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BACKGROUND: Gastric cancer is the 5th most common malignancy worldwide. Surgical treatment for the disease can often be highly morbid, especially in elderly patients. The modified 5-item frailty index (mFI-5), a recently developed tool for assessing patient frailty, has been shown to be an effective predictor of post-operative outcomes in various surgical fields. This study aims to assess the utility of the mFI-5 in predicting adverse postoperative outcomes following gastrectomy for gastric cancer. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried for patients who underwent partial or total gastrectomy for gastric cancer between 2011 and 2021. The mFI-5 score was calculated based on the presence of hypertension, congestive heart failure, diabetes mellitus, chronic obstructive pulmonary disease, and partially or fully dependent functional status. Patients were stratified into 3 groups according to mFI-5 score (mFI-5 = 0, mFI-5 = 1, mFI-5 ≥ 2). Univariate analysis and multivariate logistic regression were used to evaluate the association between mFI-5 score and post-operative outcomes. RESULTS: 7438 patients were identified (mFI-5 = 0: 3032, mFI-5 = 1: 2805, mFI-5 ≥ 2: 1601). mFI-5 ≥ 2 was an independent predictor of overall complications (OR 1.43, p < 0.001), serious complications (OR 1.42, p < 0.001), pneumonia (OR 1.43, p = 0.010), MI (OR 2.91, p = 0.005), and readmission within 30 days (OR 1.33, p = 0.008). Patients with higher frailty were more likely to experience unplanned intubation (OR 2.06, p < 0.001; OR 2.47, p < 0.001), failure to wean from the ventilator (OR 1.68, p = 0.003; OR 2.00, p < 0.001), acute renal failure (OR 3.25, p = 0.003; OR 3.27, p = 0.005), 30-day mortality (OR 1.73, p = 0.009; OR 1.94, p = 0.004), and non-home discharge (OR 1.34, p = 0.001; OR 1.74, p < 0.001) relative to non-frail patients. CONCLUSION: Higher frailty, as indicated by an increased mFI-5 score, raises the risk of serious post-operative complications in patients with gastric cancer undergoing gastrectomy. The mFI-5 has the potential to help identify high-risk patients and enhance pre-operative discussions and optimization.
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Liver tests are commonly performed in primary care and may signal the presence of acute or chronic liver disease. Abnormal results are defined by standardized rather than individual laboratory thresholds and must be interpreted in the context of a patient's history and examination. The pattern and severity of liver injury may provide clues about the cause of disease and should guide diagnostic evaluation with serologic testing and liver imaging. A systematic, stepwise approach to the evaluation and management of abnormal liver test results is recommended to optimize high-value care.
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Hepatopatías/diagnóstico , Hepatopatías/terapia , Pruebas de Función Hepática , Atención Primaria de Salud , Biomarcadores/análisis , Diagnóstico Diferencial , Humanos , Anamnesis , Examen Físico , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Female researchers are underrepresented in academic surgery. While they are increasingly producing original research, they lag male researchers in productivity. This disparity is not well understood within the nascent field of global surgery. The following study examines gender parity in global surgery research presented at the Academic Surgical Congress and within subsequent publications. METHODS: Abstracts presented at the Academic Surgical Congress (ASC) between 2015 and 2019 in "Global Surgery" sessions were reviewed to obtain title, the first author (FA) and senior author (SA). The authors were classified by gender. The Scopus database was queried by two reviewers for abstracts with corresponding publications, citations, and journal impact factors. Statistical analysis was conducted using chi-square analysis and t-tests where appropriate. RESULTS: Of a total of 6635 abstracts, 218 global surgery abstracts over a 5-year period were identified. Of these abstracts, 96 (44%) had female FAs, while 56 (26%) had female SAs. When comparing gender, female (44%) FAs and male (56%) FAs were equally represented. While SAs were significantly less likely to be female (26% versus 74%, P < 0.0001), female senior authorship increased significantly within the study period. Output with respect to publications, citations, and journal impact factors were equal by gender. CONCLUSIONS: This study presents 5 y of gender trends in global surgery scholarly work presented at the ASC. Despite an overall predominance of male senior authors, the paradigm is shifting with a recent trend to gender parity. Male and female authors have equal output and are equally impactful. Findings of gender equity in academic global surgery are encouraging, and further study of other disciplines are warranted.
