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Integrating precision diagnostics into personalized treatments requires understanding how biomarkers relate to clinical outcomes. Various clinical data collection methods exist, each with strengths and weaknesses. Interventional data are high quality but narrowly focused. Real-world data (RWD) provide broader information but with variable quality. Master protocols allow better efficiency in data collection. The master observational trial bridges the gap between interventional and retrospective RWD collection methods. To view this SnapShot, open or download the PDF.
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Ensayos Clínicos como Asunto , Recolección de Datos , Medicina de Precisión , HumanosRESUMEN
This commentary introduces a new clinical trial construct, the Master Observational Trial (MOT), which hybridizes the power of molecularly based master interventional protocols with the breadth of real-world data. The MOT provides a clinical venue to allow molecular medicine to rapidly advance, answers questions that traditional interventional trials generally do not address, and seamlessly integrates with interventional trials in both diagnostic and therapeutic arenas. The result is a more comprehensive data collection ecosystem in precision medicine.
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Estudios Observacionales como Asunto/métodos , Medicina de Precisión/métodos , Proyectos de Investigación/normas , Macrodatos , Protocolos de Ensayos Clínicos como Asunto , Humanos , Terapia Molecular Dirigida/métodos , Terapia Molecular Dirigida/tendencias , Estudios Observacionales como Asunto/normasRESUMEN
Identifying modifiers of dosage-sensitive genes involved in neurodegenerative disorders is imperative to discover novel genetic risk factors and potential therapeutic entry points. In this study, we focus on Ataxin-1 (ATXN1), a dosage-sensitive gene involved in the neurodegenerative disease spinocerebellar ataxia type 1 (SCA1). While the precise maintenance of ATXN1 levels is essential to prevent disease, the mechanisms that regulate ATXN1 expression remain largely unknown. We demonstrate that ATXN1's unusually long 5' untranslated region (5' UTR) negatively regulates its expression via posttranscriptional mechanisms. Based on recent reports that microRNAs (miRNAs) can interact with both 3' and 5' UTRs to regulate their target genes, we identify miR760 as a negative regulator that binds to a conserved site in ATXN1's 5' UTR to induce RNA degradation and translational inhibition. We found that delivery of Adeno-associated virus (AAV)-expressing miR760 in the cerebellum reduces ATXN1 levels in vivo and mitigates motor coordination deficits in a mouse model of SCA1. These findings provide new insights into the regulation of ATXN1 levels, present additional evidence for miRNA-mediated gene regulation via 5' UTR binding, and raise the possibility that noncoding mutations in the ATXN1 locus may act as risk factors for yet to be discovered progressive ataxias.
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Regiones no Traducidas 5'/genética , Ataxina-1/genética , Regulación de la Expresión Génica/genética , MicroARNs/metabolismo , Ataxias Espinocerebelosas/genética , Animales , Ataxina-1/metabolismo , Línea Celular , Humanos , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Mutación , Factores de Riesgo , Ataxias Espinocerebelosas/fisiopatologíaRESUMEN
BACKGROUND: There is sparse literature on the effect of preoperative immunotherapy on complications after surgery for primary head and neck squamous cell carcinoma (HNSCC). The objectives are to compare complication rates in patients receiving surgery with and without neoadjuvant immune checkpoint inhibitors (nICI) for primary HNSCC and to evaluate factors associated with increased odds of surgical complications. METHODS: A retrospective review of patients who underwent ablation and free flap reconstruction or transoral robotic surgery (TORS) for primary HNSCC between 2017-2021 was conducted. Complications were compared between patients who underwent surgery with or without nICI before and after propensity score matching. Regression analysis to estimate odds ratios was performed. RESULTS: A total of 463 patients met inclusion criteria. Free flap reconstruction constituted 28.9% of patients and TORS constituted 71.1% of patients. nICI was administered in 83 of 463 (17.9%) patients. There was no statistically significant difference in surgical, medical, or overall complications between patients receiving surgery with or without nICI. In the unmatched cohort, multivariable model identified non-White race, former/current smoking history, free flap surgery, and perineural invasion as factors significantly associated with increased complications. In the matched cohort, multivariable model identified advanced age and free flap surgery as factors significantly associated with increased complications. PLAIN LANGUAGE SUMMARY: It is safe to give immunotherapy before major surgery in patients who have head and neck cancer. Advanced age, non-White race, current/former smoking, free flap surgery, and perineural invasion may be associated with increased the odds of surgical complications.
