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INTRODUCTION: Acute necrotizing pancreatitis (ANP) complicates up to 15% of acute pancreatitis cases. ANP has historically been associated with a significant risk for readmission, but there are currently no studies exploring factors that associate with risk for unplanned, early (<30-day) readmissions in this patient population. METHODS: We performed a retrospective review of all consecutive patients presenting to hospitals in the Indiana University (IU) Health system with pancreatic necrosis between December 2016 and June 2020. Patients younger than 18 years of age, without confirmed pancreatic necrosis and those that suffered in-hospital mortality were excluded. Logistic regression was performed to identify potential predictors of early readmission in this group of patients. RESULTS: One hundred and sixty-two patients met study criteria. 27.7% of the cohort was readmitted within 30-days of index discharge. The median time to readmission was 10 days (IQR 5-17 days). The most frequent reason for readmission was abdominal pain (75.6%), followed by nausea and vomiting in (35.6%). Discharge to home was associated with 93% lower odds of readmission. We found no additional clinical factors that predicted early readmission. CONCLUSION: Patients with ANP have a significant risk for early (<30 days) readmission. Direct discharge to home, rather than short or long-term rehabilitation facilities, is associated with lower odds of early readmission. Analysis was otherwise negative for independent, clinical predictors of early unplanned readmissions in ANP.
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Pancreatitis Aguda Necrotizante , Readmisión del Paciente , Humanos , Pancreatitis Aguda Necrotizante/terapia , Enfermedad Aguda , Factores de Riesgo , Estudios RetrospectivosRESUMEN
An expert panel was convened to provide insight and guidance on per- and polyfluoroalkyl substances (PFAS) grouping for the purposes of protecting human health from drinking water exposures, and how risks to PFAS mixtures should be assessed. These questions were addressed through multiple rounds of blind, independent responses to charge questions, and review and comments on co-panelists responses. The experts agreed that the lack of consistent interpretations of human health risk for well-studied PFAS and the lack of information for the vast majority of PFAS present significant challenges for any mixtures risk assessment approach. Most experts agreed that "all PFAS" should not be grouped together, persistence alone is not sufficient for grouping PFAS for the purposes of assessing human health risk, and that the definition of appropriate subgroups can only be defined on a case-by-case manner. Most panelists agreed that it is inappropriate to assume equal toxicity/potency across the diverse class of PFAS. A tiered approach combining multiple lines of evidence was presented as a possible viable means for addressing PFAS that lack analytical and/or toxicological studies. Most PFAS risk assessments will need to employ assumptions that are more likely to overestimate risk than to underestimate risk, given the choice of assumptions regarding dose-response model, uncertainty factors, and exposure information.
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Ácidos Alcanesulfónicos , Agua Potable , Fluorocarburos , Agua Potable/análisis , Fluorocarburos/análisis , Fluorocarburos/toxicidad , Humanos , Medición de Riesgo , IncertidumbreRESUMEN
BACKGROUND AND AIMS: Endoscopic stenting is the standard of care for full thickness esophageal wall defects. The aim of this study is to evaluate outcomes of endoscopic closure of esophageal defects using stenting, with or without endoscopic suturing. METHODS: This is a single-center retrospective study of patients with esophageal wall defects who underwent endoscopic interventions. Outcomes of stenting with or without endoscopic suturing of the defect were assessed. Univariate and multivariate logistic regression models were used to examine factors associated with successful defect closure. RESULTS: One hundred and fourteen patients with esophageal wall defects underwent 254 endoscopies with an overall complete closure rate of 75.8%. Twenty-three (20.2%) patients underwent primary closure using endoscopic suturing and subsequent esophageal stenting, while 91 (79.8%) underwent esophageal stenting only. The dual modality group (versus the stent-only group) had similar defect closure rates (84.2 vs. 73.8%, p = 0.55) and time to stent migration (37 vs. 12.5 days, p = 0.07), but was associated with longer procedure times (60 vs. 36 min, p < 0.01) and fewer additional endoscopic procedures (13.6 vs. 43.2%, p = 0.01). Stent suturing significantly decreased migration (35.5 vs. 58.5%, p = 0.04), was associated with fewer additional endoscopies (15.4 vs. 50%, p < 0.01) and reduced need for additional stents (7.7 vs. 34.3%, p < 0.01). On multivariate analysis, chronic defects (> four weeks old) were 81% less likely to close compared to acute (≤ 4 weeks) defects (OR 0.19, CI 0.04-0.77, p = 0.02), and large diameter stents (23 mm) were associated with higher odds of defect closure (OR 3.36, CI 1.02-11.4, p = 0.04). CONCLUSION: Endoscopic treatment of esophageal wall defects is safe, effective, and more likely to be successful in acute defects using larger caliber stents. Stent suturing reduces migration, need for additional endoscopic procedures, and stent exchanges. Further comparative studies with larger cohorts are needed to validate our results.