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Congresos como Asunto/estadística & datos numéricos , Identidad de Género , Cirugía General/estadística & datos numéricos , Salud Global/estadística & datos numéricos , Femenino , Humanos , MasculinoRESUMEN
We investigated the relationships among chronic violence exposure, post-traumatic stress disorder (PTSD) symptom severity, hopelessness, substance use, and perpetuation of violence to facilitate the development of trauma-related interventions for residents of Newark, NJ. A convenience sample of Newark residents (N = 153) was recruited from community centers during various events in 2016-2017. Anonymous, self-report survey measures included a PTSD screen (PCL-C), Beck's Hopelessness Scale, the CAGE questionnaire, and a CDC Health Behavior Scale. Descriptive statistics, Pearson's correlations, Chi square analyses, logistic, and linear regressions were used for analysis. Thirty percent (95% CI [22.7, 37.4]) of our sample screened positive for PTSD. Drug and alcohol use, fighting, and hopelessness were related to severity of PTSD symptoms (p < 0.05). Female gender, CAGE scores, and hopelessness predicted the severity of PTSD symptoms (R2 = 0.354, p < 0.05). Our data has informed the development of a resilience support group currently in the pilot stage for community members.
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Trastornos por Estrés Postraumático , Trastornos Relacionados con Sustancias , Femenino , Humanos , Autoimagen , Trastornos por Estrés Postraumático/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Encuestas y Cuestionarios , ViolenciaRESUMEN
BACKGROUND: Basic bleeding control (BCon) techniques can save lives globally but the knowledge is not widespread in low-income countries where trauma is a common cause of death. Short-term surgical missions (STSMs) are an effective route to share this public health initiative around the world. MATERIALS AND METHODS: Over 2017-2018, the International Surgical Health Initiative organized STSMs to locations in Sierra Leone, Bangladesh, Peru, and Ghana. The hour-long official American College of Surgeons Basic Bleeding Control course was offered to host participants several times over the course of the mission. Data including number and size of classes, type of trainee, instructors trained, and success rate in demonstrating acquisition of core BCon principles and techniques were collected. RESULTS: Over the course of four, week-long STSMs, 748 people were successfully trained in BCon over 27 sessions, with an average of 28 trainees and up to four instructors per class. One-hundred percent of trainees demonstrated acquisition of required skills proficiency. Trainees included health care workers and those in public security roles. CONCLUSIONS: Concurrent with a short-term surgical mission, a substantial number of health care providers and would-be bystanders can be trained in BCon in countries most impacted by trauma. Local instructors can be trained to teach BCon independently to sustain the initiative. STSMs are a feasible modality to teach bleeding control techniques to an international audience that does not have rapid access to effective prehospital care.
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Personal de Salud/educación , Hemorragia/terapia , Técnicas Hemostáticas , Misiones Médicas/organización & administración , Heridas y Lesiones/complicaciones , Altruismo , Países en Desarrollo , Estudios de Factibilidad , Femenino , Hemorragia/etiología , Humanos , Evaluación de Programas y Proyectos de SaludRESUMEN
BACKGROUND: Workforce trends in surgery demonstrate persistent gender inequity. Humanitarian surgical outreach opportunities exist for surgeons; however, it is unclear as to whether gender disparities exist in this arena. This pilot study examines gender equity among volunteer surgeons using a decade of compiled data from a surgical nongovernmental organization (NGO) that hosts multinational surgical outreach. We aim to evaluate gender proportions among surgical volunteers, compare the gender profiles of NGO surgeons with local and nationwide cohorts, and examine the productive output of surgical volunteers by gender. MATERIALS AND METHODS: A retrospective review was conducted of the records of the International Surgical Health Initiative, an NGO that hosts short-term surgical missions, to generate a demographic roster of volunteers between 2009 and 2018. Comparisons were made of gender profiles within volunteer cohorts against local institutional data and nationwide surgical workforce data. Productivity outputs of surgical volunteers were compared. Chi-square tests and Wilcoxon two-sample statistical t-tests were used. RESULTS: A total of 23 short-term surgical trips were inclusive of 227 volunteers, and 61% (139) were female. Physicians were less likely to be female than other volunteers. In addition, nonsurgical volunteers were more likely to be female compared with surgical volunteers (67% versus 44%, P < 0.01). No gender differences were observed by average number of trips or propensity for repeat trips among surgical volunteers. No differences were found in proportions of female surgical attendings and residents in the NGO cohort compared with the local and national cohorts. CONCLUSIONS: Females contribute substantially to surgical outreach, representing more than half the volunteers in this organization. Gender profiles of female surgeons in this NGO are in parity with those of surgical attendings and residents in the national census. Male and female volunteer surgeons are equally productive. There is an equitable gender representation among volunteer surgeons in this NGO. Further studies of other surgical organizations participating in surgical outreach are required toward a more complete understanding of female participation in international humanitarian efforts.