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Neoplasias de Cabeza y Cuello , Procedimientos de Cirugía Plástica , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Ligandos , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/cirugía , Estudios RetrospectivosRESUMEN
STUDY OBJECTIVE: Temperature control trials in cardiac arrest patients have not reliably conferred neuroprotective benefit but have been limited by inconsistent treatment parameters. To evaluate the presence of a time dependent treatment effect, we assessed the association between preinduction time and clinical outcomes. METHODS: In this retrospective, single academic center study between 2014 and 2022, consecutive out-of-hospital cardiac arrest (OHCA) patients treated with temperature control were identified. Preinduction was defined as the time from hospital arrival to initiation of a closed-loop temperature feedback device [door to temperature control initiation time], and early door to temperature control device time was defined a priori as <3 hours. We assessed the association between good neurologic outcome (cerebral performance category 1 to 2) and door to temperature control device time using logistic regression. The proportion of patients who survived to hospital discharge was evaluated as a secondary outcome. A sensitivity analysis using inverse probability treatment weighting, created using a propensity score, was performed to minimize measurable confounding. RESULTS: Three hundred and forty-seven OHCA patients were included; the early door to temperature control device cohort included 75 (21.6%) patients with a median (interquartile range) door to temperature control device time of 2.50 (2.03 to 2.75) hours, whereas the late door to temperature control device cohort included 272 (78.4%) patients with a median (interquartile range) door to temperature control device time of 5.18 (4.19 to 6.41) hours. In the multivariable logistic regression model, early door to temperature control device time was associated with improved good neurologic outcome and survival before [adjusted odds ratio (OR) (95% confidence interval) 2.36 (1.16 to 4.81) and 3.02 (1.54 to 6.02)] and after [adjusted OR (95% confidence interval) 1.95 (1.19 to 3.79) and 2.14 (1.33 to 3.36)] inverse probability of treatment weighting, respectively. CONCLUSION: In our study of OHCA patients, a shorter preinduction time for temperature control was associated with improved good neurologic outcome and survival. This finding may indicate that early initiation in the emergency department will confer benefit. Our findings are hypothesis generating and need to be validated in future prospective trials.
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The first record of captive-bred red foxes (Vulpes vulpes) dates to 1896 when a breeding enterprise emerged in the provinces of Atlantic Canada. Because its domestication happened during recent history, the red fox offers a unique opportunity to examine the genetic diversity of an emerging domesticated species in the context of documented historical and economic influences. In particular, the historical record suggests that North American and Eurasian farm-bred populations likely experienced different demographic trajectories. Here, we focus on the likely impacts of founder effects and genetic drift given historical trends in fox farming on North American and Eurasian farms. A total of 15 mitochondrial haplotypes were identified in 369 foxes from 10 farm populations that we genotyped (nâ =â 161) or that were previously published. All haplotypes are endemic to North America. Although most haplotypes were consistent with eastern Canadian ancestry, a small number of foxes carried haplotypes typically found in Alaska and other regions of western North America. The presence of these haplotypes supports historical reports of wild foxes outside of Atlantic Canada being introduced into the breeding stock. These putative Alaskan and Western haplotypes were more frequently identified in Eurasian farms compared to North American farms, consistent with historical documentation suggesting that Eurasian economic and breeding practices were likely to maintain low-frequency haplotypes more effectively than in North America. Contextualizing inter- vs. intra-farm genetic diversity alongside the historical record is critical to understanding the origins of this emerging domesticate and the relationships between wild and farm-bred fox populations.
