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1.
Artigo em Inglês | MEDLINE | ID: mdl-38816189

RESUMO

BACKGROUND: Understanding the sequential progression of cognitive impairments in Parkinson's disease (PD) is crucial for elucidating neuropathological underpinnings, refining the assessment of PD-related cognitive decline stages and enhancing early identification for targeted interventions. The first aim of this study was to use an innovative event-based modeling (EBM) analytic approach to estimate the sequence of cognitive declines in PD. The second aim was to validate the EBM by examining associations with EBM-derived individual-specific estimates of cognitive decline severity and performance on independent cognitive screening measures. METHODS: This cross-sectional observational study included 99 people with PD who completed a neuropsychological battery. Individuals were classified as meeting the criteria for mild cognitive impairment (PD-MCI) or subtle cognitive decline by consensus. An EBM was constructed to compare cognitively healthy individuals with those with PD-MCI or subtle cognitive disturbances. Multivariable linear regression estimated associations between the EBM-derived stage of cognitive decline and performance on two independent cognitive screening tests. RESULTS: The EBM estimated that tests assessing executive function and visuospatial ability become abnormal early in the sequence of PD-related cognitive decline. Each higher estimated stage of cognitive decline was associated with approximately 0.24 worse performance on the Dementia Rating Scale (p<0.001) and 0.26 worse performance on the Montreal Cognitive Assessment (p<0.001) adjusting for demographic and clinical variables. CONCLUSION: Findings from this study will have important clinical implications for practitioners, on specific cognitive tests to prioritise, when conducting neuropsychological evaluations with people with PD. Results also highlight the importance of frontal-subcortical system disruption impacting executive and visuospatial abilities.

2.
Ann Plast Surg ; 91(6): 679-685, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37856209

RESUMO

BACKGROUND: Tissue expanders in breast reconstruction are traditionally placed retropectoral. Increasingly, patients are undergoing prepectoral placement. The impact of this placement on the initiation of adjuvant treatment is unknown. METHODS: A retrospective review was conducted to identify women diagnosed with breast cancer who underwent mastectomy followed by radiation and/or chemotherapy. Women were divided into 3 groups: prepectoral tissue expander placement, retropectoral tissue expander placement, and no immediate reconstruction. A treatment delay was defined as greater than 8 weeks between tissue expander placement and adjuvant therapy. RESULTS: Of 634 women, 205 (32%) underwent tissue expander placement, and 429 (68%) did not have immediate reconstruction. Of those with tissue expanders placed, 84 (41%) had prepectoral placement, and 121 (59%) had retropectoral placement. The median time to adjuvant therapy was 49 days for the entire cohort: no reconstruction, 47 days; prepectoral, 57 days; and retropectoral, 55 days. Treatment delays were observed in 34% of women: no reconstruction, 28%; prepectoral, 51%; and retropectoral, 46% ( P < 0.001). Tissue expander placement was associated with a delay to adjuvant therapy when compared with no reconstruction ( P < 0.001). The location of the tissue expander did not impact the odds of having a delay. On multivariable analysis, having reconstruction, having postoperative infection, not undergoing chemotherapy treatment, and being a current smoker were associated with a delay to adjuvant therapy. A delay to treatment was not associated with worse survival. CONCLUSIONS: Placement of a tissue expander delayed adjuvant therapy. The location of tissue expander placement, retropectoral versus prepectoral, did not impact the time to adjuvant treatment.


Assuntos
Implantes de Mama , Neoplasias da Mama , Mamoplastia , Humanos , Feminino , Neoplasias da Mama/cirurgia , Mastectomia , Dispositivos para Expansão de Tecidos , Terapia Combinada , Estudos Retrospectivos , Complicações Pós-Operatórias/cirurgia
3.
Ann Surg Oncol ; 29(2): 1327-1333, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34625880

