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BACKGROUND AND AIMS: The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC. APPROACH AND RESULTS: Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n = 106) and an independent validation cohort ( n = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99). CONCLUSION: HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.
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Carcinoma Hepatocelular , Vesículas Extracelulares , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Biomarcadores Tumorais/análise , Vesículas Extracelulares/química , Proteínas de Membrana , Eletrocardiografia , GlipicanasRESUMO
BACKGROUND: After treatment of pregnancy-associated breast cancer (PABC), some women desire future pregnancy. While safety of pregnancy after breast cancer has been demonstrated, the same cannot be said about women with PABC. OBJECTIVE: The aim of this study was to describe the incidence and outcomes of patients with PABC with subsequent pregnancies compared with those without another pregnancy. METHODS: A retrospective chart review identified patients diagnosed with breast cancer during pregnancy or within 5 years postpartum between 2011 and 2023. Patients were then screened for further pregnancy. Clinicopathologic variables, oncologic outcomes, and pregnancy outcomes were recorded. The Chi-square test and t-test were used to compare patients with subsequent pregnancy with those without. Kaplan-Meier method and log-rank test were used to estimate 5-year disease-free survival (DFS). RESULTS: Overall, 75 patients with PABC were identified, 58 of whom had PABC and no further pregnancies (NSP-PABC) and 17 with subsequent pregnancy (SP-PABC). Compared with patients with NSP-PABC, patients with SP-PABC were significantly younger (p = 0.015) and less likely to have prior pregnancies (p < 0.001). Overall median follow-up was 4.3 years. Calculated 5-year DFS rates were 86.2% and 89.0% for the SP-PABC and NSP-PABC groups, respectively (p = 0.76). Calculated 5-year overall survival was 100% and 90.7% for the SP-PABC and NSP-PABC groups, respectively (p = 0.22). Within the SP-PABC group, 14/17 patients had successful deliveries. CONCLUSIONS: This study provides the first descriptions of patients with PABC and subsequent pregnancy. Additional investigation, likely with pooled analysis from multiple institutions, is necessary to determine the oncologic and obstetric safety of pregnancy following PABC.
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Fluid restriction and diuretic management are mainstays in the postoperative management of cardiac patients, at risk of volume overload and its deleterious effects on primary cardiac function and multi-organ systems. The importance of fluid homeostasis is further emphasized among orthotopic heart transplant recipients (OHT). We sought to investigate the relationship between postoperative volume overload, mortality, and allograft dysfunction among pediatric OHT recipients within 1-year of transplantation. This is a retrospective cohort study from a single pediatric OHT center. Children under 21 years undergoing cardiac transplantation between 2010 and 2018 were included. Cumulative fluid overload (cFO) was assessed as percent fluid accumulation adjusted for preoperative body weight. Greater than 10% cFO defined those with postoperative cFO and a comparison of postoperative cFO vs. no postoperative cFO (< 5%) is reported. 102 pediatric OHT recipients were included. Early cFO at 72 h post-OHT occurred in 14% and overall cFO at 1-week post-OHT occurred in 23% of patients. Risk factors for cFO included younger age, lower weight, and postoperative ECMO. Early cFO was associated with postoperative mortality at 1-year, OR 8.6 (95% CI 1.4, 51.6), p = 0.04, independent of age and weight. There was no significant relationship between cFO and allograft dysfunction, measured by rates of clinical rejection and cardiopulmonary filling pressures within 1-year of transplant. Early postoperative volume overload is prevalent and associated with increased risk of death at 1-year among pediatric OHT recipients. It may be an important postoperative marker of transplant survival, and this relationship warrants further clinical investigation.