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Zorros , Variación Genética , Haplotipos , Zorros/genética , Animales , ADN Mitocondrial/genética , Canadá , Genética de Población , Animales Domésticos/genética , Domesticación , Cruzamiento , Efecto Fundador , Flujo Genético , GranjasRESUMEN
BACKGROUND: Globally, individuals with mental illness get in contact with the law at a greater rate than the general population. The goal of this review was to identify and describe: (1) effectiveness of mental health interventions for individuals with serious mental illness (SMI) who have criminal legal involvement; (2) additional outcomes targeted by these interventions; (3) settings/contexts where interventions were delivered; and (4) barriers and facilitating factors for implementing these interventions. METHODS: A systematic review was conducted to summarize the mental health treatment literature for individuals with serious mental illness with criminal legal involvement (i.e., bipolar disorder, schizophrenia, major depressive disorder). Searches were conducted using PsychINFO, Embase, ProQuest, PubMed, and Web of Science. Articles were eligible if they were intervention studies among criminal legal involved populations with a mental health primary outcome and provided description of the intervention. RESULTS: A total of 13 eligible studies were identified. Tested interventions were categorized as cognitive/behavioral, community-based, interpersonal (IPT), psychoeducational, or court-based. Studies that used IPT-based interventions reported clinically significant improvements in mental health symptoms and were also feasible and acceptable. Other interventions demonstrated positive trends favoring the mental health outcomes but did not show statistically and clinically significant changes. All studies reported treatment outcomes, with only 8 studies reporting both treatment and implementation outcomes. CONCLUSION: Our findings highlight a need for more mental health research in this population. Studies with randomized design, larger sample size and studies that utilize non-clinicians are needed.
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Derecho Penal , Trastornos Mentales , Humanos , Trastornos Mentales/terapia , Trastornos Mentales/psicología , Criminales/psicologíaRESUMEN
BACKGROUND: The standard of care for congestive heart failure (CHF) aims to slow disease progression and maximize patient function, however there is an increase in emergency department (ED) revisits and readmissions. Social risk factors play a role in the disease management and prognosis of CHF. There is a gap in the identification of low-risk CHF patient who would be safely discharged using an initial social risk factor stratification. OBJECTIVES: To generate a social risk profile for patients presenting to the ED with acute CHF exacerbation and identify variables that may increase the risk of 7-day and overall mortality, 30-day ED revisit, and readmission. METHODS: We conducted a pilot prospective survey-based study among adult patients presenting to the ED with acute CHF exacerbation. The combination of a self-report questionnaire and retrospective chart review was used to generate a CHF risk profile. RESULTS: A total of 62 patients were recruited in the pilot study with a mean age of 69.5 years. The preliminary data indicated that prior to this ED visit, 21% of patients were not aware of a previous CHF diagnosis; 64.5% of patients rated their sleep quality as poor or very poor; 72.6% reported orthopnea; and 43.5% reported recent weight gain. 37.1% of patients did not adhere to dietary recommendations and some patients did not adhere to their medication regime 100%. CONCLUSION: This study suggests establishing a social risk profile for patients presenting to the ED with CHF can help formulate a CHF-specific care plan and optimize multidisciplinary management to reduce ED revisits and readmissions.
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OBJECTIVE: Oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), which is the ratio of VO2 to VCO2, are critical indicators of human metabolism. To seek a link between the patient's metabolism and pathophysiology of critical illness, we investigated the correlation of these values with mortality in critical care patients. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older healthy volunteers and patients who underwent mechanical ventilation were enrolled. A high-fidelity automation device, which accuracy is equivalent to the gold standard Douglas Bag technique, was used to measure VO2, VCO2, and RQ at a wide range of fraction of inspired oxygen (FIO2). RESULTS: We included a total of 21 subjects including 8 post-cardiothoracic surgery patients, 7 intensive care patients, 3 patients from the emergency room, and 3 healthy volunteers. This study included 10 critical care patients, whose metabolic measurements were performed in the ER and ICU, and 6 died. VO2, VCO2, and RQ of survivors were 282 +/- 95 mL/min, 202 +/- 81 mL/min, and 0.70 +/- 0.10, and those of non-survivors were 240 +/- 87 mL/min, 140 +/- 66 mL/min, and 0.57 +/- 0.08 (p = 0.34, p = 0.10, and p < 0.01), respectively. The difference of RQ was statistically significant (p < 0.01) and it remained significant when the subjects with FIO2 < 0.5 were excluded (p < 0.05). CONCLUSIONS: Low RQ correlated with high mortality, which may potentially indicate a decompensation of the oxygen metabolism in critically ill patients.