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Esófago , Suturas , Esófago/cirugía , Humanos , Estudios Retrospectivos , Stents , Resultado del TratamientoRESUMEN
BACKGROUND: Psychiatric problems among college students on USA campuses are common. Little is known about similar problems in developing countries, particularly the Arab region. The goal of this study was to assess the frequency of selected psychiatric problems among college students in two Arab countries: Qatar and Lebanon, and to compare them to the USA. METHODS: The Healthy Minds Study, an online confidential survey of common psychiatric symptoms designed for college campuses was used. We used the Patient Health Questionnaire-9 (PHQ-9) to screen for major depression, the Generalized Anxiety Disorder-7 (GAD-7) to screen for generalized anxiety and the SCOFF questionnaire to screen for eating disorders. Comparisons were made using ANOVA, Chi-Square tests and logistic regressions. RESULTS: A total of 1841 students participated in the study. The rates of depression (PHQ-9 ≥ 12), generalized anxiety (GAD-7 ≥ 10) and eating disorders (SCOFF≥3) at the combined Arab universities were 34.6, 36.1 and 20.4% respectively. The corresponding rates in the USA were: 12.8, 15.9 and 6.8% (p < 0.001 for all measures). The impact of psychiatric problems on functioning in general and academic performance in particular was more severe in the Arab countries compared to the USA (p < 0.001). Independent predictors of psychiatric problems in general included location, female gender, financial difficulties and poor grades. Being religious had a protective association with mental health. CONCLUSION: The rates of depression, anxiety and eating disorders were significantly higher among college students in Qatar and Lebanon compared to the USA. Additional research is needed to determine whether these results reflect methodological limitations or true differences in psychopathology across these populations. If replicated, the results indicate that the psychiatric problems on college campuses in the USA are a microcosm of a global problem that needs global solutions.
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Trastornos de Ansiedad , Trastorno Depresivo Mayor , Trastornos de Alimentación y de la Ingestión de Alimentos , Estudiantes , Adolescente , Adulto , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/epidemiología , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Etnopsicología/métodos , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Femenino , Humanos , Líbano/epidemiología , Masculino , Salud Mental/estadística & datos numéricos , Escalas de Valoración Psiquiátrica , Qatar/epidemiología , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Encuestas y Cuestionarios , Universidades/estadística & datos numéricosRESUMEN
This study was designed to evaluate markers of systemic oxidative stress and lung histopathology following subacute exposure to geogenic dust with varying heavy metal content collected from a natural setting prone to wind erosion and used heavily for off-road vehicle recreation. Adult female B6C3F1 mice were exposed to several concentrations of dust collected from seven different types of surfaces at the Nellis Dunes Recreation Area in Clark County, Nevada, designated here as CBN 1-7. Dust representing each of the seven surface types, with an average median diameter of 4.2 µm, was selected and administered via oropharyngeal aspiration to mice at concentrations from 0.01 to 100 mg of dust kg(-1) of body weight. Exposures were given four times spaced a week apart over a 28 day period to mimic a month of weekend exposures. Lung pathology was evaluated while plasma markers of oxidative stress included levels of reactive oxygen and nitrogen species, superoxide dismutase, total antioxidant capacity and total glutathione. Overall, results of these assays to evaluate markers of oxidative stress indicate that no single CBN surface type was able to consistently induce markers of systemic oxidative stress at a particular dose or in a dose-response manner. All surface types were able to induce some level of lung inflammation, typically at the highest exposure levels. These data suggest that dust from the Nellis Dunes Recreation Area may present a potential health risk, but additional studies are necessary to characterize the full extent of health risks to humans. Copyright © 2016 John Wiley & Sons, Ltd.