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Altruismo , Fuerza Laboral en Salud , Cirujanos , Femenino , Humanos , Masculino , Proyectos Piloto , Estudios Retrospectivos , Caracteres Sexuales , VoluntariosRESUMEN
OBJECTIVEAlthough parasitic infections are endemic to parts of the developing world and are more common in areas with developing economies and poor sanitary conditions, rare cases may occur in developed regions of the world.METHODSArticles eligible for the authors' literature review were initially searched using PubMed with the phrases "parasitic infections" and "spine." After the authors developed a list of parasites associated with spinal cord infections from the initial search, they expanded it to include individual diagnoses, using search terms including "neurocysticercosis," "schistosomiasis," "echinococcosis," and "toxoplasmosis."RESULTSTwo recent cases of parasitic spinal infections from the authors' institution are included.CONCLUSIONSKey findings on imaging modalities, laboratory studies suggestive of parasitic infection, and most importantly a thorough patient history are required to correctly diagnose parasitic spinal infections.
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Equinococosis/parasitología , Parásitos/patogenicidad , Enfermedades Parasitarias/etiología , Columna Vertebral/parasitología , Animales , Países en Desarrollo , Humanos , Enfermedades Parasitarias/diagnóstico , Enfermedades Parasitarias/terapia , Columna Vertebral/fisiopatologíaRESUMEN
BACKGROUND: Treatment of hepatitis C virus (HCV) with direct-acting antiviral (DAA) regimens has resulted in high rates of sustained virologic response (SVR). Treatment of vulnerable populations may be improved by incorporating an on-site intensive specialty pharmacy (ON-ISP). AIMS: To describe outcomes of HCV treatment at a safety-net hospital and proportion of subjects achieving SVR for those using the ON-ISP compared to an off-site pharmacy (OFF-SP). METHODS: A retrospective cohort study of 219 subjects treated for HCV with DAA at Boston Medical Center was conducted. Subject characteristics, virologic response, and pharmacy services used were recorded. We used multivariable logistic regression to test the association between ON-ISP and SVR after adjusting for covariates. RESULTS: SVR occurred in 71% of subjects by intention-to-treat (73% among ON-ISP users vs 57% among OFF-SP users) and 95% completing treatment per-protocol (96% among ON-ISP users vs 87% among OFF-SP users). Adjustment for age, sex, ethnicity, insurance, fibrosis, prior treatment, and MELD revealed an increased likelihood of SVR among users of ON-ISP: OR 6.0 (95% CI 1.18-31.0). No significant difference in treatment delay or adverse events was seen among users of either pharmacy type. CONCLUSIONS: HCV treatment with DAA was well tolerated, but the rate of SVR was low (71%) compared to trials. This was due to loss to follow-up, as the per-protocol rate of SVR was much higher (95%). Use of ON-ISP was associated with an increase in SVR and may be valuable for improving care for vulnerable populations.