RESUMO

BACKGROUND: For locally advanced esophageal squamous cell carcinoma (ESCC), chemoradiation (ChemoRT) followed by surgery offers the best chance of cure, with a 35-50% pathologic complete response (pCR) rate. Given the morbidity of esophagectomy and the possibility of pCR with ChemoRT, a 'watch and wait' strategy has been proposed, particularly for squamous cell carcinoma. The ability to accurately predict which patients will have pCR from ChemoRT is critical in treatment decision making. This study assessed positron emission tomography (PET) in predicting pCR after neoadjuvant ChemoRT for ESCC. METHODS: ESCC patients treated with ChemoRT followed by surgery were identified. Maximum standard uptake value (SUV), metabolic tumor volume, total lesion glycolysis, and first-order textual features of standard deviation, kurtosis and skewness were measured from PET. Univariable and multivariable generalized linear method analyses were performed. A metabolic complete response (mCR) was defined as a post-therapy PET scan with maximum SUV < 4.0. RESULTS: Twenty-seven patients underwent ChemoRT followed by surgery, with overall pCR seen in 11 (41%) patients and radiographic mCR seen in 12 (44%) patients. Final pathology for these 12 patients revealed pCR (ypT0N0M0) in 5 (42%) patients and persistent disease in 7 (58%) patients. Univariate analysis did not reveal PET parameters predictive of pCR. CONCLUSION: Treatment of ESCC with ChemoRT often results in a robust clinical response. Among patients with an mCR after ChemoRT, disease persistence was found in 58%. The inability of PET to predict pCR is important in the context of a 'watch and wait' strategy for ESCC treated with ChemoRT.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Quimiorradioterapia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia , Fluordesoxiglucose F18 , Humanos , Terapia Neoadjuvante , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/uso terapêutico , Estudos Retrospectivos
4.
Ann Surg Oncol ; 29(12): 7716-7724, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35810226

RESUMO

BACKGROUND: The extent of residual disease after neoadjuvant chemotherapy (NAC) can be quantified by the Residual Cancer Burden (RCB), a prognostic tool used to estimate survival outcomes in breast cancer. This study investigated the association between RCB and locoregional recurrence (LRR). METHODS: The study reviewed 532 women with breast cancer who underwent NAC between 2010 and 2016. Relapse in the ipsilateral breast, skin/subcutis at the surgical site, chest wall, pectoralis, or regional lymph nodes defined an LRR. The LRR cumulative incidence (LRCI) was estimated using the Fine and Gray competing-risks model, with death and distant recurrence defined as competing events. The association of LRCI with prognostic variables was evaluated. RESULTS: Overall, 5.5% of the patients experienced an LRR after a median follow-up period of 65 months. The 5-year LRCI rates by RCB were as follows: RCB-0 (0.9%), RCB-1 (3.2%), RCB-2 (6.0%), and RCB-3 (12.9%). In the univariable analysis, LRCI varied significantly by RCB (p = 0.010). The multivariable analysis showed a significant association of LRCI with increasing RCB, and the patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) phenotype were at lower risk for LRR than those with HER2+ and triple-negative cancers (p < 0.032). The patients with RCB-3 were at a higher risk for local relapse than those with RCB-0 (hazard ratio, 13.78; confidence interval, 2.25-84.45; p = 0.04). Type of operation (p = 0.04) and use of adjuvant radiation (p = 0.046) were statistically significant in the multivariable model. CONCLUSIONS: The study results demonstrate a significant association between LRCI and increasing RCB, although distant recurrence is a substantial driver of disease outcomes. Future prospective studies should examine the role of RCB in clinical decisions regarding indications for adjuvant therapy.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Estudos Prospectivos , Receptor ErbB-2/metabolismo
5.
Ann Surg Oncol ; 29(13): 8060-8069, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35980548

