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Resumen: El término colestasis se refiere a la retención de ácidos biliares ya sea dentro del hepatocito o en los ductos biliares de cualquier calibre. Por laboratorio, se define por la elevación de fosfatasa alcalina arriba de 1.67 veces su valor normal. Las enfermedades colestásicas pueden asociarse a un proceso inflamatorio de la glándula hepática que provoca destrucción de los hepatocitos (hepatitis), a ictericia (coloración amarillenta de piel y mucosas asociada a elevación en niveles séricos de bilirrubinas) o ambas, aunque estos tres conceptos no deben considerarse sinónimos. Los padecimientos colestásicos pueden clasificarse como intra o extrahepáticos dependiendo de su etiología, y esto es importante para elegir los estudios diagnósticos adecuados y la terapéutica indicada en cada uno de los casos. Una historia clínica completa, aunada a exploración física exhaustiva y estudios iniciales básicos como el ultrasonido hepático y las pruebas de funcionamiento del hígado, pueden ayudar al clínico a decidir el camino a seguir al enfrentarse al paciente con colestasis. La Asociación Mexicana de Hepatología, la Asociación Mexicana de Gastroenterología y la Asociación Mexicana de Endoscopia Gastrointestinal decidieron trabajar en el primer posicionamiento científico mexicano sobre este tema. Abstract: The term cholestasis refers to bile acid retention, whether within the hepatocyte or in the bile ducts of any caliber. Biochemically, it is defined by a level of alkaline phosphatase that is 1.67-times higher than the upper limit of normal. Cholestatic diseases can be associated with an inflammatory process of the liver that destroys hepatocytes (hepatitis), with jaundice (yellowing of the skin and mucus membranes, associated with elevated serum bilirubin levels), or with both, albeit the three concepts should not be considered synonymous. Cholestatic diseases can be classified as intrahepatic or extrahepatic, depending on their etiology. Knowing the cause of the condition is important for choosing the adequate diagnostic studies and appropriate treatment in each case. A complete medical history, together with a thorough physical examination and basic initial studies, such as liver ultrasound and liver function tests, aid the clinician in deciding which path to follow, when managing the patient with cholestasis. In a joint effort, the Asociación Mexicana de Hepatología (AMH), the Asociación Mexicana de Gastroenterología (AMG) and the Asociación Mexicana de Endoscopia Gastrointestinal (AMEG) developed the first Mexican scientific position statement on said theme.

Background: Fluoxetine (FLX) represents the antidepressant of choice for the management of pediatric mood-related illnesses. Accumulating preclinical evidence suggests that ontogenic FLX exposure leads to deregulated affect-related phenotypes in adulthood. Mood-related symptomatology constitutes a risk-factor for various neurological disorders, including Alzheimer’s disease (AD), making it possible for juvenile FLX history to exacerbate the development of neurodegenerative diseases. Objective: Because AD is characterized by the pathological accumulation of hyperphosphorylated tau, which can result from impaired function of protein degradation pathways, such as autophagy and the ubiquitin-proteasome system (UPS), we evaluated the long-term effects of adolescent FLX exposure on these pathways, using mice as a model system. Methods: We subjected C57BL/6 adolescent male mice to FLX (20 mg/kg/day) from postnatal day (PD) 35 to PD49. Twenty-one days after the last FLX injection (i.e., adulthood; PD70), mice were euthanized and, using immunoblotting analysis, we evaluated protein markers of autophagy (Beclin-1, LC3-II, p62) and the UPS (K48-pUb), as well as AD-associated forms of phosphorylated tau, within the hippocampus and prefrontal cortex. Results: Juvenile FLX pre-exposure mediated long-term changes in the expression of protein markers (increased LC3-II and decreased p62) that is consistent with autophagy activation, particularly in the prefrontal cortex. Furthermore, FLX history induced persistent accumulation of AD-associated variants of tau in both the hippocampus and prefrontal cortex Conclusion: Adolescent FLX treatment may have enduring effects in the neuronal protein degradation machinery, which could adversely influence clearance of abnormal proteins, potentially predisposing individuals to developing AD in later life.