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Polvo/análisis , Exposición por Inhalación/análisis , Pulmón/efectos de los fármacos , Pulmón/patología , Metales Pesados/toxicidad , Estrés Oxidativo/efectos de los fármacos , Animales , Biomarcadores/sangre , Relación Dosis-Respuesta a Droga , Femenino , Sedimentos Geológicos/química , Pulmón/metabolismo , Metales Pesados/análisis , Ratones Endogámicos , Nevada , Tamaño de la Partícula , Neumonía/inducido químicamente , Neumonía/metabolismo , Neumonía/patología , Propiedades de SuperficieRESUMEN
The risk posed by prolonged exposure to space radiation represents a significant obstacle to long-duration human space exploration. Of the ion species present in the galactic cosmic ray spectrum, relativistic protons are the most abundant and as such are a relevant point of interest with regard to the radiation protection of space crews involved in future long-term missions to the Moon, Mars, and beyond. This work compared the shielding effectiveness of a number of standard and composite materials relevant to the design and development of future spacecraft or planetary surface habitats. Absorbed dose was measured using Al2O3:C optically stimulated luminescence dosimeters behind shielding targets of varying composition and depth using the 1 GeV nominal energy proton beam available at the NASA Space Radiation Laboratory at the Brookhaven National Laboratory in New York. Absorbed dose scored from computer simulations performed using the multi-purpose Monte Carlo radiation transport code FLUKA agrees well with measurements obtained via the shielding experiments. All shielding materials tested and modeled in this study were unable to reduce absorbed dose below that measured by the (unshielded) front detector, even after depths as large as 30 g/cm2. These results could be noteworthy given the broad range of proton energies present in the galactic cosmic ray spectrum, and the potential health and safety hazard such space radiation could represent to future human space exploration.
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Radiación Cósmica , Método de Montecarlo , Protones , Protección Radiológica , Vuelo Espacial , Protección Radiológica/instrumentación , Protección Radiológica/métodos , Humanos , Radiación Cósmica/efectos adversos , Dosis de Radiación , Nave Espacial , Simulación por ComputadorRESUMEN
Endoscopic ultrasound (EUS) has been established as a valuable diagnostic modality as it offers high-resolution imaging and fine-needle biopsy, which is essential in detecting and staging malignancies. Since the introduction of EUS-guided fine needle aspiration (EUS-FNA) in 1992, numerous novel EUS-based interventions and techniques have emerged. Currently, established interventional EUS techniques include celiac plexus block and neurolysis, drainage of pancreatic pseudocysts and pelvic fluid collections, and implantation of fiducial markers and radioactive seeds into the malignant tumors. Emerging EUS-guided experimental techniques include antitumor injection, ablation of tumors, and vascular access. Diagnostic and therapeutic access to the biliary tree and pancreatic duct is increasingly being used for failed ERCP procedures or inaccessible ducts. Interventional EUS is a very promising technique with many potential applications. The future holds promise for substantial progress in EUS-guided therapeutic interventions and their applications in clinical gastroenterology.