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Antivirales/uso terapéutico , Hepacivirus , Hepatitis C , Servicios Farmacéuticos , Femenino , Hepacivirus/efectos de los fármacos , Hepacivirus/aislamiento & purificación , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Humanos , Perdida de Seguimiento , Masculino , Persona de Mediana Edad , Servicios Farmacéuticos/estadística & datos numéricos , Servicios Farmacéuticos/provisión & distribución , Mejoramiento de la Calidad/organización & administración , Estudios Retrospectivos , Respuesta Virológica Sostenida , Estados Unidos/epidemiología , Poblaciones Vulnerables/estadística & datos numéricosRESUMEN
Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons. We generated transgenic mice lacking subdomain 2 of Baf53b (BAF53bΔSB2). Long-term synaptic potentiation (LTP) and long-term memory, both of which are associated with phosphorylation of the actin severing protein cofilin, were assessed in these animals. A phosphorylation mimic of cofilin was stereotaxically delivered into the hippocampus of BAF53bΔSB2 mice in an effort to rescue LTP and memory. BAF53bΔSB2 mutant mice show impairments in phosphorylation of synaptic cofilin, LTP, and memory. Both the synaptic plasticity and memory deficits are rescued by overexpression of a phosphorylation mimetic of cofilin. Baseline physiology and behavior were not affected by the mutation or the experimental treatment. This study suggests a potential link between nBAF function, actin cytoskeletal remodeling at the dendritic spine, and memory formation. This work shows that a targeted manipulation of synaptic function can rescue adult plasticity and memory deficits caused by manipulations of nBAF, and thereby provides potential novel avenues for therapeutic development for multiple intellectual disability disorders.
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Ensamble y Desensamble de Cromatina/genética , Proteínas Cromosómicas no Histona/metabolismo , Memoria/fisiología , Mutación/genética , Plasticidad Neuronal/genética , Fosfopiruvato Hidratasa/metabolismo , Factores Despolimerizantes de la Actina/genética , Factores Despolimerizantes de la Actina/metabolismo , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Nucléolo Celular/metabolismo , Proteínas Cromosómicas no Histona/genética , Hipocampo/citología , Hipocampo/metabolismo , Técnicas In Vitro , Potenciación a Largo Plazo/genética , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Red Nerviosa/fisiología , Neuronas/ultraestructura , Fosfopiruvato Hidratasa/genética , Fosforilación/genética , Eliminación de Secuencia/genética , Transducción GenéticaRESUMEN
The role of transition metals in the formation and aging of secondary organic aerosol (SOA) from aliphatic and aromatic precursors in heterogeneous/multiphase reactions is not well understood. The reactivity of soluble Fe(III) toward known benzene photooxidation products that include fumaric (trans-butenedioic) and muconic (trans,trans-2,4-hexadienedioic) acids was investigated. Efficient formation of brightly colored nanoparticles was observed that are mostly rod- or irregular-shaped depending on the structure of the organic precursor. The particles were characterized for their optical properties, growth rate, elemental composition, iron content, and oxidation state. Results indicate that these particles have mass absorption coefficients on the same order as black carbon and larger than that of biomass burning aerosols. The particles are also amorphous in nature and consist of polymeric chains of Fe centers complexed to carboxylate groups. The oxidation state of Fe was found to be in between Fe(III) and Fe(II) in standard compounds. The organic reactant to iron molar ratio and pH were found to affect the particle growth rate. Control experiments using maleic acid (cis-butenedioic acid) and succinic acid (butanedioic acid) produced no particles. The formation of particles reported herein could account for new pathways that lead to SOA and brown carbon formation mediated by transition metals. In addition, the multiple chemically active components in these particles (iron, organics, and acidic groups) may have an effect on their chemical reactivity (enhanced uptake of trace gases, catalysis, and production of reactive oxygen species) and their likely poor cloud/ice nucleation properties.
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Ácidos Dicarboxílicos , Compuestos Férricos , Nanopartículas , Polímeros , AerosolesRESUMEN
PURPOSE: Following laparoscopic anti-reflux surgery (LARS), recurrence of hiatal hernia is common. Patients with symptomatic recurrence typically undergo revision of the fundoplication or conversion to magnetic sphincter augmentation (MSA) in addition to cruroplasty. However, patients with an intact fundoplication or MSA may only require repeat cruroplasty to repair their recurrent hiatal hernia. The purpose of this study is to compare outcomes following cruroplasty alone compared to full revision (i.e. redo fundoplication or MSA with cruroplasty) for the management of recurrent hiatal hernias. METHODS: A retrospective review of patients undergoing surgical revision of a symptomatic recurrent hiatal hernia between February 2009 and October 2022 was performed. Preoperative characteristics, intraoperative details, and postoperative outcomes were compared between patients undergoing cruroplasty alone versus full revision. RESULTS: A total of 141 patients were included in the analysis. 93 patients underwent full revision, and 48 patients underwent cruroplasty alone. The mean time between initial and revisional surgery was 8 ± 7.7 years. There was no significant difference in operative time or rates of intra-operative or post-operative complication between groups. Patients undergoing cruroplasty alone had a mean Gastroesophageal Reflux Disease Health Related Quality Life (GERD-HRQL) Questionnaire score of 9.6 ± 10.2 compared to a mean score of 8.9 ± 11.2 for full revision patients (p = 0.829). Recurrence rates following revision was 10.4% for cruroplasty alone patients and 11.8% in full revision patients (p > 0.999). CONCLUSION: In patients with intact fundoplication or MSA, cruroplasty alone results in similar post-operative outcomes compared to full revision for recurrent hiatal hernia.