RESUMO

BACKGROUND: The residual cancer burden class informs survival outcomes after neoadjuvant chemotherapy. We evaluated the prognostic ability of the RCB for survival outcomes in women with different phenotypic subtypes of breast cancer treated with neoadjuvant chemotherapy. Additional variables were assessed for inclusion with the RCB to further improve the model's discriminative ability. PATIENTS AND METHODS: We conducted a retrospective review of patients completing at least 75% of the recommended cycles of neoadjuvant chemotherapy between 1 January 2010 and 31 December 2016. Phenotypic subtypes were defined by hormone receptor and human epidermal growth factor receptor 2 (HER2) status at diagnosis, classified as HR+/HER2-, HER2+, or triple-negative breast cancer (TNBC). The RCB class was calculated and survival endpoints of overall survival, recurrence-free survival, and distant recurrence-free survival were analyzed using Kaplan-Meier and Cox proportional hazards methods. The discriminative ability of the models was quantified by Harrell's C-index. RESULTS: Overall, 532 women met the inclusion criteria. Median follow-up was 65 months. In univariate models, RCB was significantly associated with OS, RFS, and DRFS. The RCB class had good discriminative ability for OS, RFS, and DRFS survival, with Harrell's C-indices of 0.68, 0.67, and 0.68, respectively. The RCB class discriminated well for each survival endpoint within HER2+ and TNBC, but did not discriminate well for HR+/HER2- (OS Harrell's C-indices of 0.77, 0.75, and 0.52, respectively). CONCLUSIONS: The RCB class was prognostic for OS, RFS, and DRFS after neoadjuvant chemotherapy, but prognostic discrimination between patients with subtype HR+/HER2- was not observed during the follow-up period for which the overall event rate was low.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Terapia Neoadjuvante , Neoplasias da Mama/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasia Residual/tratamento farmacológico , Receptor ErbB-2/metabolismo , Prognóstico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante
6.
Ann Surg Oncol ; 29(5): 3291-3301, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35015183

RESUMO

BACKGROUND: Prognostic nomograms for patients with resected extremity soft tissue sarcoma (STS) include the Sarculator and Memorial Sloan Kettering (MSKCC) nomograms. We sought to validate these two nomograms within a large, modern, multi-institutional cohort of resected primary extremity STS patients. METHODS: Resected primary extremity STS patients from 2000 to 2017 were identified across nine high-volume U.S. institutions. Predicted 5- and 10-year overall survival (OS) and distant metastases cumulative incidence (DMCI), and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated with Sarculator and MSKCC nomograms, respectively. Predicted survival probabilities stratified in quintiles were compared in calibration plots to observed survival assessed by Kaplan-Meier estimates. Cumulative incidence was estimated for DMCI. Harrell's concordance index (C-index) assessed discriminative ability of nomograms. RESULTS: A total of 1326 patients underwent resection of primary extremity STS. Common histologies included: undifferentiated pleomorphic sarcoma (35%), fibrosarcoma (13%), and leiomyosarcoma (9%). Median tumor size was 8.0 cm (IQR 4.5-13.0). Tumor grade distribution was: Grade 1 (13%), Grade 2 (9%), Grade 3 (78%). Median OS was 172 months, with estimated 5- and 10-year OS of 70% and 58%. C-indices for 5- and 10-year OS (Sarculator) were 0.72 (95% CI 0.70-0.75) and 0.73 (95% CI 0.70-0.75), and 0.72 (95% CI 0.69-0.75) for 5- and 10-year DMCI. C-indices for 4-, 8-, and 12-year DSS (MSKCC) were 0.71 (95% CI 0.68-0.75). Calibration plots showed good prognostication across all outcomes. CONCLUSIONS: Sarculator and MSKCC nomograms demonstrated good prognostic ability for survival and recurrence outcomes in a modern, multi-institutional validation cohort of resected primary extremity STS patients. External validation of these nomograms supports their ongoing incorporation into clinical practice.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Extremidades/patologia , Extremidades/cirurgia , Humanos , Nomogramas , Prognóstico , Sarcoma/patologia , Neoplasias de Tecidos Moles/cirurgia
7.
BMC Pregnancy Childbirth ; 22(1): 344, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35448967