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Pulmón , Respiración Artificial , Humanos , Adolescente , Estudios Prospectivos , Calorimetría Indirecta/métodos , Consumo de Oxígeno , Dióxido de Carbono/metabolismo , Enfermedad Crítica/terapia , OxígenoRESUMEN
Pulmonary balloon valvuloplasty (PBV) is the treatment of choice for subjects with isolated pulmonary valve stenosis (IPS). The purpose of this study was to define fetal echocardiographic features associated with an inpatient PBV prior to newborn hospital discharge and characterize resource utilization of IPS fetuses among participating centers. Six center, retrospective case series of singleton fetuses identified between 2010 and 2020 with IPS. Third-trimester echocardiogram data was compared with postnatal data, included pulmonary valve Doppler velocities, pulmonary valve insufficiency and ductus arteriosus flow direction. Comparison between subjects who underwent inpatient PBV during their newborn hospital admission versus those infants referred for outpatient PBV after initial hospital discharge. We analyzed data by logistic regression, student t test and Chi-Square testing with a p value of ≤ 0.05 considered statistically significant. Forty-nine IPS fetuses were identified. Thirty-eight (78%) underwent inpatient PBV at 5 (range 1-58) days and 11 (22%) underwent outpatient PBV at 51.8 (11-174) days. Newborns requiring an inpatient PBV were more likely to have one or more characteristics on 3rd-trimester fetal echocardiogram: left to right or bidirectional ductus arteriosus flow (61% vs 0%), and/or a peak pulmonary valve velocity > 3.0 m/s (odds ratio 16.9, 95% confidence interval 3.02-94.17) with a sensitivity of 90.4% and specificity of 97.7%. Ductus arteriosus flow direction and pulmonary valve peak velocity in the 3rd trimester can successfully predict the need for newborn inpatient PBV. We speculate these findings may be useful in choosing delivery site for the pregnancy complicated by fetal IPS.
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Valvuloplastia con Balón , Conducto Arterioso Permeable , Conducto Arterial , Estenosis de la Válvula Pulmonar , Lactante , Femenino , Embarazo , Humanos , Recién Nacido , Estudios Retrospectivos , Ecocardiografía , Tercer Trimestre del Embarazo , Estenosis de la Válvula Pulmonar/diagnóstico por imagen , Estenosis de la Válvula Pulmonar/cirugía , Ultrasonografía PrenatalRESUMEN
The Cold Pool is a subsurface layer with water temperatures below 2 °C that is formed in the eastern Bering Sea. This oceanographic feature of relatively cooler bottom temperature impacts zooplankton and forage fish dynamics, driving different energetic pathways dependent upon Bering Sea climatic regime. Odontocetes echolocate to find prey, so tracking foraging vocalizations acoustically provides information to understand the implications of climate change on Cold Pool variability influencing regional food web processes. Vocal foraging dynamics of ice-associated and seasonally migrant marine mammal species suggest that sperm whales spend more time searching for prey in warm years when the Cold Pool is reduced but are more successful at capturing prey during cold years when the Cold Pool is stronger. Beluga whale foraging vocal activity was relatively consistent across climate regimes but peaked during the warm regime. Killer whale foraging vocal activity peaked in both warm and cold regimes with indicators of different ecotypes exploiting changing prey conditions across climate regimes. Foraging activity of odontocete apex predators may serve as a sentinel indicator of future ecosystem change related to prey availability that is linked to a diminishing Cold Pool as water temperatures rise and seasonal sea ice decreases due to climate change.