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Endosonografía/tendencias , Neoplasias/diagnóstico por imagen , Neoplasias/cirugía , Bloqueo Nervioso Autónomo/métodos , Biopsia con Aguja Fina/métodos , Ablación por Catéter/tendencias , Plexo Celíaco/diagnóstico por imagen , Plexo Celíaco/cirugía , Drenaje , Endosonografía/métodos , Marcadores Fiduciales/tendencias , Humanos , Inyecciones Intralesiones/tendencias , Radioisótopos de Yodo/administración & dosificación , Neoplasias/patología , Seudoquiste Pancreático/diagnóstico por imagen , Seudoquiste Pancreático/cirugía , Pelvis/diagnóstico por imagen , Pelvis/cirugía , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Resultado del Tratamiento , Ultrasonografía Intervencional/tendenciasRESUMEN
Contamination of drinking water by per- and polyfluoroalkyl substances (PFASs) emitted from manufacturing plants, fire-fighting foams, and urban waste streams has received considerable attention due to concerns over toxicity and environmental persistence; however, PFASs in ambient air remain poorly understood, especially in the United States (US). We measured PFAS concentrations in ambient fine particulate matter (PM2.5) at 5 locations across North Carolina over a 1 year period in 2019. Thirty-four PFASs, including perfluoroalkyl carboxylic, perfluoroalkane sulfonic, perfluoroalkyl ether carboxylic and sulfonic acids were analyzed by UHPLC/ESI-MS/MS. Quarterly averaged concentrations ranged from <0.004-14.1 pg m-3. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) ranged from <0.18 to 14.1 pg m-3, comparable to previous PM2.5 measurements from Canada and Europe (<0.02-3.5 pg m-3). Concentrations above 1 pg m-3 were observed in July-September at Charlotte (14.1 pg m-3, PFOA), Wilmington (4.75 pg m-3, PFOS), and Research Triangle Park (1.37 pg m-3, PFOS). Notably, PM2.5 has a short atmospheric lifetime (<2 weeks), and thus, the presence of PFOS in these samples raises questions about their sources, since PFOS production was phased out in the US â¼20 years ago. This is the first US study to provide insights into ambient PFAS concentrations in PM2.5.
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Ácidos Alcanesulfónicos , Fluorocarburos , Ácidos Alcanesulfónicos/análisis , Canadá , Europa (Continente) , Fluorocarburos/análisis , North Carolina , Material Particulado , Espectrometría de Masas en TándemRESUMEN
The role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with flow cytometry for the diagnosis of primary pancreatic lymphoma (PPL) has not been previously described. Our aims were to describe the EUS features of PPL and the role of EUS-FNA with and without flow cytometry in the diagnosis of 16 patients. When EUS-FNA with flow cytometry was compared with EUS-FNA without flow cytometry, the sensitivities for diagnosing non-Hodgkin's lymphoma were 84.6 % versus 30.8 %, respectively ( P = 0.01). EUS-FNA with flow cytometry is a valuable tool to diagnose PPL. Flow cytometry analysis complements traditional assessment by standard cytology.
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Endoscopía Gastrointestinal/métodos , Citometría de Flujo , Linfoma no Hodgkin/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Ultrasonografía Intervencional , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina , Femenino , Humanos , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Estudios RetrospectivosRESUMEN
BACKGROUND AND STUDY AIMS: ThinPrep is often used for endoscopic ultrasound fine-needle aspiration (EUS-FNA) samples but the sensitivity of this method is unknown. The objective of the study was to compare sensitivity and accuracy of ThinPrep versus the smear method in pancreas and lymph node samples obtained by EUS-FNA. PATIENTS AND METHODS: Patients with suspected malignancy in the pancreas or lymph node underwent EUS-FNA. On-site rapid assessment of all aspirates using the smear method was performed. After rapid assessment, three additional passes from each site were submitted into ThinPrep liquid medium. Cytopathologists interpreting the smear method and ThinPrep slides were blinded to each other. The gold standard was final cytology or pathology results. RESULTS: A total of 130 patients (36 % women, mean age 63 years) underwent EUS-FNA of 139 sites (50 pancreas, 89 lymph node). Malignancy was confirmed in 47 pancreas samples (94 %) and 48 lymph node samples (54 %). Mean +/- SD number of passes made for the smear method was 2.6 +/- 1.3. For pancreatic cancer, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the ThinPrep versus the smear method were: 62 % versus 98 %, 100 % versus 100 %, 100 % versus 100 %, 14 % versus 75 %, and 64 % versus 98 %, respectively. For lymph nodes the values were 67 % versus 92 %, 100 % versus 98 %, 100 % versus 98 %, 72 % versus 72 %, and 82 % versus 94 %, respectively. CONCLUSIONS: The smear method is more sensitive and accurate than ThinPrep in detecting malignancy from EUS-FNA samples of the pancreas and lymph nodes. Smear method with on-site rapid assessment should be favored over ThinPrep in suspected malignancy.