RESUMO

BACKGROUND: Most existing evidence about the prevalence of prenatal cannabis use relies on self-reported measures, which is limited by social desirability bias and recall bias. To date, several studies have examined the validity of self-reported measures of prenatal cannabis use, but this evidence has yet to be synthesized. To address this gap, we performed a scoping review to systematically identify and synthesize existing evidence on the validity of self-reported measures of cannabis use among pregnant women. METHODS: We searched PubMed, PyschINFO, CINAHL, Cochrane/CENTRAL, and Google Scholar for peer-reviewed studies published in English between January 2010 and June 2021. We included studies that compared self-reported measures of cannabis use to a biochemical measure of cannabis (e.g., urine, hair, meconium) in pregnant women. We excluded studies reporting solely on prenatal cannabis use prevalence as well as those that examined self-reported drug use in which cannabis use was not a distinct category. RESULTS: We found 12 unique studies (11 primary studies and one systematic review) that examined the validity of self-reported prenatal cannabis use, compared to a biochemical sample. Most studies were conducted in the US and conducted in either a hospital or clinical setting. We found that self-report was more valid in populations with a current or prior history of drug use. Self-report was also more valid when assessed via interviews by research team members than health care provider screenings or self-administered surveys. The most commonly used biochemical measure used was urine drug testing, which was found to have the highest level of concordance with self-report. CONCLUSIONS: This scoping review systematically mapped existing evidence on the validity of self-reported prenatal cannabis use. Although much remains unknown in this area, an important next step is a systematic review that would provide robust evidence on clinical utilization of self-reported use in conjunction with biochemical samples. Further research is needed to examine validity by type of measure and mode of administration. Additionally, future studies could assess factors associated with disclosure of use across different critical maternal health periods beyond pregnancy.


Assuntos
Cannabis , Transtornos Relacionados ao Uso de Substâncias , Feminino , Humanos , Recém-Nascido , Masculino , Saúde Materna , Mecônio , Gravidez , Gestantes , Autorrelato
8.
BMC Womens Health ; 22(1): 95, 2022 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-35346156

RESUMO

BACKGROUND: Cannabis use among women of reproductive age has increased substantially in recent decades. Understanding reasons for cannabis use in this population is critical for cannabis use prevention efforts. Thus, this scoping review aimed to identify and synthesize current measures on reasons for cannabis use in women of reproductive age. METHODS: We searched PubMed, PyschINFO, CINAHL, and Google Scholar for relevant studies published in English between January 2010 and April 2021. Peer-reviewed, quantitative studies reporting on measures of cannabis-related knowledge, attitudes, perceptions, motivations, and influences among women of reproductive age were eligible for inclusion. We excluded studies not focused on women of reproductive age and studies reporting cannabis use prevalence data only. RESULTS: We included 11 studies (10 primary studies and 1 review) with varying subpopulation samples of women, including non-pregnant women (n = 2), women experiencing infertility (n = 1), pregnant women (n = 4), postpartum women (n = 3), and women in the perinatal period (n = 1). Measurement topic areas included information received from health care professionals, attitudes, perceptions and experiences about cannabis use, knowledge of potential harms, and motivations for cannabis use. Most studies including measures of risk perceptions were conducted among pregnant or postpartum women (n = 4). A single study measured influences of cannabis use; no studies measured social or peer influences of use. Most studies (n = 7) created their own measures, with 2 studies using secondary data via measures from population-based surveillance systems in the United States, and one using a previously validated instrument. Recommendations for future research were centered around addressing knowledge gaps of health effects of cannabis use across different time periods, and etiology of cannabis use. CONCLUSIONS: We found vast measurement gaps in current measures of antecedents of cannabis use among women of reproductive age, providing clear direction for future research in this area. Findings necessitate psychometric evaluation of existing measures to ascertain validity and reliability, as well as development of additional measures of women's cannabis-related attitudes, perceptions, motivations, and influences. This work is critical to guide not only epidemiologic studies, but cannabis-related prevention work as well.


Assuntos
Cannabis , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Motivação , Grupo Associado , Gravidez , Reprodutibilidade dos Testes , Estados Unidos
9.
J Minim Invasive Gynecol ; 29(11): 1248-1252, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35940525