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Insuficiência Cardíaca , Transplante de Coração , Transplantes , Humanos , Criança , Estudos Retrospectivos , Insuficiência Cardíaca/etiologia , Transplante de Coração/efeitos adversos , Fatores de RiscoRESUMO
BACKGROUND: Targeting the deeper, subplatysmal structures in the neck has recently grown in popularity. In particular, interventions targeting the "bulky" anterior digastric (AD) muscle have been described with excellent results. However, much remains to be understood about the deep anatomy of the neck and the age-associated changes of the AD. OBJECTIVES: The aim of this study was to examine the relationship between AD volume and age. METHODS: This retrospective study calculated the AD volume from MRI segmentation in subjects between the ages of 20 to 92 years, scans of whom had previously been recorded. Those with compromised imaging due to pathology or artifact were excluded. Subjects were divided into 4 age-defined cohorts for clinical applicability. RESULTS: This study included 129 patients (male n = 64) with a mean age of 52.3. The AD volume of the reference group was 3.2 cm3. A linear decrease in muscle volume was observed with age compared with the reference group: 2.95 cm3 in the 45- to 54-year-old cohort (P = 0.3), 2.7 cm3 in the 55- to 64-year-old cohort (P = 0.05), and 2.45 cm3 in the >65-year-old cohort (P < 0.001). Male sex (P = 0.0001) and laterality (P = 0.003) were associated with significantly larger volumes. Overweight and obese BMI classification was not associated with a significantly different volume than normal or underweight subjects (P = 0.067). CONCLUSIONS: The study findings suggest an age-associated reduction in AD volume. Gender and laterality significantly affected volume, whereas BMI did not. Although the results do not support the theory of muscular hypertrophy with aging, they reveal that the perceived bulkiness may be due to changes in the surrounding anatomy affecting the morphology of the AD and subsequent blunting of the cervicomental angle.
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Envelhecimento , Imageamento por Ressonância Magnética , Humanos , Masculino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos Retrospectivos , Envelhecimento/fisiologia , Imageamento por Ressonância Magnética/métodos , Pescoço , MúsculosRESUMO
BACKGROUND: Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes. METHODS: This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.The pre-defined primary end point was the same-basin regional nodal recurrence, calculated using properties of binomial distribution. Time to events was calculated using the Kaplan-Meier method. The secondary end points were overall survival, progression-free survival, melanoma-specific survival (MSS), and distant metastasis-free survival (DMFS). RESULTS: For all the patients undergoing MILND, the same-basin regional recurrence rate was 4.4 % (10/228; 95 % confidence interval [CI], 2.1-7.9 %): 8.2 % (4/49) for clinical nodal disease and 3.4 % (6/179) for patients with a positive sentinel lymph node (SLN) as the indication. For the 288 patients enrolled in MSLT-II who underwent OILND for a positive SLN, 17 (5.9 %) had regional node recurrence as their first event. After controlling for ulceration, positive LN count and positive non-SLNs at the time of lymphadenectomy, no difference in OS, PFS, MSS or DMFS was observed for patients with a positive SLN who underwent MILND versus OILND. CONCLUSION: This large multi-institutional experience supports the oncologic safety of MILND for melanoma. The outcomes in this large multi-institutional experience of MILND compared favorably with those for an OILND population during similar periods, supporting the oncologic safety of MILND for melanoma.
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Melanoma , Neoplasias Cutâneas , Humanos , Excisão de Linfonodo/métodos , Melanoma/patologia , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Debate surrounding the morphological evolution of the submandibular gland (SMG) with aging, and the uncertain influence of patient demographics, has led to hesitancy about incorporating targeted interventions of the SMG into clinical practice. OBJECTIVES: The aim of this study was to determine whether SMG ptosis, hypertrophy, or both is the primary etiology behind the increase in submandibular volume with age. METHODS: MRI segmentation was used to calculate the total and inframandibular (IM) volume and height of the SMG. Adult subjects with previous MRIs of the head and neck were used for analysis. Those with pathology or artifact compromising the SMG were excluded. Subjects were divided into 4 age-defined cohorts, for clinical applicability. RESULTS: The study included 129 patients (65 females; 64 males) with a mean age of 52.3 years (range, 20-85 years). No significant change in total SMG volume was observed between the reference group and all cohorts. The IM-SMG volume of the reference cohort was 5.77 cm3. All 3 cohorts had a greater IM-SMG volume than the reference group. The 45- to 54-year cohort had a mean volume of 6.7 cm3 (Pâ =â 0.4), the 55- to 64-year cohort, 7.5 cm3 (Pâ =â 0.01), and the ≥65-year cohort, 7.2 cm3 (Pâ =â 0.01). Male sex and overweight or obese BMI were associated with significantly larger total and IM-SMG volumes. CONCLUSIONS: The novel finding of a significantly larger IM-SMG volume with no change in total volume provides evidence for SMG ptosis rather than hypertrophy as a significant contributor to age-related submandibular fullness. The lack of any significant difference in total volume or height with aging emphasizes the role of glandular descent.