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Adenocarcinoma/secundario , Biopsia con Aguja Fina/métodos , Endosonografía/métodos , Técnicas de Preparación Histocitológica/métodos , Neoplasias Pancreáticas/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirugía , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pancreatectomía , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Estudios Prospectivos , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
The risk to space crew health and safety posed by exposure to space radiation is regarded as a significant obstacle to future human exploration missions to the Moon, Mars, and beyond. Engineers developing future spacecraft or planetary surface habitats can benefit from detailed knowledge of a broad range of possible materials that could provide improved protection to space crews from the deleterious effects of prolonged exposure to the space radiation environment. As one step towards providing this knowledge base, we have developed an empirical weighted figure of merit, referred to as shielding effectiveness, that quantifies the ability of a candidate material to shield space crews from the space radiation environment. The shielding effectiveness, as formulated in this study, accounts for the competing physical aspects of target and projectile fragmentation to provide a comprehensive assessment of radiation protection with regard to passive shielding for space applications. The empirical data used in determining shielding effectiveness was obtained from proton and heavy ion accelerator-based experiments wherein Al2O3:C optically stimulated luminescence dosimeter and CR-39 plastic nuclear track detector were irradiated behind candidate space radiation shielding materials of varying composition and depth. As a test case, the experimental setup was exposed to nominal beams of 1â¯GeV protons, and 1 GeV/n 28Si and 56Fe heavy ions, the latter serving as a sample of the high linear energy transfer portion of the galactic cosmic ray spectrum. Established radiation dosimetry techniques were used to obtain linear energy transfer spectra, absorbed dose, and dose equivalent as a function of depth. Based on the measurement results, a shielding effectiveness value was computed, quantifying the efficacy of the candidate material as a function of depth, with cumulative weighting factors accounting for the measured percent composition of baryonic matter in the galactic cosmic ray spectrum, and the measured percent contribution to absorbed dose and dose equivalent. The methodology for shielding effectiveness was tested using the common materials of aluminum, copper, graphite, and water, with polyethylene serving as the standard reference. The preliminary shielding effectiveness values for these materials confirm the low Z principle for effective space radiation shielding, and, furthermore, these values tend to be lower when the effectiveness calculation is based on dose equivalent. Of the common materials studied here, at a bulkhead depth of 5â¯g/cm2, all materials provide a similar level of radiation protection to within standard error. In addition, this method can be used to supplement and/or verify similar findings obtained from transport models.
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Radiación Cósmica , Protección Radiológica/métodos , Nave Espacial , Aluminio/química , Cobre/química , Grafito/química , Polietileno/química , Agua/químicaRESUMEN
Electroconvulsive shock or frontal cortex stimulation administered to rats at 5 but not at 180 minutes after an initial administration of morphine sulfate disrupted the development of one-trial tolerance to the analgesic effects of morphine sulfate. It is suggested that development of tolerance may be mediated by cellular mechanisms and memory processes similar to those thought to underlie conventional learning.
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Corteza Cerebral/fisiología , Tolerancia a Medicamentos , Electrochoque , Morfina , Analgesia , Animales , Núcleo Caudado/fisiología , Estimulación Eléctrica , Aprendizaje/fisiología , Masculino , Ratas , Factores de TiempoRESUMEN
Signaling between microglia and neurons is poorly characterized in the pathophysiology of Alzheimer's disease (AD), particularly with regards to gene and environmental (GxE) interactions early in life. This study investigated the maladaptation of microglia:neuron signaling and subsequent susceptibility to neurodegeneration using a developmental origin of adult disease (DOAD) model of AD, characterized previously. Here, we report that postnatal exposure to lead (Pb) in a transgenic (Tg) rodent model of AD resulted in significant female bias consequent to GxE interactions. Atypical, non-neuroprotective microglial phenotypes were observed months after cessation of Pb exposure, as well as evidence for neuronal compensation, that was not observed in WT mice. Specifically, microglia from Pb-exposed Tg (GxE) females exhibited atypical polarization profiles for activation earlier and more severely than males and WT mice, that persisted over time to become contextually maladaptive. By postnatal day (PND) 240, microglia from GxE females also sequestered less neurotoxic iron in the hippocampus. In the same GxE female population, measures of neuronal parameters, such as hippocampal TrkB expression, revealed evidence of disharmonious and compensatory interactions with microglia within the pathological progression. Likewise, GxE interactions resulted in female-biased, late-life changes to key synaptic proteins crucial to synapse dynamics and microglial signaling. These incongruent microglia:neuronal dynamics were observed in GxE males at later ages compared to females, and not observed in either gene- or environment-only populations. Altogether, our results support a gene x environment model of female-biased microglial susceptibility to later-life development of AD, and highlight markers for maladaptive microglia:neuron signaling and compensation.