RESUMO

STUDY OBJECTIVE: To determine the effect of the coronavirus disease 2019 (COVID-19) pandemic on the rate of same-day discharge (SDD) after minimally invasive surgery for endometrial cancer. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENTS: A total of 166 patients underwent a minimally invasive surgery procedure for the indication of endometrial cancer at a large academic institution from September 1, 2019, to October 1, 2020-80 patients before the implementation of the COVID-19 restrictions and 86 patients after. INTERVENTIONS: COVID-19 pandemic with visitor restrictions and hospital policy changes placed on March 17, 2020. MEASUREMENTS AND MAIN RESULTS: SDD rate was increased by 18% after the start of the COVID-19 pandemic (40% vs 58%, p = .02). There were no differences between the 2 groups with regard to operative time (p = .07), estimated blood loss (p = .21), uterine weight (p = .12), age (p = .06), body mass index (p = .42), or surgery start time (p = .15). In a multivariable logistic regression model, subjects in the COVID-19 group had 3.08 times (95% confidence interval, 1.40-6.74; p = .01) higher odds of SDD than those in the pre-COVID-19 group. There was no difference in 30-day readmission rates (7.5% vs 5.8%, p = .66). CONCLUSION: There was a significant increase in the SDD of patients with endometrial cancer since the start of the COVID-19 pandemic. The pandemic has strained hospital resources and motivated patients and physicians to avoid hospitalization. This shows that with proper motivation, an increase in SDD rates is possible without an increase in complications or rehospitalization.


Assuntos
COVID-19 , Neoplasias do Endométrio , Laparoscopia , Feminino , Humanos , Alta do Paciente , COVID-19/epidemiologia , Estudos Retrospectivos , Pandemias , Laparoscopia/métodos , Neoplasias do Endométrio/cirurgia , Complicações Pós-Operatórias/epidemiologia
10.
Neurobiol Learn Mem ; 183: 107461, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34015445

RESUMO

Episodic memory involves binding stimuli and/or events together in time and place. Furthermore, memories become more complex when new experiences influence the meaning of stimuli within the original memory. Thus collectively, complex episodic memory formation and maintenance involves processes such as encoding, storage, retrieval, updating and reconsolidation, which can be studied using animal models of higher-order conditioning. In the present study aversive and appetitive sensory preconditioning paradigms were used to test the hypothesis that the postrhinal cortex (POR), which is a component of the hippocampal memory system, is involved in higher-order conditioning. Drawing on the known role of the POR in contextual learning, Experiment 1 employed a four-phase sensory preconditioning task that involved fear learning and context discrimination in rats with or without permanent lesions of the POR. In parallel, to examine POR function during higher-order conditioning in the absence of a particular spatial arrangement, Experiments 2 and 3 used a three-phase sensory preconditioning paradigm involving phasic stimuli. In Experiment 2, bilateral lesions of the POR were made and in Experiment 3, a chemogenetic approach was used to temporarily inactivate POR neurons during each phase of the paradigm. Evidence of successful sensory preconditioning was observed in sham rats which, during the critical context discrimination test, demonstrated higher levels of freezing behavior when re-exposed to the paired versus the unpaired context, whereas POR-lesioned rats did not. Data from the appetitive sensory preconditioning paradigm also confirmed the hypothesis in that during the critical auditory discrimination test, sham rats showed greater food cup responding following presentations of the paired compared to the unpaired auditory stimulus, whereas POR-lesioned rats did not. Lastly, in Experiment 3, when the POR was inactivated only during preconditioning or only during conditioning, discrimination during the critical auditory test was impaired. Thus, regardless of whether stimulus-stimulus associations were formed between static or phasic stimuli or whether revaluation of the paired stimulus occurred through association with an aversive or an appetitive unconditioned stimulus, the effects were the same; POR lesions disrupted the ability to use higher-order conditioned stimuli to guide prospective behavior.


Assuntos
Aprendizagem por Associação/fisiologia , Aprendizagem por Discriminação/fisiologia , Consolidação da Memória , Memória Episódica , Giro Para-Hipocampal/fisiologia , Animais , Comportamento Apetitivo , Aprendizagem da Esquiva , Condicionamento Clássico/fisiologia , Medo , Estimulação Física/métodos , Ratos
11.
Mov Disord ; 36(5): 1126-1136, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33470460