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Ballena Beluga , Orca , Animales , Ecosistema , Temperatura , Cachalote , AguaRESUMEN
Therapy using anti-PD-1 immune checkpoint inhibitors (ICI) has revolutionized the treatment of many cancers including head and neck squamous cell carcinomas (HNSCC), but only a fraction of patients respond. To better understand the molecular mechanisms driving resistance, we performed extensive analysis of plasma and tumor tissues before and after a 4-week neoadjuvant trial in which HNSCC patients were treated with the anti-PD-1 inhibitor, nivolumab. Luminex cytokine analysis of patient plasma demonstrated that HPVpos nonresponders displayed high levels of the proinflammatory chemokine, interleukin-8 (IL-8), which decreased after ICI treatment, but remained higher than responders. miRNAseq analysis of tetraspanin-enriched small extracellular vesicles (sEV) purified from plasma of HPVpos nonresponders demonstrated significantly lower levels of seven miRNAs that target IL-8 including miR-146a. Levels of the pro-survival oncoprotein Dsg2, which has been to down-regulate miR-146a, are elevated with HPVpos tumors displaying higher levels than HPVneg tumors. Dsg2 levels decrease significantly following ICI in responders but not in nonresponders. In cultured HPVpos cells, restoration of miR-146a by forced expression or treatment with miR-146a-loaded sEV, reduced IL-8 level, blocked cell cycle progression, and promoted cell death. These findings identify Dsg2, miR-146a, and IL-8 as potential biomarkers for ICI response and suggest that the Dsg2/miR-146a/IL-8 signaling axis negatively impacts ICI treatment outcomes and could be targeted to improve ICI responsiveness in HPVpos HNSCC patients.
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Vesículas Extracelulares , Neoplasias de Cabeza y Cuello , MicroARNs , Infecciones por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Interleucina-8/genética , Nivolumab/farmacología , Nivolumab/uso terapéutico , Terapia Neoadyuvante , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Vesículas Extracelulares/metabolismoRESUMEN
BACKGROUND: Food insecurity is "the state of being without reliable access to a sufficient quantity of affordable, nutritious food". Observational studies have associated food insecurity with many negative health effects including the development and exacerbations of chronic diseases, higher health care use and increased mortality. Health care providers prescribing food is a growing area of interest and research, however it is not known how patients feel about receiving fruit and vegetable prescriptions (FVRx) from their health provider versus other means of food provision. This pilot study was conducted to explore the experiences and opinions of Canadian adults with food insecurity who were recipients of a FVRx box program prescribed by their health provider. METHODS: Potential participants were recruited to 3 focus groups using flyers included in their monthly food box. Questions were kept open to encourage participation of all group members. The focus groups were audiotaped, transcribed verbatim, and analyzed by the research team using descriptive qualitative research methodology. RESULTS: Participants described shame and frustration trying to obtain enough food through local food banks. In comparison, they perceived their team dietitian, family physician or addictions physician as directly helping them with their health by prescribing food. The boxed fruit and vegetables were prepared in many ways and often shared to reduce waste and to reduce the food insecurity of extended family members. Positive effects of the FVRx on physical and mental health were reported. Participants believed that follow up with their health provider helped support them and their behavioural changes towards better nutrition. Limitations of the program included lack of choice, non-flexible pick-up times and the program being limited to 6 months. Being able to choose their own fruit and vegetables, instead of receiving a set box, was suggested by most to help meal planning and to increase autonomy. CONCLUSIONS: Health providers prescribing FVRx boxes to adult patients with food insecurity was positively received in this study. Evaluation of similar programs in other regions in Canada and internationally, and comparison of food prescriptions to basic income guarantee programs is recommended.