Nonalcoholic steatohepatitis (NASH), a chronic liver disease without an approved therapy, is associated with lipotoxicity and insulin resistance and is a major cause of cirrhosis and hepatocellular carcinoma. Aramchol, a partial inhibitor of hepatic stearoyl-CoA desaturase (SCD1) improved steatohepatitis and fibrosis in rodents and reduced steatosis in an early clinical trial. ARREST, a 52-week, double-blind, placebo-controlled, phase 2b trial randomized 247 patients with NASH (n = 101, n = 98 and n = 48 in the Aramchol 400 mg, 600 mg and placebo arms, respectively; NCT02279524 ). The primary end point was a decrease in hepatic triglycerides by magnetic resonance spectroscopy at 52 weeks with a dose of 600 mg of Aramchol. Key secondary end points included liver histology and alanine aminotransferase (ALT). Aramchol 600 mg produced a placebo-corrected decrease in liver triglycerides without meeting the prespecified significance (−3.1, 95% confidence interval (CI) −6.4 to 0.2, P = 0.066), precluding further formal statistical analysis. NASH resolution without worsening fibrosis was achieved in 16.7% (13 out of 78) of Aramchol 600 mg versus 5% (2 out of 40) of the placebo arm (odds ratio (OR) = 4.74, 95% CI = 0.99 to 22.7) and fibrosis improvement by ≥1 stage without worsening NASH in 29.5% versus 17.5% (OR = 1.88, 95% CI = 0.7 to 5.0), respectively. The placebo-corrected decrease in ALT for 600 mg was −29.1 IU l−1 (95% CI = −41.6 to −16.5). Early termination due to adverse events (AEs) was

Disruption of bone homeostasis caused by metastatic osteolytic breast cancer cells increases inflammatory osteolysis and decreases bone formation, thereby predisposing patients to pathological fracture and cancer growth. Alteration of osteoblast function induces skeletal diseases due to the disruption of bone homeostasis. We observed increased activation of pERK1/2 in osteolytic breast cancer cells and osteoblasts in human pathological specimens with aggressive osteolytic breast cancer metastases. We confirmed that osteolytic breast cancers with high expression of pERK1/2 disrupt bone homeostasis via osteoblastic ERK1/2 activation at the bone-breast cancer interface. The process of inflammatory osteolysis modulates ERK1/2 activation in osteoblasts and breast cancer cells through dominant-negative MEK1 expression and constitutively active MEK1 expression to promote cancer growth within bone. Trametinib, an FDA-approved MEK inhibitor, not only reduced breast cancer-induced bone destruction but also dramatically reduced cancer growth in bone by inhibiting the inflammatory skeletal microenvironment. Taken together, these findings suggest that ERK1/2 activation in both breast cancer cells and osteoblasts is required for osteolytic breast cancer-induced inflammatory osteolysis and that ERK1/2 pathway inhibitors may represent a promising adjuvant therapy for patients with aggressive osteolytic breast cancers by altering the shared cancer and bone microenvironment.

Although motorcycle accidents are a leading cause of limb injury in Uganda, little is known about injury care quality at regional hospitals. This study measured the incidence of clinical adverse events (CAEs) and identified associated treatment barriers surrounding motorcycle-related isolated limb injuries at a regional hospital. A prospective descriptive study was conducted among patients with motorcycle-related isolated limb injuries at a Ugandan regional hospital between September 2017 and February 2018. Patients were surveyed upon admission and monitored throughout their course of treatment. Weight-bearing status and quality of life measures (EQ-5D) were assessed at four and 12 weeks. One hundred twenty-four participants enrolled. Of the total participants, 12% refused definitive treatment. Among 108 treated patients, six experienced CAEs: four wound infections, one amputation, and one death. At 12 weeks follow-up, the majority of patients had no difficulty with mobility, pain/discomfort, or self-care, but 51% endorsed challenges completing certain daily chores, and 40% of patients could ambulate without an assistive device with restoration of pre-fracture gait. Both longer hospital stays and poorer 12-week functional recovery were seen among patients sustaining open fracture (p

