODS: To obtain patient-reported outcomes (PROs) we administered two symptom scales at baseline and 1 year postoperatively: the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and the European Organization for the Research and Treatment of Cancer module for patients with Colorectal Cancer Quality of Life Questionnaire (EORTC QLQ-CR38). Scoring was stratified by nonrandomly assigned definitive surgery (APR vs SSS). Analyses controlled for baseline scores and stratification factors: age, sex, stage, intended surgery, and randomly assigned chemoradiotherapy. RESULTS: Of 1,608 randomly assigned patients, 987 had data for planned analyses; 62% underwent SSS; 38% underwent APR. FACT-C total and subscale scores were not statistically different by surgery at 1 year. For the EORTC QLQ-CR38 functional scales, APR patients reported worse body image (70.3 vs 77.0, P = 0.0005) at 1 year than did SSS patients. Males undergoing APR reported worse sexual enjoyment (43.7 vs 54.7, P = 0.02) at 1 year than did those undergoing SSS. For the EORTC QLQ-CR38 symptom scale scores, APR patients reported worse micturition symptoms than the SSS group at 1 year (26.9 vs 21.5, P = 0.03). SSS patients reported worse gastrointestinal tract symptoms than did the APR patients (18.9 vs 15.2, P < 0.0001), as well as weight loss (10.1 vs 6.0, P = 0.002). CONCLUSIONS: Symptoms and functional problems were detected at 1 year by EORTC QLQ-CR38, reflecting different symptom profiles in patients who underwent APR than those who underwent SSS. Information from these PROs may be useful in counseling patients anticipating surgery for rectal cancer.


Assuntos
Adenocarcinoma/cirurgia , Qualidade de Vida , Neoplasias Retais/cirurgia , Abdome/cirurgia , Adenocarcinoma/patologia , Canal Anal/cirurgia , Imagem Corporal , Feminino , Gastroenteropatias/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Períneo/cirurgia , Complicações Pós-Operatórias , Estudos Prospectivos , Neoplasias Retais/patologia , Disfunções Sexuais Fisiológicas/etiologia , Resultado do Tratamento , Transtornos Urinários/etiologia
12.
Endocr Relat Cancer ; 31(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38614127

RESUMO

Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease affecting almost exclusively female-sexed individuals. The cysts represent regions of lung destruction caused by smooth muscle tumors containing mutations in one of the two tuberous sclerosis (TSC) genes. mTORC1 inhibition slows but does not stop LAM advancement. Furthermore, monitoring disease progression is hindered by insufficient biomarkers. Therefore, new treatment options and biomarkers are needed. LAM cells express melanocytic markers, including glycoprotein non-metastatic melanoma protein B (GPNMB). The function of GPNMB in LAM is currently unknown; however, GPNMB's unique cell surface expression on tumor versus benign cells makes GPNMB a potential therapeutic target, and persistent release of its extracellular ectodomain suggests potential as a serum biomarker. Here, we establish that GPNMB expression is dependent on mTORC1 signaling, and that GPNMB regulates TSC2-null tumor cell invasion in vitro. Further, we demonstrate that GPNMB enhances TSC2-null xenograft tumor growth in vivo, and that ectodomain release is required for this xenograft growth. We also show that GPNMB's ectodomain is released from the cell surface of TSC2-null cells by proteases ADAM10 and 17, and we identify the protease target sequence on GPNMB. Finally, we demonstrate that GPNMB's ectodomain is present at higher levels in LAM patient serum compared to healthy controls and that ectodomain levels decrease with mTORC1 inhibition, making it a potential LAM biomarker.