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Frutas , Verduras , Adulto , Humanos , Proyectos Piloto , Abastecimiento de Alimentos , CanadáRESUMEN
OBJECTIVE: Using a system, which accuracy is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), we aimed to continuously measure these metabolic indicators and compare the values between post-cardiothoracic surgery and critical care patients. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older patients who underwent mechanical ventilation were enrolled. RESULTS: We included 4 post-surgery and 6 critical care patients. Of those, 3 critical care patients died. The longest measurement reached to 12 h and 15 min and 50 cycles of repeat measurements were performed. VO2 of the post-surgery patients were 234 ± 14, 262 ± 27, 212 ± 16, and 192 ± 20 mL/min, and those of critical care patients were 122 ± 20, 189 ± 9, 191 ± 7, 191 ± 24, 212 ± 12, and 135 ± 21 mL/min, respectively. The value of VO2 was more variable in the post-surgery patients and the range of each patient was 44, 126, 71, and 67, respectively. SOFA scores were higher in non-survivors and there were negative correlations of RQ with SOFA. CONCLUSIONS: We developed an accurate system that enables continuous and repeat measurements of VO2, VCO2, and RQ. Critical care patients may have less activity in metabolism represented by less variable values of VO2 and VCO2 over time as compared to those of post-cardiothoracic surgery patients. Additionally, an alteration of these values may mean a systemic distinction of the metabolism of critically ill patients.
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Cuidados Críticos , Consumo de Oxígeno , Humanos , Adolescente , Estudios Prospectivos , Calorimetría Indirecta/métodos , Respiración Artificial , Dióxido de Carbono/metabolismoRESUMEN
BACKGROUND: Recent jail detention is a marker for trait and state suicide risk in community-based populations. However, healthcare providers are typically unaware that their client was in jail and few post-release suicide prevention efforts exist. This protocol paper describes an effectiveness-implementation trial evaluating community suicide prevention practices triggered by advances in informatics that alert CareSource, a large managed care organization (MCO), when a subscriber is released from jail. METHODS: This randomized controlled trial investigates two evidence-based suicide prevention practices triggered by CareSource's jail detention/release notifications, in a partial factorial design. The first phase randomizes ~ 43,000 CareSource subscribers who pass through any Ohio jail to receive Caring Contact letters sent by CareSource or to Usual Care after jail release. The second phase (running simultaneously) involves a subset of ~ 6,000 of the 43,000 subscribers passing through jail who have been seen in one of 12 contracted behavioral health agencies in the 6 months prior to incarceration in a stepped-wedge design. Agencies will receive: (a) notifications of the client's jail detention/release, (b) instructions for re-engaging these clients, and (c) training in suicide risk assessment and the Safety Planning Intervention for use at re-engagement. We will track suicide-related and service linkage outcomes 6 months following jail release using claims data. CONCLUSIONS: This design allows us to rigorously test two intervention main effects and their interaction. It also provides valuable information on the effects of system-level change and the scalability of interventions using big data from a MCO to flag jail release and suicide risk. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT05579600). Registered 27 June, 2023.
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Cárceles Locales , Suicidio , Humanos , Programas Controlados de Atención en Salud , Ohio , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Ebstein anomaly is the most common form of tricuspid valve congenital anomalies. The tricuspid valve is abnormal with different degrees of displacement of the septal leaflet and abnormal rotation of the valve towards the right ventricular outflow tract. In severe forms, it results in significant tricuspid regurgitation and requires surgical repair. There is an increased interest in understanding the anatomy of the tricuspid valve in this lesion as the surgical repair has evolved with the invention and wide adoption of the cone operation. Multimodality imaging plays an important role in diagnosis, follow-up, surgical planning and post-operative care. This review provides anatomical tips for the cardiac imagers caring for patients with Ebstein anomaly and will help provide image-based personalized medicine.