The decision to initiate anticoagulation in older adults with atrial fibrillation is complicated by the benefit of ischemic stroke prevention vs the risk of falls resulting in major bleeds. The objective of this study was to assess the impact of different treatments including direct oral anticoagulants on quality-adjusted life-years (QALYs) in patients aged 75 years and older with atrial fibrillation in the context of falls. A Markov decision process was constructed for older patients with atrial fibrillation taking no anti-thrombotic, aspirin, warfarin, rivaroxaban, and apixaban. Input probabilities for clinical events were estimated from the available literature. One-way and two-way sensitivity analyses were performed by measuring the impact of varying input probabilities of clinical events on QALY outcomes. The base-case scenario estimated that older adults treated with no anti-thrombotic, aspirin, warfarin, rivaroxaban, and apixaban had QALYs of 8.03, 8.69, 10.38, 11.02, and 11.56, respectively. The sensitivity analysis estimated that an older adult would need to fall over 45 (rivaroxaban) and 458 (apixaban) times per year for the QALY of a direct oral anticoagulant to be lower than that of aspirin. Older adults with atrial fibrillation benefit from stroke protection of anticoagulants, especially direct oral anticoagulants, even if they are at high risk of falls. Clinicians should not consider fall risk as a deciding factor for withholding anticoagulation in this population of patients.

Introduction Traditional cigarette use influences cost-benefit decision making by promoting impulsive choice. However, the impact of nicotine exposure via electronic nicotine delivery systems on impulsivity remains unclear. Hence, the present study examined the short- and long-term effects of nicotine vapor on impulsive choice. Methods Twenty-four adult male rats were trained in the delay discounting task to choose between small immediate food rewards and large delayed food rewards. After 24 days of training in the task rats were exposed to vapor containing either 0, 12, or 24 mg/mL of nicotine for 10 days. To validate inhalation of nicotine vapor serum cotinine levels were analyzed on exposure days 1, 5, and 10 using enzyme-linked immunosorbent assay. Following vapor exposure, rats were retrained in the discounting task until rats displayed stable responding and the effects of nicotine vapor on choice preference were assessed. Results Rats exposed to 12 and 24 mg/mL nicotine vapor displayed higher serum cotinine levels than control rats exposed to 0 mg/mL vapor. There were no differences in impulsive choice between any vapor exposure groups when tested 15 days after exposure, across 6 days of stable responding, suggesting that nicotine vapor does not have long lasting effects on impulsive choice. Interestingly, a subsequent nicotine vapor challenge revealed short-term increases in impulsive choice immediately following a single exposure to 24 mg/mL nicotine vapor, relative to choice preference immediately following exposure to 0 mg/mL vapor. Conclusions These results suggest that exposure to nicotine vapor causes immediate, short-term increases in impulsive choice. Implications E-cigarette use is increasing at an alarming rate, particularly among adolescents and young adults. This is concerning given the lack of research into the effects of nicotine vapor exposure on the brain and behavior. The present study describes a viable rodent model of human e-cigarette use and suggests that exposure to nicotine vapor produces short-term increases in impulsive choice.