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Enfermedad de Alzheimer/fisiopatología , Hipocampo/patología , Microglía/patología , Neuronas/fisiología , Factores Sexuales , Enfermedad de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Animales , Modelos Animales de Enfermedad , Sinapsis Eléctricas , Femenino , Regulación del Desarrollo de la Expresión Génica , Interacción Gen-Ambiente , Hipocampo/metabolismo , Humanos , Masculino , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Compuestos Organometálicos/toxicidad , Presenilina-1/genética , Proteínas Tirosina Quinasas/metabolismo , Transducción de Señal , Proteínas tau/genéticaRESUMEN
BACKGROUND: Despite intensive efforts to engage people living with HIV in the United States, less than half of the youth aged 13 to 24 years achieve viral suppression. There is a clear and continued need for innovative behavioral programs that support optimizing adherence among young persons with HIV. OBJECTIVE: There are 3 phases of this project. Phase 1 involves conducting focus groups to obtain feedback from youth about an existing technology-based antiretroviral therapy (ART) adherence intervention. Phase 2 will be used to conduct beta testing with youth to refine and finalize the YouTHrive (YT) intervention. Phase 3 is a randomized controlled trial (RCT) to test the efficacy of the YT intervention among youth living with HIV (YLWH). METHODS: In phase 1, we will conduct 6 focus groups with approximately 8 youths (aged 15-19 years) and young adults (aged 20-24 years), each in 3 US cities to obtain (1) feedback from YLWH about the look and feel and content of an existing adult-focused Web-based ART adherence intervention and (2) suggestions for adapting the intervention for YLWH similar to themselves. Phase 2 will involve updating the existing intervention to include features and functionality recommended by YLWH in phase 1; it will conclude with beta testing with 12 participants to gain feedback on the overall design and ensure proper functionality and ease of navigation. For phase 3, we will enroll 300 YLWH in 6 US cities (Atlanta, Chicago, Houston, New York City, Philadelphia, and Tampa) into a 2-arm prospective RCT. Participants will be randomized 1:1 to YT intervention or control group. The randomization sequence will be stratified by city and use random permuted blocks of sizes 2 and 4. Participants randomized to the control condition will view a weekly email newsletter on topics related to HIV, with the exception of ART adherence, for 5 months. Participants randomized to the YT intervention condition will be given access to the YT site for 5 months. Study assessments will occur at enrollment and 5, 8, and 11 months post enrollment. The primary outcome that will be assessed is sustained viral load (VL), defined as the proportion of participants in each study arm who have suppressed VL at both the 5- and 11-month assessment; the secondary outcome that will be assessed is suppressed VL at both the 5- and 11-month assessment between drug-using and nondrug-using participants assigned to the YT intervention arm. RESULTS: Participant recruitment began in May 2017 for phase 1 of the study. The data collection for aim 3 is anticipated to end in April 2020. CONCLUSIONS: The efficacy trial of the YT intervention will help to fill gaps in understanding the efficacy of mobile interventions to improve ART adherence among at-risk populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03149757; https://clinicaltrials.gov/ct2/show/NCT03149757 (Archived by WebCite at http://www.webcitation.org/73pw57Cf1). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11502.