RESUMO

BACKGROUND: The glymphatic system, including the perivascular space (PVS), plays a critical role in brain homeostasis. Although mounting evidence from Alzheimer's disease has supported the potential role of PVS in neurodegenerative disorders, its contribution in Parkinson's disease (PD) has not been fully elucidated. Although idiopathic (IPD) and familial PD (FPD) share similar pathophysiology in terms of protein aggregation, the differential impact of PVS on PD subtypes remains unknown. Our objective was to examine the differences in PVS volume fraction in IPD and FPD compared to healthy controls (HCs) and nonmanifest carriers (NMCs). METHODS: A total of 470 individuals were analyzed from the Parkinson's Progression Markers Initiative database, including (1) IPD (n = 179), (2) FPD (LRRK2 [leucine-rich repeat kinase 2], glucocerebrosidase, or α-synuclein) (n = 67), (3) NMC (n = 101), and (4) HCs (n = 84). Total PVS volume fraction (%) was compared using parcellation and quantitation within greater white matter volume at global and regional levels in all cortical and subcortical white matter. RESULTS: There was a significant increase in global and regional PVS volume fraction in PD versus non-PD, particularly in FPD versus NMC and LRRK2 FPD versus NMC. Regionally, FPD and NMC differed in the medial orbitofrontal region, as did LRRK2 FPD versus NMC. Non-PD and PD differed in the medial orbitofrontal region and the banks of the superior temporal regions. IPD and FPD differed in the cuneus and lateral occipital regions. CONCLUSIONS: Our findings support the role of PVS in PD and highlight a potentially significant contribution of PVS to the pathophysiology of FPD, particularly LRRK2. © 2021 International Parkinson and Movement Disorder Society.


Assuntos
Sistema Glinfático , Doença de Parkinson , Sistema Glinfático/metabolismo , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Mutação , Doença de Parkinson/genética , alfa-Sinucleína/metabolismo
12.
J Surg Oncol ; 124(5): 829-837, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34254691

RESUMO

BACKGROUND AND OBJECTIVES: Prognostic nomograms for patients undergoing resection of retroperitoneal sarcoma (RPS) include the Sarculator and Memorial Sloan Kettering (MSK) sarcoma nomograms. We sought to validate the Sarculator and MSK nomograms within a large, modern multi-institutional cohort of patients with primary RPS undergoing resection. METHODS: Patients who underwent resection of primary RPS between 2000 and 2017 across nine high-volume US institutions were identified. Predicted 7-year disease-free (DFS) and overall survival (OS) and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated from the Sarculator and MSK nomograms, respectively. Nomogram-predicted survival probabilities were stratified in quintiles and compared in calibration plots to observed survival outcomes assessed by Kaplan-Meier estimates. Discriminative ability of nomograms was quantified by Harrell's concordance index (C-index). RESULTS: Five hundred and two patients underwent resection of primary RPS. Histologies included leiomyosarcoma (30%), dedifferentiated liposarcoma (23%), and well-differentiated liposarcoma (15%). Median tumor size was 14.0 cm (interquartile range [IQR], 8.5-21.0 cm). Tumor grade distribution was: Grade 1 (27%), Grade 2 (17%), and Grade 3 (56%). Median DFS was 31.5 months; 7-year DFS was 29%. Median OS was 93.8 months; 7-year OS was 51%. C-indices for 7-year DFS, and OS by the Sarculator nomogram were 0.65 (95% confidence interval [CI]: 0.62-0.69) and 0.69 (95%CI: 0.65-0.73); plots demonstrated good calibration for predicting 7-year outcomes. The C-index for 4-, 8-, and 12-year DSS by the MSK nomogram was 0.71 (95%CI: 0.67-0.75); plots demonstrated similarly good calibration ability. CONCLUSIONS: In a diverse, modern validation cohort of patients with resected primary RPS, both Sarculator and MSK nomograms demonstrated good prognostic ability, supporting their ongoing adoption into clinical practice.


Assuntos
Nomogramas , Neoplasias Retroperitoneais/patologia , Sarcoma/patologia , Procedimentos Cirúrgicos Operatórios/mortalidade , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Sarcoma/cirurgia , Taxa de Sobrevida
13.
Pharm Stat ; 20(3): 563-572, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33484036

RESUMO

Response-adaptive (RA) allocation designs can skew the allocation of incoming subjects toward the better performing treatment group based on the previously accrued responses. While unstable estimators and increased variability can adversely affect adaptation in early trial stages, Bayesian methods can be implemented with decreasingly informative priors (DIP) to overcome these difficulties. DIPs have been previously used for binary outcomes to constrain adaptation early in the trial, yet gradually increase adaptation as subjects accrue. We extend the DIP approach to RA designs for continuous outcomes, primarily in the normal conjugate family by functionalizing the prior effective sample size to equal the unobserved sample size. We compare this effective sample size DIP approach to other DIP formulations. Further, we considered various allocation equations and assessed their behavior utilizing DIPs. Simulated clinical trials comparing the behavior of these approaches with traditional Frequentist and Bayesian RA as well as balanced designs show that the natural lead-in approaches maintain improved treatment with lower variability and greater power.