The purpose of this study was to evaluate the readability of breast cancer online patient educational materials (OPEM) written in Spanish and to compare to equivalent English-language OPEM.The breast cancer-related terms cáncer de seno (breast cancer), detección de cáncer de seno (breast cancer screening), and biopsia de seno (breast biopsy) were queried using an online search engine. After each query, educational information related to the queried term was downloaded from each website appearing on the first five search engine result pages. Readability of Spanish-language OPEM was evaluated using the Crawford reading grade score. When available, equivalent English-language OPEM from the same website was then evaluated using the mean of five validated readability indices. Differences in readability, word count, and reading time between Spanish- and English-language OPEM were compared using an unpaired t test. The Fisher exact test was used to compare the proportion of websites meeting AMA recommendations for patient educational resources.Queries for cáncer de seno, detección de cáncer de seno, and biopsia de seno yielded 27, 31, and 30 results of term-specific OPEM. Equivalent English-language versions were available for 19 (70.4%), 18 (58.1%), and 20 (66.7%) websites, respectively. Spanish-language OPEM were written at a lower grade reading level than equivalent English-language versions overall (5.49 ± 0.50 versus 7.77 ± 1.95, P.01). Spanish-language OPEM were also more likely than English-language OPEM to meet AMA recommendations (82.9% versus 40.4%, P.01).Breast cancer-related Spanish-language OPEM were written at a significantly lower grade reading level compared with equivalent information written in English.

Health systems adopting a medical assistant clinical ladder program would do well to invest in program leaders. Nurse mentors tasked with leading advancement programs should formally advance their own coaching and mentoring skills. The following literature remarks describe potentially better practices for nurses who develop adult learners along advancement pathways. The proposed practice considerations may guide program leaders in equipping nurse leaders with basic mentorship fundamentals. The recommendations may be adapted to any health system's complex adaptive network.

Low birth weight is an indicator that allows predicting the probability of survival of a child. In fact, there is an exponential relationship between weight deficit, gestational age, and perinatal mortality. In addition, it is important to indicate that a percentage of term children (37 ≤ weeks of gestation ≤ 41) who have low birth weight present with various sequelae of variable severity –especially in the neurological sphere– and hence the importance of predicting the presentation of low birth weight. Multiple Logistic Regression is one of the most expressive and versatile statistical instruments available for data analysis in both clinical and epidemiology. Its origin dates to the sixties with the transcendent work of Cornfield, Gordon & Smith on the risk of suffering from coronary heart disease and, in the way we know it today, with the contribution of Walter & Duncan in which addresses the issue of estimating the probability of occurrence of a certain event based on several variables. Its use has been universalized and expanded since the early eighties, due to the computer facilities available since then. Quantitative approach. The study design corresponds to that of an analytical observational epidemiological study of cases and controls with directionality response variable→explanatory variables and with prospective temporality. One thousand eight hundred fifteen newborns were studied [178 (9.81%) cases and 1,637 (90.19%) controls], which corresponds to nine controls per case. All term newborns (37 ≤ weeks of gestation ≤ 41) with weights < 2,500 g and ≥ 2,500 g were defined, respectively, as a case and as a control. The values obtained from the β Exponents or Odds Ratios indicate the positive contribution (OR> 1) in ascending numerical order of the explanatory variables alcoholism (0.0018); low socioeconomic level (0.5694); initiation of prenatal care from or after the 20th week of gestation (0.6116); birth interval ≤ 24 months (0.7942); age at menarche ≤ 12 years (1.0792); “unmarried” marital status (1.0961); female gender of the product (1.1271); maternal weight < 50 kg (1.4700); history of abortion(s) (1.5407); number of deliveries = 1 (1.5524); number of prenatal visits ≤ 5 (1.5966); type of delivery or abdominal birth route (1.6169); smoking (2.2019); number of deliveries ≥ 5 (2.2714); maternal age ≤ 19 years (2.4827); maternal age ≥ 36 years (2.8070); pathological obstetric history (4.0735); pathological personal history (4.6475); and maternal height < 150 cm (5.5092).

Background Missed appointments can have an adverse impact on health outcomes by delaying appropriate imaging, which can be critical in influencing treatment decisions. Objective To assess for socioeconomic and imaging exam factors associated with missed appointments among children scheduled for diagnostic imaging. Materials and methods We retrospectively analyzed children (21 days (OR=3.7; 95% CI=2.9–4.8). The use of radiation, intravenous contrast agent or sedation was not associated with increased likelihood of missed appointments. Conclusion Expanding our knowledge of how different socioeconomic and imaging-related factors influence missed appointments among children can serve as a foundational step to better understand existing and emerging disparities and inform strategies to advance health equity efforts in radiology.