RESUMEN
Pancreatic neuroendocrine tumors (PNETs) may rarely appear as cystic or mixed solid-cystic masses. The endoscopic ultrasound (EUS) morphology and cyst fluid characteristics of these tumors are not well clarified. We retrospectively identified nine adult patients with nine single cystic pancreatic neuroendocrine tumors (CNETs). These nine included 0.67 % of the 1344 patients with pancreatic cystic lesions and 9.5 % of the 95 confirmed PNETs evaluated over the 12-year study period. At presentation, four patients were asymptomatic and five had known acute pancreatitis (n = 2), MEN-1 syndrome with hypoglycemia (n = 1), and abdominal pain (n = 2). Median maximal tumor diameter was 26 mm (range 20 - 64 mm). EUS morphology was mixed solid and cystic (n = 4) or cystic alone (n = 5). Cytology from EUS-fine-needle aspiration (FNA) (median 2 passes; range 1 - 6) demonstrated a PNET, and immunocytochemistry was confirmatory in all patients. Cyst fluid carcinoembryonic antigen (CEA) (n = 4) and amylase (n = 5) ranged from 0.1 to 1.8 ng/ml (normal 0 - 2.5 ng/ml) and 72 to 1838 U/L (normal 25 - 161 U/L), respectively. Six patients underwent surgery, and the preoperative diagnosis was confirmed in all.
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Endosonografía , Neoplasias Pancreáticas/diagnóstico por imagen , Biopsia con Aguja , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico por imagen , Neoplasia Endocrina Múltiple Tipo 1/patología , Quiste Pancreático/diagnóstico por imagen , Quiste Pancreático/patología , Neoplasias Pancreáticas/patología , Estudios RetrospectivosRESUMEN
BACKGROUND AND STUDY AIMS: Solid pseudopapillary tumors of the pancreas are rare, low-grade, epithelial neoplasms that are usually discovered incidentally in young women. Distinguishing solid pseudopapillary tumors from other pancreatic tumors, especially pancreatic endocrine tumors, can be challenging. The role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in this context remains unclear. The purpose of this study was to describe the endoscopic ultrasound features of solid pseudopapillary tumors and the role of EUS-FNA in the preoperative diagnosis of these tumors. PATIENTS AND METHODS: Patients from five tertiary referral centers with surgically confirmed solid pseudopapillary tumors who had undergone preoperative EUS-FNA were included. The endoscopic ultrasound findings, cytologic descriptions, immunostaining results, operative records, surgical pathology, and results of the most recent clinical follow-up were reviewed. RESULTS: A total of 28 patients were identified (four men [14 %], 24 women [86 %], mean age +/- standard deviation [SD] 35 +/- 10 years). Solid pseudopapillary tumors had been found as incidental findings on cross-sectional imaging in 50 % of cases. The mean tumor size +/- SD was 42 +/- 19.5 mm and the majority were located in the pancreatic body and tail. The endoscopic ultrasound report described a well-defined, echo-poor mass in 86 %; the tumors were solid in 14 patients (50 %), mixed solid and cystic in 11 patients (39 %), and cystic in three patients (11 %). A preoperative diagnosis of solid pseudopapillary tumor was made in 21 patients (75 %) on the basis of EUS-FNA cytology. Surgical resection was performed in all cases. Laparoscopic resection was performed in eight of these patients (29 %). CONCLUSIONS: A solid pseudopapillary tumor should be included in the differential diagnosis of any well-demarcated, echo-poor, solid or mixed solid/cystic pancreatic lesion seen during endoscopic ultrasound, particularly in young women. The diagnostic accuracy of EUS-FNA for solid pseudopapillary tumors was 75 % in this study. A definitive preoperative diagnosis can guide the surgical approach in selected cases.
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Biopsia con Aguja Fina/métodos , Endosonografía , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Adolescente , Adulto , Estudios de Cohortes , Femenino , Humanos , Hallazgos Incidentales , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/cirugía , Estudios Retrospectivos , Cirugía Asistida por ComputadorRESUMEN
As the resident macrophage of the central nervous system, microglia are thought to contribute to Alzheimer's disease (AD) pathology through lack of neuroprotection. The role of immune dysfunction in AD may be due to disruption of regulatory signals for the activation of microglia that may occur early in development. We hypothesized that early toxicant exposure would systematically activate microglia, possibly reversing the pathological severity of AD. Offspring of a triple transgenic murine model for AD (3×TgAD) were exposed to a model neurotoxicant, lead acetate, from postnatal days (PND) 5-10. Our results indicated that female mice exposed to Pb had a greater and earlier incidence of amyloid burden within the hippocampus, coinciding with decreased markers of microglial activation at PND 50. Pb-exposed males had increased microglial activation at PND 50, as evidence by CD11b expression and microglial abundance, with no significant increase in amyloid burden at that time. There was greater amyloid burden at PND 90 and 180 in both male and female mice exposed to Pb compared with control. Together, these data suggest that activated microglia are neuroprotective against amyloid accumulation early in AD pathology, and that early exposure to Pb could increase susceptibility to later-life neurodegeneration. Likewise, females may be more susceptible to early-life microglial damage, and, subsequently, AD. Further investigation into the sex biased mechanisms by which microglial activation is altered by an early-life immune insult will provide critical insight into the temporal susceptibility of the developing neuroimmune system and its potential role in AD etiopathology.