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Pescoço , Glândula Submandibular , Adulto , Feminino , Humanos , Hipertrofia/diagnóstico por imagem , Hipertrofia/patologia , Masculino , Pessoa de Meia-Idade , Glândula Submandibular/diagnóstico por imagemRESUMO
Little is known about the benefits and risks of myeloid growth factor administration after chimeric antigen receptor (CAR) T-cell therapy for diffuse large B-cell lymphoma (DLBCL). We present a retrospective analysis among 22 relapsed/refractory DLBCL patients who received CAR T-cell therapy with axicabtagene ciloleucel. Filgrastim was administered by physician discretion to seven patients (31.8%), and the median duration of neutropenia after lymphodepleting therapy was significantly shorter for those patients who received filgrastim (5 vs 15 days, P = .016). Five patients (22.7%) developed infection in the 30 days post-CAR T-cell therapy with three patients being Grade 3 or higher. There was no difference in the incidence and severity of infection based on filgrastim use (P = .274, P = .138). Among the seven patients that received filgrastim, six patients (85.7%) and four patients (57.1%) had evidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), respectively. Among the 15 patients that did not receive filgrastim, 8 patients (53.3%) and 7 patients (46.7%) had evidence of CRS and ICANS, respectively. There was no significant difference in the incidence of developing CRS or ICANS between the group of patients that received filgrastim and those that did not (P = .193, P = .647). However, there was a significant increase in the severity of CRS for patients that received filgrastim compared to those that did not (P = .042). Filgrastim administration after CAR T-cell therapy may lead to an increase in severity of CRS without decreasing infection rates.
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Filgrastim/efeitos adversos , Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/terapia , Receptores de Antígenos Quiméricos/imunologia , Idoso , Síndrome da Liberação de Citocina/epidemiologia , Feminino , Humanos , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Pessoa de Meia-Idade , Síndromes Neurotóxicas/epidemiologia , Neutropenia/prevenção & controle , Estudos RetrospectivosRESUMO
BACKGROUND: Acute respiratory failure (ARF) can progress to acute respiratory distress syndrome and death. Biomarkers may allow for risk stratification and prognostic enrichment in ARF. Thrombomodulin (TM) is a transmembrane antithrombotic mediator expressed in endothelial cells. It is cleaved into its soluble form (sTM) during inflammation and vascular injury. Levels of sTM correlate with inflammation and end organ dysfunction. METHODS: This was a prospective observational study of 432 patients aged 2 weeks-17 years requiring invasive mechanical ventilation. It was ancillary to the multicenter clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE). After consent, patients had up to 3 plasma samples collected at 24-h intervals within 5 days after intubation. sTM was assayed by ELISA. The Hazard ratio (HR) for 90-day mortality was determined by Cox regression. Mixed effect models (MEM) were used to test for association with extrapulmonary multiorgan failure (MOF) and oxygenation index (OI). Age, race, sex and PRISM-III scores were used as confounding variables for multivariable analyses. RESULTS: sTM values ranged from 16.6 to 670.9 ng/ml within 5 days after intubation. Higher sTM was associated with increased 90-day mortality (n = 432, adjusted HR = 1.003, p = 0.02) and worse OI in the first 5 days after intubation (n = 252, Estimate = 0.02, p < 0.01). Both initial and slope of sTM were associated with increased extrapulmonary MOF in unadjusted and adjusted analyses (Intercept, Estimate = 0.003, p < 0.0001; and slope, Estimate = 0.01, p = 0.0009, n = 386). CONCLUSIONS: Plasma sTM is associated with mortality, severity of hypoxic respiratory failure and worsening extrapulmonary MOF in children with ARF. This suggests a role of vascular injury in the pathogenesis of ARF and provides potential applicability towards targeted therapies. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00814099 . In healthy lung endothelium, thrombomodulin (TM) recruits thrombin to activate Protein-C (PC/APC), that inhibits plasminogen activator-1 (PAI-1) and thrombosis. In inflamed and damaged endothelium, TM is cleaved into its soluble form (sTM), precluding its usual regulation of thrombosis. In this study, we measured plasma sTM levels in pediatric patients with respiratory failure and found that sTM correlated with mortality and other clinical markers of poor outcomes.