Objective We aimed to estimate the proportion of patients visiting the emergency department (ED) who were not up to date with cancer screening guidelines to assess the scope of need and potential impact of ED-based cancer screening interventions. Methods Adult participants from the 2015 National Health Interview Survey were included. Among patients nonadherent to national breast, colorectal, or lung cancer screening guidelines, the proportion of patients reporting an ED visit within the last year was estimated, accounting for complex survey sampling design features. Multiple variable logistic regression analyses were then conducted to evaluate the association between sociodemographic characteristics and screening adherence. Results Of screening eligible respondents, 17.2% of women nonadherent to mammography screening, 16.9% of patients nonadherent to colorectal cancer screening, and 25.0% of patients nonadherent to lung cancer screening reported at least one ED visit in the preceding year. Patients visiting the ED with postsecondary school education were more likely to be up to date with mammography screening than those without advanced education (odds ratio [OR] 1.45; 95% confidence interval [CI]: 1.21-1.74; P = .01). Patients without insurance were less likely than those with insurance to report being up to date with both mammography screening (OR 0.31; 95% CI: 0.21-0.48; P = .01) and colorectal cancer screening (OR 0.56; 95% CI: 0.34-0.93; P = .03). Discussion Opportunities to improve cancer screening adherence exist through ED-based preventative care interventions, which leverage multidisciplinary partnerships, including radiologists, to reach large volumes of patients who are not engaged in cancer screening.

Millions of patients undergo CT imaging examinations every year. These encounters may represent opportunities to improve colorectal cancer (CRC) screening rates among patients who have not received recommended CRC screening. Using a nationally representative cross-sectional survey, our purpose was to estimate the proportion of patients who have undergone CT examinations who have not received recommended CRC screening.Survey respondents aged 45-75 years in the 2015 National Health Interview Survey without history of CRC were included. Proportion of patients who have undergone CT examinations among those who have not received recommended CRC screening was estimated. Multiple variable logistic regression analyses were performed to evaluate the association between sociodemographic characteristics and CRC screening adherence. Analyses were conducted accounting for complex survey design features.Sixteen thousand two hundred and six survey respondents met inclusion criteria. About 44.3% (43.1, 45.5) reported having ever received a CT scan and 50.8% (49.6, 51.9) underwent CRC screening. Among those who previously had CT scans, Asian race participants and participants without health insurance coverage had lower odds of adherence, while increasing household income and education were associated with higher odds of adherence (P0.01). Among participants who did not receive CRC screening, 33.7% (32.1%, 35.3%) reported having a CT scan, representing an estimated 15,278,667 people across the United States.Among patients who have not received recommended CRC screening, nearly 1 out of 3 report having undergone a CT examination. CT encounters may represent opportunities to improve overall CRC screening rates.