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Enfermedad de Alzheimer/metabolismo , Modelos Animales de Enfermedad , Plomo/toxicidad , Microglía/metabolismo , Placa Amiloide/metabolismo , Caracteres Sexuales , Factores de Edad , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/patología , Animales , Femenino , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Transgénicos , Microglía/efectos de los fármacos , Microglía/patología , Placa Amiloide/inducido químicamente , Placa Amiloide/patología , EmbarazoRESUMEN
BACKGROUND: Patients with intraductal papillary mucinous neoplasm (IPMN) are at risk for invasive pancreatic cancer. We aim to characterize the impact of smoking on IPMN malignant progression. METHODS: Patients undergoing pancreatic resection for IPMN (1991-2015) were retrospectively reviewed using a prospectively collected database. RESULTS: Of 422 patients identified, 324 had complete data for analysis; 55% were smokers. Smoking status did not impact IPMN malignant progression (smokers/non-smokers: 22%/18% invasive grade; p = 0.5). Smokers were younger than non-smokers at the time of IPMN diagnosis (63 versus 68 years; p = 0.001). This association also held in the invasive IPMN subgroup (65 versus 72 years, p = 0.01). Despite this observation, rate of symptoms at diagnosis, cancer stage, and median survival were the same between smokers and non-smokers. CONCLUSION: Although smoking is not associated with IPMN malignant progression, invasive IPMN is diagnosed at a younger age in smokers. These data suggest tobacco exposure may accelerate IPMN malignant progression.
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Adenocarcinoma Mucinoso/patología , Carcinoma Ductal Pancreático/patología , Progresión de la Enfermedad , Neoplasias Pancreáticas/patología , Fumar , Adenocarcinoma Mucinoso/cirugía , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/cirugía , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/cirugía , Estudios RetrospectivosRESUMEN
Necroptosis is a caspase-independent form of regulated cell death executed by the receptor-interacting protein kinase 1 (RIP1), RIP3, and mixed lineage kinase domain-like protein (MLKL). Recently, necroptosis-based cancer therapy has been proposed to be a novel strategy for antitumor treatment. However, a big controversy exists on whether this type of therapy is feasible or just a conceptual model. Proponents believe that because necroptosis and apoptosis use distinct molecular pathways, triggering necroptosis could be an alternative way to eradicate apoptosis-resistant cancer cells. This hypothesis has been preliminarily validated by recent studies. However, some skeptics doubt this strategy because of the intrinsic or acquired defects of necroptotic machinery observed in many cancer cells. Moreover, two other concerns are whether or not necroptosis inducers are selective in killing cancer cells without disturbing the normal cells and whether it will lead to inflammatory diseases. In this review, we summarize current studies surrounding this controversy on necroptosis-based antitumor research and discuss the advantages, potential issues, and countermeasures of this novel therapy.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Humanos , NecrosisRESUMEN
This American Society for Gastrointestinal Endoscopy guideline provides evidence-based recommendations for the endoscopic management of gastric outlet obstruction (GOO). We applied the Grading of Recommendations, Assessment, Development and Evaluation methodology to address key clinical questions. These include the comparison of (1) surgical gastrojejunostomy to the placement of self-expandable metallic stents (SEMS) for malignant GOO, (2) covered versus uncovered SEMS for malignant GOO, and (3) endoscopic and surgical interventions for the management of benign GOO. Recommendations provided in this document were founded on the certainty of the evidence, balance of benefits and harms, considerations of patient and caregiver preferences, resource utilization, and cost-effectiveness.