Assuntos
Projetos de Pesquisa , Teorema de Bayes , Humanos , Tamanho da Amostra
14.
Hum Genet ; 139(3): 333-356, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31677133

RESUMO

Although aging is a conserved phenomenon across evolutionary distant species, aspects of the aging process have been found to differ between males and females of the same species. Indeed, observations across mammalian studies have revealed the existence of longevity and health disparities between sexes, including in humans (i.e. with a female or male advantage). However, the underlying mechanisms for these sex differences in health and lifespan remain poorly understood, and it is unclear which aspects of this dimorphism stem from hormonal differences (i.e. predominance of estrogens vs. androgens) or from karyotypic differences (i.e. XX vs. XY sex chromosome complement). In this review, we discuss the state of the knowledge in terms of sex dimorphism in various aspects of aging and in human age-related diseases. Where the interplay between sex differences and age-related differences has not been explored fully, we present the state of the field to highlight important future research directions. We also discuss various dietary, drug or genetic interventions that were shown to improve longevity in a sex-dimorphic fashion. Finally, emerging tools and models that can be leveraged to decipher the mechanisms underlying sex differences in aging are also briefly discussed.


Assuntos
Envelhecimento/fisiologia , Animais , Humanos , Longevidade/fisiologia , Caracteres Sexuais
17.
Laryngoscope ; 134(5): 2262-2268, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37983884

RESUMO

OBJECTIVE: Patients undergoing laryngectomy are particularly vulnerable to postoperative complications secondary to social and nutritional barriers, substance abuse, and prior cancer treatment. Enhanced Recovery After Surgery (ERAS) programs may mitigate this vulnerability and improve postoperative complications and oncologic outcomes. The objective of this study is to evaluate the postoperative complication rate and oncologic outcomes of patients undergoing laryngectomy before and after ERAS program implementation. METHODS: A historic cohort of 50 patients who underwent laryngectomy at the Levine Cancer Institute, Charlotte, North Carolina from 2014 to 2019 (pre-ERAS) was compared to 33 patients who underwent laryngectomy after ERAS implementation from 2019 to 2020. The primary outcomes included length of stay (LOS), Clavien-Dindo postoperative complications through 30 days following discharge, overall survival (OS), and recurrence-free survival between pre-ERAS and ERAS groups. RESULTS: Demographic characteristics between the two groups were similar. ERAS pathway implementation led to core care element consistency and improvement in the clinical perioperative course, including preoperative nutritional intervention (p = 0.009), postoperative ventilator independence (p = 0.0004), and refractory nausea/emesis (p = 0.18). Severe (≥ grade 3) complications (p = 0.49) and LOS (p = 0.68) were similar between groups. No significant difference in Cox proportional modeling of OS (p = 0.60) or recurrence-free survival (p = 0.17) was noted. CONCLUSIONS: ERAS did not improve LOS, major postoperative complications, or oncologic outcomes in this cohort of patients who underwent laryngectomy. However, ERAS positively influenced secondary endpoints within the laryngectomy perioperative course, conferring qualitative health care benefits. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2262-2268, 2024.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Humanos , Laringectomia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Cuidados Pré-Operatórios , Tempo de Internação , Estudos Retrospectivos , Assistência Perioperatória
18.
Brain Imaging Behav ; 18(1): 57-65, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37855955