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Mortalidade/tendências , Trombomodulina/análise , Biomarcadores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos , Prognóstico , Respiração Artificial , Insuficiência RespiratóriaRESUMO
OBJECTIVE: We observed the long-term trend of Long Acting Reversible Contraception (LARC) usage before and after the 2016 presidential election. METHODS: We observed the rate of LARC dispensed at a university student health centre in the 18 months preceding and 27 months following the 2016 U.S. presidential election which posed threat to contraception access. We applied a segmented regression model using two linear regression line segments to evaluate whether there is a time point where the trend of LARC dispensing changed. We fit the regression models with a breakpoint at month 0 (election month) and 3 months with a Locally Estimated Scatterplot Smoothing (LOESS) estimate with parameters obtained by estimating simple linear regression models separately below and above the breakpoint '0'. RESULTS: There were a total of 2067 LARC methods dispensed from May 2015 to February 2019. The average number of LARC methods dispensed before November 2016 was 38/month and increased to 51/month post-presidential election. The LARC dispense rate significantly increased each month (0.38, 1.74; 95% confidence level, p < 0.05) until a breakpoint at 6 months (standard error 4.11) post-election followed by slower decrease (-0.59/month, 95% confidence level: -1.37, 0.20; p=not significant). CONCLUSION: Our study is the first to report long-term trends (27 months post-election) in LARC uptake amidst the public discourse that suggested the end of a policy that provided LARC insurance coverage. Although this observational study cannot suggest causality, the findings could reflect actions taken to prevent unintended pregnancy in response to the event of uncertain national policy.
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Anticoncepcionais Femininos/uso terapêutico , Acessibilidade aos Serviços de Saúde , Cobertura do Seguro , Contracepção Reversível de Longo Prazo/estatística & dados numéricos , Adulto , Anticoncepção , Feminino , Humanos , Políticas , Política , Gravidez , Gravidez não Planejada , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the feasibility, acceptability, and preliminary efficacy of a mind-body intervention for moderate to severe primary dysmenorrhea (PD). DESIGN: Open trial (single arm). SETTING: Academic medical school. SUBJECTS: A total of 20 young adult women with moderate to severe primary dysmenorrhea were included across four separate intervention groups. METHODS: All participants received five 90-minute sessions of a mind-body intervention and completed self-report measures of menstrual pain, depression, anxiety, somatization, and pain catastrophizing at baseline, post-treatment, and at one-, two-, three-, and 12-month follow-up. Self-report of medication use and use of skills learned during the intervention were also collected at all follow-up points. RESULTS: Participants reported significantly lower menstrual pain over time compared with baseline. No changes in anxiety, depression, or somatization were observed, although pain catastrophizing improved over time. Changes in menstrual pain were not associated with changes in medication use or reported use of skills. CONCLUSIONS: A mind-body intervention is a promising nondrug intervention for primary dysmenorrhea, and future research should focus on testing the intervention further as part of a randomized clinical trial.
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Dismenorreia , Dismenorreia/terapia , Feminino , Humanos , Medição da Dor , Adulto JovemRESUMO
OBJECTIVES: To evaluate the risk factors for mortality in pediatric extracorporeal membrane oxygenation patients. DESIGN: Retrospective, single-center study. SETTING: PICU and Pediatric cardiothoracic ICU in an urban, quaternary care center. PATIENTS: All neonatal and pediatric patients requiring extracorporeal membrane oxygenation at our institution between January 2014 and December 2018, who underwent a standardized continuous electroencephalogram neuromonitoring protocol during most of the duration of extracorporeal membrane oxygenation support. We excluded patients who had extracorporeal membrane oxygenation initiated at another institution. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Sixty-six children required extracorporeal membrane oxygenation support during this period. Four patients were excluded, three due to lack of electroencephalogram data, one with extracorporeal membrane oxygenation initiated at other institution. In the remaining 62, 11 patients (17%) had seizures, of which 5 (45%) had status epilepticus. Eight of 11 patients (72%) had exclusively electrographic seizures. A total of 33 patients (53.2%) died, of which 22 died during extracorporeal membrane oxygenation course, and one died 3 years after hospital discharge. Mean survival from extracorporeal membrane oxygenation initiation was 766.9 days (standard deviation, 691.7; median, 546.5; interquartile range 1-3, 97.7-1255.0). In multivariate analysis, increased risk of mortality was associated with the use of extracorporeal cardiopulmonary resuscitation (hazard ratio, 4.33; 95% CI, 1.75-10.72; p = 0.002), imaging findings of cerebral edema (hazard ratio, 14.31; 95% CI, 5.18-39.54; p < 0.001), high lactate level (> 100 mg/dL within 2 hr preextracorporeal membrane oxygenation) (hazard ratio, 1.22; 95% CI, 1.03-1.44; p = 0.022), and prolonged deep hypothermic circulatory arrest (hazard ratio, 3.43; 95% CI, 1.65-7.13; p < 0.001). Presence of seizures was associated with imaging findings of cerebral edema (hazard ratio, 4.16; 95% CI, 1.04-16.58; p = 0.04). CONCLUSIONS: Seizures are common in children requiring extracorporeal membrane oxygenation support, with a high rate of electrographic seizures and status epilepticus, as in prior studies. Presence of cerebral edema is both risk factor for mortality and seizures. Other risk factors for mortality include extracorporeal cardiopulmonary resuscitation, high lactate levels, and prolonged deep hypothermic circulatory arrest.