Assuntos
Biomarcadores Tumorais , Linfangioleiomiomatose , Glicoproteínas de Membrana , Linfangioleiomiomatose/metabolismo , Linfangioleiomiomatose/patologia , Linfangioleiomiomatose/genética , Humanos , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Animais , Biomarcadores Tumorais/metabolismo , Feminino , Camundongos , Linhagem Celular Tumoral , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo , Proliferação de Células
13.
Nat Commun ; 14(1): 670, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36810851

RESUMO

In the long-lived naked mole-rat (NMR), the entire process of oogenesis occurs postnatally. Germ cell numbers increase significantly in NMRs between postnatal days 5 (P5) and P8, and germs cells positive for proliferation markers (Ki-67, pHH3) are present at least until P90. Using pluripotency markers (SOX2 and OCT4) and the primordial germ cell (PGC) marker BLIMP1, we show that PGCs persist up to P90 alongside germ cells in all stages of female differentiation and undergo mitosis both in vivo and in vitro. We identified VASA+ SOX2+ cells at 6 months and at 3-years in subordinate and reproductively activated females. Reproductive activation was associated with proliferation of VASA+ SOX2+ cells. Collectively, our results suggest that highly desynchronized germ cell development and the maintenance of a small population of PGCs that can expand upon reproductive activation are unique strategies that could help to maintain the NMR's ovarian reserve for its 30-year reproductive lifespan.


Assuntos
Oogênese , Reserva Ovariana , Animais , Feminino , Diferenciação Celular , Células Germinativas , Mitose , Ovário , Ratos-Toupeira
14.
Ann Epidemiol ; 71: 9-14, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35462044

RESUMO

PURPOSE: The incidence of Endometrial cancer (EC) has grown substantially in Asia over the past decade. However, few studies have addressed risk factors associated with EC incidence in Asian populations. We explored the association between reproductive and dietary risk factors and EC in the Singapore Chinese Health Study (SCHS), one of the largest prospective cohort studies in Asia. METHODS: Data were collected from 34,028 ethnically Chinese women aged 45-74 residing in Singapore, enrolled between 1993 and 1998. Baseline demographic, dietary, and reproductive factors were collected via structured questionnaires. EC cases were identified from the Singapore Cancer Registry (n = 126) up to 2010. Cox proportional hazard models were used to analyze association between EC and personal, reproductive, and dietary factors. RESULTS: The incidence of EC in this population was 28.8 per 100,000 person-years. Regardless of menopausal status, obesity (BMI ≥ 27) was associated with increased EC risk (HR = 2.22, 95% CI 1.26-3.92), while later age at menarche was associated with decreased EC risk (HR = 0.14, 95% CI 0.04-0.46). In postmenopausal women, later age at menopause was associated with increased EC risk (HR = 2.82, 95% CI 1.24-6.43). Lifestyle and nutritional factors were not associated with risk of EC in this cohort. CONCLUSIONS: This study is one of the largest cohort studies exploring EC risk factors in Asian populations. Our study identified similarities in EC risk factors for European and Asian populations, which potentially suggests that strategies developed for EC prevention in Western populations can be potentially appropriate for the Singapore Chinese population due to risk factor similarities.


Assuntos
Neoplasias do Endométrio , China/epidemiologia , Estudos de Coortes , Neoplasias do Endométrio/epidemiologia , Feminino , Humanos , Estudos Prospectivos , Fatores de Risco , Singapura/epidemiologia
15.
Eur J Obstet Gynecol Reprod Biol ; 259: 140-145, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33667895