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BACKGROUND: Foreign accent syndrome is a rare but potentially devastating clinical condition associated with altered speech rhythm and prosody, often occurring after a cerebral vascular accident. Missing this diagnosis can lead to delayed stroke work-up and treatment. OBJECTIVE: We report a case of foreign accent syndrome in a 60-year-old woman who presented to the Emergency Department (ED) with 3 weeks of altered speech pattern, widened gait, bilateral leg heaviness, and mild headache. CASE REPORT: The patient had a history of Type 2 diabetes, malignant hypertension, toxic nodular goiter, and hyperlipidemia. She initially presented to the ED at the onset of symptoms, was thought to have had speech change secondary to a goiter impinging on the recurrent laryngeal nerve, and was discharged. She returned to the ED 3 weeks later when outpatient imaging revealed subacute infarction of the left hemi-pons and absent flow within the left vertebral artery. On examination, the patient was alert and conversational. She spoke fluently with an accent that had components of Jamaican and the accent of an Italian speaking English. Neurology was consulted and the patient was admitted. The patient was treated medically, and was discharged home with primary care follow-up. She developed a second, more significant stroke 1 month later, with unilateral weakness and slurred speech in the middle cerebral artery distribution. CONCLUSION: Clinicians should be aware that some stroke patients present with various atypical symptoms, and should suspect stroke in any patient with acute-onset neurological symptoms, including speech change.
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Trastornos de la Articulación/etiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Femenino , Trastornos Neurológicos de la Marcha/etiología , Cefalea/etiología , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , SíndromeRESUMEN
Glaucoma is a chronic and progressive eye disease, commonly associated with elevated intraocular pressure (IOP) and characterized by optic nerve degeneration, cupping of the optic disc, and loss of retinal ganglion cells (RGCs). The pathological changes in glaucoma are triggered by multiple mechanisms and both mechanical effects and vascular factors are thought to contribute to the etiology of glaucoma. Various studies have shown that endothelin-1 (ET-1), a vasoactive peptide, acting through its G protein coupled receptors, ETA and ETB, plays a pathophysiologic role in glaucoma. However, the mechanisms by which ET-1 contribute to neurodegeneration remain to be completely understood. Our laboratory and others demonstrated that macitentan (MAC), a pan endothelin receptor antagonist, has neuroprotective effects in rodent models of IOP elevation. The current study aimed to determine if oral administration of a dual endothelin antagonist, macitentan, could promote neuroprotection in an acute model of intravitreal administration of ET-1. We demonstrate that vasoconstriction following the intravitreal administration of ET-1 was attenuated by dietary administration of the ETA/ETB dual receptor antagonist, macitentan (5 mg/kg body weight) in retired breeder Brown Norway rats. ET-1 intravitreal injection produced a 40% loss of RGCs, which was significantly lower in macitentan-treated rats. We also evaluated the expression levels of glial fibrillary acidic protein (GFAP) at 24 h and 7 days post intravitreal administration of ET-1 in Brown Norway rats as well as following ET-1 treatment in cultured human optic nerve head astrocytes. We observed that at the 24 h time point the expression levels of GFAP was upregulated (indicative of glial activation) following intravitreal ET-1 administration in both retina and optic nerve head regions. However, following macitentan administration for 7 days after intravitreal ET-1 administration, we observed an upregulation of GFAP expression, compared to untreated rats injected intravitreally with ET-1 alone. Macitentan treatment in ET-1 administered rats showed protection of RGC somas but was not able to preserve axonal integrity and functionality. The endothelin receptor antagonist, macitentan, has neuroprotective effects in the retinas of Brown Norway rats acting through different mechanisms, including enhancement of RGC survival and reduction of ET-1 mediated vasoconstriction.