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Oxigenação por Membrana Extracorpórea , Criança , Oxigenação por Membrana Extracorpórea/efeitos adversos , Mortalidade Hospitalar , Humanos , Lactente , Prevalência , Estudos Retrospectivos , Fatores de Risco , Convulsões/diagnóstico , Convulsões/epidemiologiaRESUMO
BACKGROUND: Although only a small proportion of thin melanomas result in lymph node metastasis, the abundance of these lesions results in a relatively large absolute number of patients with a diagnosis of nodal metastases, determined by either sentinel lymph node (SLN) biopsy or clinical nodal recurrence (CNR). METHODS: Independent cohorts with thin melanoma and either SLN metastasis or CNR were identified at two melanoma referral centers. At both centers, SLN metastasis patients were included. At center 1, the CNR cohort included patients with initial negative clinical nodal evaluation followed by CNR. At center 2, the CNR cohort was restricted to those presenting in the era before the use of SLN biopsy. Uni- and multivariable analyses of melanoma-specific survival (MSS) were performed. RESULTS: At center 1, 427 CNR patients were compared with 91 SLN+ patients. The 5- and 10-year survival rates in the SLN group were respectively 88 and 84 % compared with 72 and 49 % in the CNR group (p < 0.0001). The multivariate analysis showed age older than 50 years (hazard ratio [HR] 1.5; 95 % confidence interval [CI] 1.2-1.9), present ulceration (HR 1.9; 95 % CI 1.2-2.9), unknown ulceration (HR 1.6; 95 % CI 1.3-2.1), truncal site (HR 1.6; 95 % CI 1.2-2.2), and CNR (HR 3.3; 95 % CI 1.8-6.0) to be associated significantly with decreased MSS (p < 0.01 for each). The center 2 cohort demonstrated remarkably similar findings, with a 5-year MSS of 88 % in the SLN (n = 29) group and 76 % in the CNR group (n = 39, p = 0.09). CONCLUSION: Patients with nodal metastases from thin melanomas have a substantial risk of melanoma death. This risk is lower among patients whose disease is discovered by SLN biopsy rather than CNR.
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Melanoma/patologia , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/patologia , Fatores Etários , Reações Falso-Negativas , Feminino , Humanos , Metástase Linfática , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Úlcera Cutânea/etiologia , Taxa de Sobrevida , Tronco , Carga TumoralRESUMO
BACKGROUND AND OBJECTIVES: For patients with cutaneous melanoma, primary tumors located in the head and neck is associated with poor outcomes. The reason for this difference and whether it is applicable to all locations within the head and neck remains unclear. We hypothesized that scalp melanoma is uniquely distinguished from other anatomic sites and is independently responsible for the poor prognosis of head and neck melanoma. METHODS: Query and analysis of a prospectively maintained melanoma database of all patients treated for primary cutaneous melanoma from 1971 to 2010. RESULTS: Of 11 384 patients identified, 7% (n = 799) of lesions originated on the scalp. Scalp primaries were more often found in males and were associated with increased Breslow thickness and were more frequently ulcerated compared to all other anatomic sites (P = 0.0001). On multivariate analysis, scalp location was an independent predictor of worse melanoma-specific (HR 1.75; CI 1.50-2.04; P < 0.0001) and overall survival (HR 1.62; CI 1.41-1.86; P < 0.0001). CONCLUSIONS: This, the largest series examining scalp melanoma, confirms that scalp location is independently responsible for the negative prognosis associated with head and neck melanoma. Although the pathophysiology of this difference remains to be determined, these data argue for more rigorous surveillance of this anatomic location.