RESUMO

OBJECTIVE: Hysterectomy is one of the most common surgical procedures. Same-day discharge (SDD) is increasingly utilized for minimally invasive hysterectomies, but its uptake varies across healthcare systems and surgical specialties. An evidence-based initiative was developed to aid in the incorporation of SDD into the practice of minimally invasive hysterectomy (MIH) in the UPMC Health System. The objective of this study was to identify trends of SDD utilization across various gynecologic specialties at UPMC, as well as evaluate the impact of SDD on length of stay (LOS) and complications after the implementation of SDD initiative. STUDY DESIGN: We retrospectively identified 5554 patients who underwent MIH between 2014 and 2017 and were eligible for SDD, as determined by physicians and authorized by patients' insurance plans. Multivariable logistic regression models evaluated the trend of SDD utilization among four specialty types (general gynecologists, urogynecologists, specialized minimally invasive surgeons, and oncologists) and trends in complications. Multivariable logistic and linear regression models were applied to compare complications and LOS between patients with SDD vs. those with overnight admissions. RESULTS: SDD utilization increased from 28.55% to 74.99% during the study period. SDD significantly increased over the study period for all specialty types, with urogynecologists having the highest uptake from 3.9% in 2014 to 95.8% in 2017 (p<.01). After adjusting for year, specialty types, MIH procedure type, and total case time, SDD utilization was associated with shorter mean LOS (p<.01); such that mean LOS was 764.43 min (95% CI: 735.46-793.40) for SDD patients and 2041.84 min (95% CI: 2015.99-2067.70) for patients with overnight admissions. SDD was also associated with 42% lower odds (95% CI: 0.37-0.93, p=.02) of complications compared with patients with overnight admissions. CONCLUSION: Same-day discharge uptake increased over years and was associated with lower odds of complications and decreased length of stay. More studies are needed to explore same-day discharge process to improve patient outcomes, patient satisfaction, and value of care.


Assuntos
Laparoscopia , Alta do Paciente , Feminino , Humanos , Histerectomia/efeitos adversos , Tempo de Internação , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
16.
Urol Oncol ; 39(10): 731.e17-731.e24, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33676849

RESUMO

OBJECTIVES: To quantify the proportion of patients receiving high-intensity end-of-life care, identify associated risk factors, and assess how receipt of palliative care impact end-of-life care; as the delivery of such care, and how it relates to palliative care, has not been reported in bladder cancer SUBJECTS AND METHODS: We conducted a retrospective cohort study of patients with bladder cancer who died within 1 year of diagnosis using Surveillance, Epidemiology, and End Results linked Medicare data. The primary outcome was a composite measure of high-intensity end-of-life care (>1 hospital admission, >1 ED visit, or ≥1 ICU admission within the last month of life; receipt of chemotherapy within the last 2 weeks of life; or acute care in-hospital death). Secondary outcomes included the use of such care over time and any association with the use of palliative care. A generalized linear mixed model assessed for independent determinants. RESULTS: Overall, 45% of patients received high-intensity end-of-life care. This proportion decreased over time. Patients receiving high-intensity care had higher rates of comorbidities, advanced bladder cancer, and nonbladder cancer cause of death. These patients more often received palliative care but, compared to those not receiving high-intensity care, this occurred farther removed from bladder cancer diagnosis and closer to death. CONCLUSIONS: Nearly half of Medicare beneficiaries with bladder cancer who die within 1 year of diagnosis receive high-intensity care at the end of life. Palliative care was seldom used and only very near the time of death.


Assuntos
Cuidados Paliativos/métodos , Neoplasias da Bexiga Urinária/terapia , Idoso , Feminino , Humanos , Masculino , Medicare , Análise de Sobrevida , Assistência Terminal/métodos , Estados Unidos , Neoplasias da Bexiga Urinária/mortalidade
17.
Ann Surg Oncol ; 17(4): 959-66, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20082144