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STUDY DESIGN: Descriptive review article. OBJECTIVE: The purpose of this article is to provide guidelines and recommendations for how to safely resume dental and craniomaxillofacial STSMs. The following considerations will be discussed: the need for extensive collaboration between organizations and local leadership, the importance of COVID-19 testing, use and management of personal protective equipment, team selection and training, social distancing protocols, and criteria for patient and case selection. METHODS: A literature review was completed, identifying resources and current data regarding the safe resumption clinical activities during the COVID-19 pandemic. RESULTS: At this time, there are no protocols developed regarding the safe resumption of STSMs. Primary resources, including the CDC, WHO, and FDA should be closely monitored so that developed protocols from these recommendations reflect the latest information. CONCLUSION: This paper outlines general considerations and recommendations for dentists, oral health specialists, and craniomaxillofacial surgeons seeking to safely resume STSMs. These recommendations are designed to minimize the risk of exposure to COVID-19 by reinforcing social distancing protocols, reviewing criteria for patient and case selections, encouraging collaboration between organizations and local leadership, and team training. These guidelines should be tailored to fit the needs of each individual mission while keeping the safety as the main objective.
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INTRODUCTION AND LEADERSHIP FRAMEWORK: Leadership development has emerged as an essential component of pharmacy school curricula. Recognizing the need for curricular integration of leadership and teaming throughout each year, the University of Utah implemented a longitudinal leadership framework called Relational Leadership. 5 Dynamics was used as a tool to teach concepts of effective teamwork and leadership in different courses within this framework. EDUCATIONAL CONTEXT AND METHODS: 5 Dynamics was used within two courses in the curricula. 5 Dynamics is designed to enhance self-awareness and improve team skills by providing a detailed assessment of how each student prefers to work and collaborate and how their respective preferences or energies can be utilized in a team setting. Learning outcomes were assessed using the Team Performance Survey. FINDINGS AND DISCUSSION: Each student was provided with an individualized energy profile from 5 Dynamics and used their particular energies to complete various activities, assignments, and projects. The highest energy was Examine, with 61% of students being either "effortless" or "abundant". A total of 64% of students reported they strongly agreed with the statement that they understood how to apply their 5 Dynamics results to learning, work, and collaboration. Student survey scores from the Team Performance Survey administered at the end of each course indicated high-quality team interactions between students. IMPLICATIONS: 5 Dynamics is a tool that may help students in maximizing their leadership and teamwork skills. This tool may be utilized by other institutions in diverse courses to teach concepts of teaming, leadership, and self-awareness.
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Curriculum , Liderazgo , Humanos , Aprendizaje , Percepción , EstudiantesRESUMEN
BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed the management of advanced malignancies but are associated with diarrhea and colitis. The objective of our systematic review and meta-analysis was to determine the incidence and outcomes of ICI-associated diarrhea and colitis. Bibliographic databases were searched through August 13, 2019, for observational studies of ICI therapy reporting the incidence and/or treatment of diarrhea or colitis. The primary outcome was ICI-associated diarrhea and colitis. Meta-analyses were performed with random-effects models. Twenty-five studies (N=12,661) were included. All studies had a high risk of bias in at least 1 domain. The overall incidence of diarrhea/colitis was 12.8% [95% confidence interval (CI), 8.8-18.2, I2=96.5]. The incidence was lower in patients treated with anti-programmed cell death 1/programmed death-ligand 1 (4.1%, 95% CI, 2.6-6.5) than in those treated with anti-cytotoxic T-cell lymphocyte-associated antigen 4 (20.1%, 95% CI, 15.9-25.1). The remission of diarrhea and/or colitis was higher in patients treated with corticosteroids plus biologics (88.4%, 95% CI, 79.4-93.8) than in those treated with corticosteroids alone (58.3%, 95% CI, 49.3-66.7, Q=18.7, P<0.001). ICI were permanently discontinued in 48.1% of patients (95% CI, 17.8-79.1). ICI were restarted after temporary interruption in 48.6% of patients (95% CI, 18.2-79.4) of whom 17.0% (95% CI, 6.4-30.0) experienced recurrence. Real-world incidence of ICI-associated diarrhea/colitis exceeds 10%. These events lead to permanent ICI discontinuation in just over 50% of patients, while <20% have recurrence of symptoms if ICI are resumed. Further studies are needed to identify patients who would benefit from early treatment with biologics as well as appropriate patients to resume ICI therapy.