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Neoplasias de Cabeça e Pescoço/patologia , Melanoma/mortalidade , Melanoma/patologia , Couro Cabeludo , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: The staging of gastric cancer has become increasingly complex. With an emerging 15-node quality measure and a revised American Joint Committee on Cancer (AJCC) staging system, we evaluated the need for more intricate staging systems to predict survival outcomes in gastric cancer. METHODS: The Surveillance, Epidemiology and End Results Program (SEER) database was used to identify 124,972 patients with gastric cancer between 2000 and 2010. Primary endpoints were 5-year disease-specific survival (DSS) and overall survival (OS). Analysis was performed on patients with ≥15 nodes evaluated. Multivariable regression with/without the inclusion of lymph node (LN) assessment and LN ratio were compared using the Akaike information criterion. RESULTS: The number of patients included in the final analysis was 12,096. The proportion of patients with an adequate lymphadenectomy increased markedly from 27 % in 2000 to 52 % in 2010. Overall 5-year DSS and OS was 61.9 and 48.8 %, respectively, for patients with ≥15 nodes examined, versus 57.7 and 39.9 %, respectively, for those with <15 sampled nodes (p < 0.0001). In patients with ≥15 nodes evaluated, the addition of LN evaluation and LN ratio to the existing staging model improved its ability to predict 5-year DSS and OS (p < 0.0001). LN evaluation and LN ratio were comparable in their ability to supplement the existing AJCC 7th edition (AJCC7) staging system. CONCLUSION: The inclusion of a minimum 15-LN quality measure improves the prognostic ability of the AJCC7 staging system, without adding significant complexity.
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Adenocarcinoma/patologia , Excisão de Linfonodo/normas , Linfonodos/patologia , Melhoria de Qualidade , Indicadores de Qualidade em Assistência à Saúde , Neoplasias Gástricas/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Programa de SEER , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Taxa de SobrevidaRESUMO
BACKGROUND: Radiotherapy (RT) reduces local recurrence after breast-conserving surgery (BCS) for breast cancer, but under-utilization of RT has been reported. Accelerated partial-breast irradiation (PBI) improves RT accessibility, but it is uncertain if this has improved RT utilization. METHODS: The Surveillance, Epidemiology and End Results registry was used to identify women who underwent BCS for stage 0 or 1 breast cancer from 2000 to 2009. Temporal trends in RT utilization and RT modality were determined. Chi-square analysis and multivariate logistic regression identified predictors of RT utilization and modality. RESULTS: Of 180,219 study patients, 131,343 (73 %) received RT; 123,703 (94 %) of RT recipients received whole-breast irradiation (WBI) and 6,251 (5 %) received PBI. PBI rates increased dramatically during the study period (0.32 % in 2000 vs. 6.5 % in 2009), but overall RT utilization remained relatively stable because of a decline in WBI (69.8 % in 2000 vs. 62.4 % in 2009). RT utilization was unchanged in rural counties, and declined for women <40 and ≥70 years of age, and for Native American, Asian and Hispanic patients. White and Black women used PBI most frequently (4 % each) and were the only race groups with improved RT utilization over time. Predictors of RT usage included age, race, marital status, tumor size, grade, hormone receptor status, lymph node evaluation, geographic region, metropolitan status, education, and employment status. CONCLUSIONS: Women who undergo RT are opting for PBI more frequently, but the increased use of this modality has not improved overall RT utilization for patients with early-stage breast cancer.
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Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Radioterapia Adjuvante/estatística & dados numéricos , População Rural , População Urbana , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , População Rural/estatística & dados numéricos , Estados Unidos/epidemiologia , População Urbana/estatística & dados numéricosRESUMO
Primary cilia are membrane-covered microtubule-based structures that protrude from the cell surface and are critical for cell signaling and homeostasis during human development and adulthood. Dysregulation of cilia formation, length, and function can lead to a spectrum of human diseases and syndromes known as ciliopathies. Although some genetic and chemical screens have been performed to define important factors that modulate cilia biogenesis and length control, there are currently no clinical treatments that restore cilia length in patients. We report that the microtubule-targeting agent MI-181(mitotic inhibitor-181) is a potent modulator of cilia length and biogenesis. Treatment of retinal pigment epithelial-1 cells with MI-181 induced an increase in the average size of cilia and in the percent ciliated cells under nonstarved conditions. Importantly, MI-181 was effective at rescuing cilia length and ciliation defects in cells that had been treated with the intraflagellar transport inhibitor Ciliobrevin D or the O-GlcNAc transferase inhibitor OSMI-1. Most importantly, MI-181 induced an increase in cilia length and restored ciliation in cells with compromised shortened cilia at low nanomolar concentrations and did not show an inhibitory response at high concentrations. Therefore, MI-181 represents a lead molecule for developing drugs targeting ciliopathies characterized by shortened cilia.