RESUMO

BACKGROUND: The objective of this study is to conduct a pooled analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) colon trials involving surgery and surgery plus 5-fluorouracil and leucovorin (5-FU/LV) to compare survival and establish a baseline from which to evaluate future studies. METHODS: All patients enrolled in NSABP adjuvant trials C-01 through C-05 with stage II and III disease who were treated with surgery or with surgery plus 5-FU/LV were examined for overall survival (OS), disease-free survival (DFS), and recurrence-free interval (RFI). Time-to-event by treatment group was examined using adjusted Kaplan-Meier estimates and multivariable Cox regression analysis. RESULTS: There were 2,966 eligible patients: 693 (23%) surgery and 2,273 (77%) surgery plus 5-FU/LV; 1,255 (42%) stage II and 1,711 (58%) stage III. Age > or =60 years [hazard ratio (HR) = 1.36, P < 0.0001], male gender (HR = 1.20, P = 0.0012), and more nodes positive or fewer nodes examined (P < 0.0001) were associated with worse survival. At 5 years, the adjusted OS was 0.62 [confidence interval (CI) = 0.60-0.63] in the surgery group and 0.76 (CI = 0.74-0.78) in the surgery plus 5-FU/LV group. Treatment with 5-FU/LV was associated with improved outcome compared with surgery: OS (HR = 0.62, P < 0.0001), DFS (HR = 0.66, P < 0.0001) and RFI (HR = 0.64, P < 0.0001). Improved OS with adjuvant treatment was seen in both stage II (HR = 0.58, 95% CI = 0.48-0.71) and stage III disease (HR = 0.65, 95% CI = 0.55-0.75). CONCLUSIONS: This analysis demonstrates that treatment of colon cancer patients with 5-FU/LV following surgery provides benefit over surgery alone and can provide anticipated survival outcomes with which to compare modern adjuvant trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/mortalidade , Neoplasias do Colo/terapia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Procedimentos Cirúrgicos Operatórios , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
18.
Cancer Med ; 9(20): 7388-7397, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32813321

RESUMO

BACKGROUND: Intraperitoneal/intravenous chemotherapy (IP/IV) was associated with improved survival for ovarian cancer (OC) patients in several randomized clinical trials. However, the uptake of IP/IV in clinical practice is varied due to conflicting evidence about its impact on survival and recurrence. The aim of this study was to explore the uptake of IP/IV treatment and to evaluate its impact on survival and recurrence in OC patients. METHODS: Demographic and clinical information on OC patients (N = 2916) who underwent treatment for OC between 2000 and 2017 was obtained from the large healthcare system cancer registry. Duplicate records, grade 1, rare (eg, gelatinous carcinoma), and non-epithelial (eg, granulosa cell carcinoma) tumors were excluded. Kaplan-Meier survival curves were constructed to compare 5- and 10-year survival based on the chemotherapy type, surgery type, and stage. Multivariable Gray's piecewise constant time-varying coefficient models were fitted to evaluate the effect of IP/IV on adjusted hazard ratio (AHR) of OC survival and recurrence adjusting for potential confounders. RESULTS: The final sample consisted of 1846 OC patients, 14% (250/1846) of which received IP/IV chemotherapy. IP/IV was significantly associated with improved 10-year survival (P < .001). Multivariable Gray's model demonstrated that IP/IV therapy significantly reduced the AHR of death (AHR = 0.39-1.07, P < .001) with the beneficial effect gradually declining over time. Use of IP/IV chemotherapy had no impact on OC recurrence. CONCLUSIONS: These findings demonstrated that only a small fraction of eligible patients underwent IP/IV chemotherapy. We report a significant 10-year survival, but not necessarily recurrence benefit is associated with IP/IV chemotherapy compared to IV only, suggesting the need for novel ways of identifying patients who may benefit from IP/IV chemotherapy.


Assuntos
Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Administração Intravenosa , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Terapia Combinada , Feminino , Mortalidade Hospitalar , Humanos , Injeções Intraperitoneais , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/epidemiologia , Modelos de Riscos Proporcionais , Sistema de Registros , Programa de SEER , Resultado do Tratamento
19.
Obstet Gynecol ; 136(1): 129-139, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32541286