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Colitis/inducido químicamente , Diarrea/inducido químicamente , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Corticoesteroides/uso terapéutico , Productos Biológicos/uso terapéutico , Colitis/tratamiento farmacológico , Colitis/epidemiología , Diarrea/tratamiento farmacológico , Diarrea/epidemiología , Humanos , Incidencia , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Estudios Observacionales como AsuntoRESUMEN
Chronic hepatitis C virus infection remains a national and global public health burden and is associated with significant morbidity and mortality. Oral direct-acting antiviral combination regimens have excellent tolerability and efficacy with rates exceeding 90%. Sustained virologic response is associated with significant improvements in clinical outcomes. However, translation of sustained virologic response rates from trials to community settings has been poor with interferon-based regimens. We review and summarize key datasets from major real-world observational cohort studies. We review preliminary data from oral generic direct-acting antiviral formulations. Future real-world studies are needed to further clarify optimal treatment strategies for difficult-to-treat populations.
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Antivirales/uso terapéutico , Medicamentos Genéricos/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Administración Oral , Antivirales/administración & dosificación , Estudios de Cohortes , Quimioterapia Combinada , Medicamentos Genéricos/administración & dosificación , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/virología , Humanos , Estudios Observacionales como Asunto , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
Subcapsular liver hematoma (SLH) is a rare condition that is associated with preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. A high level of suspicion, early diagnosis, and coordinated, intensive multidisciplinary management are necessary to monitor for serious complications and prevent death. Options include conservative management, hepatic resection, hepatic artery ligation and liver transplantation. This paper describes a 34-year-old woman with HELLP syndrome who developed a large grade III SLH that was managed conservatively.
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Histone acetylation is a fundamental epigenetic mechanism that is dynamically regulated during memory formation. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) compete to modulate histone acetylation, allowing for rapid changes in acetylation in response to a learning event. HDACs are known to be powerful negative regulators of memory formation, but it is not clear whether this function depends on HDAC enzymatic activity per se. Here, we tested whether the enzymatic activity of an individual Class I HDAC, HDAC3, has a role in fear memory formation in subregions of the hippocampus and amygdala. We found that fear conditioning drove expression of the immediate early genes cFos and Nr4a2 in the hippocampus, which coincided with reduced HDAC3 occupancy at these promoters. Using a dominant-negative, deacetylase-dead point mutant virus (AAV-HDAC3(Y298H)-v5), we found that selectively blocking HDAC3 deacetylase activity in either the dorsal hippocampus or basal nucleus of the amygdala enhanced context fear without affecting tone fear. Blocking HDAC3 activity in the lateral nucleus of the amygdala, on the other hand, enhanced tone, but not context fear memory. These results show for the first time that the enzymatic activity of HDAC3 functions to negatively regulate fear memory formation. Further, HDAC3 activity regulates different aspects of fear memory in the basal and lateral subregions of the amygdala. Thus, the deacetylase activity of HDAC3 is a powerful negative regulator of fear memory formation in multiple subregions of the fear circuit.
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Complejo Nuclear Basolateral/fisiología , Condicionamiento Clásico/fisiología , Miedo/fisiología , Hipocampo/fisiología , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/fisiología , Memoria/fisiología , Animales , Percepción Auditiva/efectos de los fármacos , Percepción Auditiva/fisiología , Complejo Nuclear Basolateral/efectos de los fármacos , Complejo Nuclear Basolateral/metabolismo , Condicionamiento Clásico/efectos de los fármacos , Miedo/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Memoria/efectos de los fármacos , Ratones , Ratones Endogámicos C57BLRESUMEN
A 65-year-old man with metastatic melanoma was started on immunotherapy, switched to alternative targeted therapy and developed disseminated intravascular coagulation. This case underscores the complexity of interpreting and managing side effects of novel therapies in cancer care, identification of progression versus pseudoprogression and challenges in sequencing treatments in metastatic melanoma.