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Procedimientos Quirúrgicos Cardíacos , Anomalía de Ebstein , Insuficiencia de la Válvula Tricúspide , Humanos , Anomalía de Ebstein/diagnóstico por imagen , Anomalía de Ebstein/cirugía , Resultado del Tratamiento , Válvula Tricúspide/diagnóstico por imagen , Procedimientos Quirúrgicos Cardíacos/métodosRESUMEN
Background: Hippocampal and cerebellar neuropathology occurs in individuals with alcohol use disorders (AUD), resulting in impaired cognitive and motor function.Objectives: Evaluate the effects of ethanol on the expression of pro- and anti-inflammatory molecules, as well as the effects of the anti-inflammatory PPAR-γ agonist pioglitazone in suppressing ethanol-induced neuroinflammation.Methods: Adult male and female mice were treated chronically with ethanol for just under a month followed by a single acute binge dose of ethanol. Animals were provided liquid diet in the absence of ethanol (Control; n = 18, 9 M/9F), liquid diet containing ethanol (ethanol; n = 22, 11 M/11F), or liquid diet containing ethanol plus gavage administration of 30.0 mg/kg pioglitazone (ethanol + pioglitazone; n = 20, 10 M/10F). The hippocampus and cerebellum were isolated 24 h following the binge dose of ethanol, mRNA was isolated, and pro- and anti-inflammatory molecules were quantified by qRT-PCR.Results: Ethanol significantly (p < .05) increased the expression of pro-inflammatory molecules IL-1ß, TNF-α, CCL2, and COX2; increased the expression of inflammasome-related molecules NLRP3 and Casp1 but decreased IL-18; and altered the expression of anti-inflammatory molecules including TGFßR1 in the hippocampus and cerebellum, though some differences were observed between males and females and the two brain regions. The anti-inflammatory pioglitazone inhibited ethanol-induced alterations in the expression of most, but not all, inflammation-related molecules.Conclusion: Chronic plus binge administration of ethanol induced the expression of inflammatory molecules in adult mice and pioglitazone suppressed ethanol-induced neuroinflammation.
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Alcoholismo , Etanol , Ratones , Femenino , Masculino , Animales , Etanol/farmacología , Pioglitazona/metabolismo , Pioglitazona/farmacología , Enfermedades Neuroinflamatorias , Hipocampo , Cerebelo/metabolismoRESUMEN
BACKGROUND: AAPM Task Group (TG) 275 was charged with developing practical, evidence-based recommendations for physics plan and chart review clinical processes for radiation therapy. As part of this charge, and to characterize practices and clinical processes, a survey of the medical physics community was developed and conducted. Detailed analyses and trends based on the survey that exceeded TG report length constraints are presented herein. AIMS: The design, development, and detailed results of the TG- 275 survey as well as statistical analysis and trends are described in detail. This is complementary material to the TG 275 report. METHODS AND MATERIALS: The survey consisted of 100 multiple-choice questions divided into four main sections: 1) Demographics, 2) Initial Plan Check, 3) On-Treatment, and 4) End-of-Treatment Chart Check. The survey was released to all AAPM members who self-reported working in the radiation oncology field, and it was kept open for 7 weeks. Results were summarized using descriptive statistics. To study practice differences, tests of association were performed using data grouped by four demographic questions: 1) Institution Type, 2) Average number of patients treated daily, 3) Radiation Oncology Electronic Medical Record, and 4) Perceived Culture of Safety. RESULTS: The survey captured 1370 non-duplicate entries from the United States and Canada. Differences across practices were grouped and presented based on Process-Based and Check-Specific questions. A risk-based summary was created to show differences amongst the four demographic questions for checks associated with the highest risk failure modes identified by TG-275. CONCLUSION: The TG-275 survey captured a baseline of practices on initial plan, on-treatment, and end-of-treatment checks across a wide variety of clinics and institutions. The results of test of association showed practice heterogeneities as a function of demographic characteristics. Survey data were successfully used to inform TG-275 recommendations.
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Oncología por Radiación , Humanos , Estados Unidos , Encuestas y Cuestionarios , CanadáRESUMEN
The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the US. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the US. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: Must and must not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. While must is the term to be used in the guidelines, if an entity that adopts the guideline has shall as the preferred term, the AAPM considers that must and shall have the same meaning. Should and should not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances.
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Física Sanitaria , Oncología por Radiación , Humanos , Estados Unidos , Física Sanitaria/educación , Lista de Verificación , SociedadesRESUMEN
The American Association of Physicists in Medicine began the Medical Physics Leadership Academy Journal Club in the fall of 2020. The initiative was launched to provide a forum for medical physicists to learn about leadership topics using published material, discuss and reflect on the material, and consider incorporating the discussed skills into their professional practice. This report presents the framework for the MPLA Journal Club program, describes the lessons learned over the last 2 years, summarizes the data collected from attendees, and highlights the roadmap for the program moving forward.