RESUMO

OBJECTIVE: To investigate whether women with early pregnancy elevated blood pressure (BP) or stage 1 hypertension exhibit increased risk of preeclampsia and maternal or neonatal morbidity. METHODS: We conducted a clinical cohort study of 18,162 women who delivered a singleton neonate from 2015 to 2018 and attended at least two prenatal appointments before 20 weeks of gestation. Data were collected within the Magee Obstetric Maternal and Infant database, an aggregate of prenatal and delivery health records. Early pregnancy BP was defined as average BP before 20 weeks of gestation, and women were classified with normal, elevated BP, stage 1 or 2 hypertension according to current guidelines. The primary outcome was preeclampsia. Secondary outcomes were severe maternal morbidity, placental abruption, gestational diabetes, and composite neonatal morbidity. RESULTS: Overall, 75.2% of the women were categorized with normal BP, 13.9% with elevated BP, 5.4% with stage 1 hypertension, and 5.5% with stage 2 hypertension. Risk of preeclampsia increased in a stepwise fashion with increasing BP category, adjusted for covariates (normal BP, 4.7%, referent; elevated BP, 7.3%, adjusted odds ratio [aOR] 1.29, 95% CI 1.07-1.56; stage 1, 12.3%, aOR 2.35, 95% CI 1.86-2.96), and stage 2, 30.2%, aOR 6.49, 95% CI 5.34-7.89). Results were similar among black and white women. Gestational diabetes was more prevalent among women with stage 1 (11.4%; aOR 1.50, 95% CI 1.18-1.91] and stage 2 hypertension (14.2%; aOR 1.65, 95% CI 1.30-2.10). Severe maternal morbidity and neonatal morbidity were increased only among women with stage 2 hypertension (aOR 2.99, 95% CI 2.26-3.99, and aOR 2.67, 95% CI 2.28-3.12, respectively). CONCLUSION: Women with elevated BP, and stage 1 and 2 hypertension in early pregnancy are at increased risk for preeclampsia. These findings emphasize the importance of applying the 2017 BP guidelines to reproductive-aged women. Strategies to incorporate these guidelines into obstetric care may also be warranted.


Assuntos
Pressão Sanguínea , Hipertensão Induzida pela Gravidez/epidemiologia , Adulto , Determinação da Pressão Arterial , Estudos de Coortes , Feminino , Humanos , Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/mortalidade , Hipertensão Induzida pela Gravidez/prevenção & controle , Pennsylvania/epidemiologia , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Gravidez , Resultado da Gravidez , Diagnóstico Pré-Natal , Fatores de Risco
20.
Female Pelvic Med Reconstr Surg ; 26(2): 92-96, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31990794

RESUMO

OBJECTIVES: There is limited literature regarding outcomes after sacrocolpopexy mesh removal. We sought to compare the proportion of prolapse recurrence in women after sacrocolpopexy mesh removal with women who underwent sacrocolpopexy without subsequent mesh removal. We hypothesize that more women will experience prolapse recurrence after mesh removal. METHODS: This is a retrospective cohort study of women who underwent sacrocolpopexy mesh removal between 2010 and 2019. These patients were time matched with women who had a sacrocolpopexy but did not undergo mesh removal. Prolapse recurrence was defined as the leading edge past the hymen or retreatment. Analysis was done using χ, Wilcoxon rank-sum, or t test with a Cox proportional hazard model to assess the association between mesh removal and time to recurrence. RESULTS: We identified 26 mesh removals, which were matched with 78 patients without mesh removal. The most common indications for mesh removal were exposure (69.2%) and pain (57.7%). Women who underwent mesh removal were more likely to have Mersilene mesh (19.2% vs 1.3%, P = 0.006). Recurrence occurred in 46% of women who had mesh removal compared with 7.7% in those without (P < 0.001). When adjusted for age, parity, menopause, smoking, and diabetes status, those who had mesh removal had a 15 times higher hazard of prolapse recurrence (adjusted hazard ratio = 15.4, 95% confidence interval = 4.3-54.8, P = <.0001). CONCLUSIONS: When compared with time-matched controls, women who underwent sacrocolpopexy mesh removal had a significantly higher proportion of prolapse recurrence. Prospective studies are needed to further explore the utility of concomitant prolapse repair at the time of mesh removal.


Assuntos
Remoção de Dispositivo/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia , Prolapso de Órgão Pélvico , Complicações Pós-Operatórias/cirurgia , Telas Cirúrgicas/efeitos adversos , Idoso , Remoção de Dispositivo/métodos , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/instrumentação , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Prolapso de Órgão Pélvico/diagnóstico , Prolapso de Órgão Pélvico/cirurgia , Complicações Pós-Operatórias/etiologia , Recidiva , Projetos de Pesquisa , Estudos Retrospectivos
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