Assuntos
Cílios , Cílios/efeitos dos fármacos , Cílios/metabolismo , Humanos , Linhagem Celular , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Ciliopatias/metabolismo , Ciliopatias/patologiaRESUMO
OBJECTIVES: High-need, high-cost (HNHC) patients represent a small proportion of patients in the US, but result in disproportionately higher healthcare utilization. Teaching Internal Medicine (IM) resident trainees to provide high value care for HNHC patients is critical. We sought to improve resident attitudes and increase clinical skills associated with treating HNHC patients by creating a curriculum that leveraged the UCLA Extensivist Program, a patient-centered medical home for HNHC patients. METHODS: We developed a curriculum for PGY-2 and PGY-3 IM residents centered on caring for HNHC patients over the course of 6, 4h sessions during 1 academic year. Participants completed pre- and post-intervention surveys assessing self-rated attitudes and skills associated with caring for an HNHC patient population. RESULTS: Twenty-one IM residents completed the curriculum and 41 were in the control group. There were no statistically significant differences in assessed attitudes and skills, but there were trends of improvement, including a decrease in participants who agreed or strongly agreed they felt overwhelmed when seeing patients for posthospital discharge follow up (45.0% pre- to 41.7% post-intervention) and an increase in participants who agreed or strongly agreed they have the skills to successfully transition HNHC patients between inpatient and ambulatory settings (20.0% pre- to 33.3% post-intervention). Participants reported better understanding of resources available to HNHC patients, effective coordination of transitions of care, and comprehensive assessment of social determinants of health. CONCLUSION: A curriculum to improve resident attitudes and skills associated with caring for HNHC patients was successfully implemented in an IM program at a large academic medical center. The curriculum may be adapted for other training programs; long-term training woven throughout training may be important to significantly improve resident education on how to care for HNHC patients.
RESUMO
PURPOSE: Gay, bisexual, and other cisgender men who have sex with men, and racial minority youth are at elevated risk of acquiring HIV infection. The Adolescent Trials Network 147 recruited youth with acute/recent HIV-infection for early antiretroviral treatment. The cohort make-up is described here. METHODS: Treatment-naïve, recently identified HIV + youth, aged 12-24 years, from Los Angeles and New Orleans were recruited from community centers, clinics, social media, and a high-risk seronegative cohort (n = 1,727, the Adolescent Trials Network 149) using point-of-care assays. Acute HIV infection was determined by Fiebig staging. HIV RNA viral load (VL) and CD4 cell counts, along with demographic and behavioral data were assessed at enrollment. RESULTS: Between July 2017 and July 2021, 103 newly diagnosed youth were enrolled, initiating antiretroviral treatment within a week. Mean age was 20.8 years (standard deviation: 2.4); 90.3% identified as cis male, 83.5% were single or in casual relationships, 71.8% were gay, bisexual, and other cisgender men who have sex with men; 60.2% were Black. One-fourth (24.3%) reported homelessness ever; 10.7% within last 4 months. At enrollment, median plasma VL was 37,313 HIV RNA copies/ml (interquartile range: 5,849-126,162) and median CD4 count 445.5 cells/mm3 (interquartile range: 357-613). 40% of youth reported acute retroviral symptoms before or at enrollment. Acutely infected, seroconverting youth had the highest VL. Sexually transmitted coinfections were present at enrollment in 56% of the cohort, with syphilis being most frequent (39%). DISCUSSION: Early identification and treatment of HIV can increase positive HIV outcomes. A high sexually transmitted infection burden was present in recently HIV-infected youth. Acute retroviral symptoms were not reported by most participants, demonstrating that broad universal HIV screening is needed for identification of recent infection in youth.