RESUMO

Perivascular spaces (PVS), fluid-filled compartments surrounding brain vasculature, are an essential component of the glymphatic system responsible for transport of waste and nutrients. Glymphatic system impairment may underlie cognitive deficits in Parkinson's disease (PD). Studies have focused on the role of basal ganglia PVS with cognition in PD, but the role of white matter PVS is unknown. This study examined the relationship of white matter and basal ganglia PVS with domain-specific and global cognition in individuals with PD. Fifty individuals with PD underwent 3T T1w magnetic resonance imaging (MRI) to determine PVS volume fraction, defined as PVS volume normalized to total regional volume, within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of global cognitive function (Montreal Cognitive Assessment, and global cognitive composite score), and cognitive-specific domains (executive function, memory, visuospatial function, attention, and language). Higher white matter rostral middle frontal PVS was associated with lower scores in both global cognitive and visuospatial function. In the basal ganglia higher PVS was associated with lower scores for memory with a trend towards lower global cognitive composite score. While previous reports have shown that greater amount of PVS in the basal ganglia is associated with decline in global cognition in PD, our findings suggest that increased white matter PVS volume may also underlie changes in cognition.


Assuntos
Sistema Glinfático , Doença de Parkinson , Substância Branca , Humanos , Doença de Parkinson/complicações , Substância Branca/patologia , Sistema Glinfático/diagnóstico por imagem , Sistema Glinfático/patologia , Imageamento por Ressonância Magnética/métodos , Cognição , Gânglios da Base/diagnóstico por imagem
19.
Brain Behav ; 14(7): e3607, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39010690

RESUMO

BACKGROUND: Pathologic perivascular spaces (PVS), the fluid-filled compartments surrounding brain vasculature, may underlie cognitive decline in Parkinson's disease (PD). However, whether this impacts specific cognitive domains has not been investigated. OBJECTIVES: This study examined the relationship of PVS volume at baseline with domain-specific and global cognitive change over 2 years in PD individuals. METHODS: A total of 39 individuals with PD underwent 3T T1w magnetic resonance imaging to determine PVS volume fraction (PVS volume normalized to total regional volume) within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, and superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of cognitive domains and global cognitive function at baseline and after 2 years. RESULTS: Higher basal ganglia PVS at baseline was associated with greater decline in attention, executive function, and global cognition scores. CONCLUSIONS: While previous reports have associated elevated PVS volume in the basal ganglia with decline in global cognition in PD, our findings show such decline may affect the attention and executive function domains.


Assuntos
Atenção , Gânglios da Base , Disfunção Cognitiva , Função Executiva , Imageamento por Ressonância Magnética , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/patologia , Gânglios da Base/fisiopatologia , Função Executiva/fisiologia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Atenção/fisiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Sistema Glinfático/diagnóstico por imagem , Sistema Glinfático/patologia , Sistema Glinfático/fisiopatologia , Testes Neuropsicológicos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/fisiopatologia
20.
Curr Oncol ; 30(2): 2482-2492, 2023 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-36826150

RESUMO

The National Surgical Quality Improvement Project (NSQIP) dataset was used to identify perioperative variables associated with the length of stay (LOS) and early discharge among cancer patients undergoing colectomy. Patients who underwent non-emergent right colectomy for colon cancer from 2012 to 2019 were identified from the NSQIP and colectomy-targeted databases. Postoperative LOS was analyzed based on postoperative day (POD) of discharge, with patients grouped into Early Discharge (POD 0-2), Standard Discharge (POD 3-5), or Late Discharge (POD ≥ 6) cohorts. Multivariable ordinal logistic regression was performed to identify risk factors associated with early discharge. The NSQIP query yielded 26,072 patients: 3684 (14%) in the Early Discharge, 13,414 (52%) in the Standard Discharge, and 8974 (34%) in the Late Discharge cohorts. The median LOS was 4.0 days (IQR: 3.0-7.0). Thirty-day readmission rates were 7% for Early Discharge, 8% for Standard Discharge, and 12% for Late Discharge. On multivariable regression analysis, risk factors significantly associated with a shorter LOS included independent functional status, minimally invasive approach, and absence of ostomy or additional bowel resection (all p < 0.001). Perioperative variables can be used to develop a model to identify patients eligible for early discharge after right colectomy for colon cancer. Efforts to decrease the overall median length of stay should focus on optimization of modifiable risk factors.


Assuntos
Neoplasias do Colo , Melhoria de Qualidade , Humanos , Alta do Paciente , Estudos Retrospectivos , Colectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia
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