Introduction and aim: Pancreatic cancer is considered one of the most aggressive solid tumors. In Mexico, it is the twelfth cause of cancer, with 4,489 cases diagnosed annually, and accounts for 4.9% of oncologic deaths. Aim: The aim of our study was to describe the clinical and epidemiologic characteristics of the patients diagnosed with pancreatic cancer spanning an 11-year period at the Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”. Methods: A retrospective, cross-sectional study was conducted that included 479 patients diagnosed with pancreatic cancer, within the time frame of 2003-2013. The documented findings were summarized through descriptive statistics. Results: Of the patients with pancreatic ductal adenocarcinoma, 50.9% were women, and the mean patient age at diagnosis was 61.5 years. A total of 48.4% of the cases were diagnosed at clinical stage IV, 12.9% presented with clinical stage III, and 25.0% had localized disease. Surgery was performed on 37.5% of the patients, the most frequent of which was pancreatoduodenectomy. The surgical mortality rate was 5.5%. Conclusion: The clinical characteristics in our study group were similar to those described in the literature. However, the number of candidates for surgical treatment was higher than that reported in other hospitals and the percentage of borderline tumors was lower. Those differences, respectively, are possibly associated with the nature of our referral center and the prolonged intervals between diagnosis and treatment that result in the loss of potential surgical patients. Resumen: Introducción y objetivo: El cáncer de páncreas es considerado uno de los tumores sólidos más agresivos. En México representa la doceava causa de cáncer con 4,489 casos diagnosticados por año y representa el 4.9% de las defunciones oncológicas. El objetivo del estudio es describir las características epidemiológicas y clínicas de los pacientes con diagnóstico de cáncer de páncreas en un periodo de once años del Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”. Métodos: Estudio retrospectivo – transversal que incluyó 479 pacientes con diagnóstico de cáncer de páncreas en el periodo 2003 - 2013. Se incluyó estadística descriptiva para resumir los hallazgos documentados. Resultados: De los pacientes con adenocarcinoma ductal de páncreas el 50.9% fueron mujeres, la edad promedio al diagnóstico fue de 61.5 años. Se diagnosticaron en un estadio clínico IV el 48.4 % de los casos, mientras que el 12.9% se presentaron como estadio clínico III y el 25.0% como enfermedad localizada. El 37.5% de los pacientes fueron sometidos a cirugía, siendo la pancreatoduodenectomía el procedimiento más frecuentemente realizado. La mortalidad quirúrgica fue del 5.5%. Conclusión: Las características clínicas en nuestro grupo de estudio muestran similitud con la literatura, sin embargo, el número de candidatos a un tratamiento quirúrgico fue superior a las cifras reportadas en otros hospitales, no obstante, la cifra de tumores limítrofes fue menor; probablemente asociado con la naturaleza de centro de referencia que representa nuestra institución, así como a la pérdida de pacientes potencialmente quirúrgicos debido a un periodo de ventana prolongado entre diagnóstico y tratamiento.

Drug combinations are being studied as potential therapies to increase the efficacy or improve the safety profile of weight loss medications. This study was designed to determine the anorectic interaction and safety profile of 5-hydroxytryptophan (5-HTP)/carbidopa + diethylpropion and 5-HTP/carbidopa + phentermine combinations in rats. The anorectic effect of individual drugs or in combination was evaluated by the sweetened milk test. Isobologram and interaction index were employed to determine the anorectic interaction between 5-HTP/carbidopa and diethylpropion or phentermine. Plasma serotonin (5-HT) was measured by ELISA. Safety of repeated doses of both combinations in rats was evaluated using the tail sphygmomanometer, cardiac ultrasound, hematic biometry and blood chemistry. A single oral 5-HTP, diethylpropion or phentermine dose increased the anorectic effect, in a dose-dependent fashion, in 12 h-fasted rats. A dose of carbidopa at 30 mg/kg reduced the 5-HTP-induced plasmatic serotonin concentration and augmented the 5-HTP-induced anorectic effect. Isobologram and interaction index indicated a potentiation interaction between 5-HTP/30 mg/kg carbidopa + diethylpropion and 5-HTP/30 mg/kg carbidopa + phentermine. Chronic administration of experimental ED40 of 5-HTP/30 mg/kg carbidopa + phentermine, but not 5-HTP/30 mg/kg carbidopa + diethylpropion, increased the mitral valve leaflets area. Moreover, there were no other significant changes in cardiovascular, hematic or blood parameters. Both combinations induced around 20% body weight loss after 3 months of oral administration. Results suggest that 5-HTP/30 mg/kg carbidopa potentiates the anorectic effect of diethylpropion and phentermine with an acceptable safety profile, but further clinical studies are necessary to establish their therapeutic potential in the obesity treatment.

It is unclear whether patients and providers have started to knowingly request lung cancer screening (LCS) outside US guidelines and insurance coverage for risk factors besides a history of heavy smoking. The authors analyzed their institution's best practices advisory (BPA) clinical decision support system to determine whether providers knowingly order guideline-discordant LCS and the indications given.CT examinations ordered for LCS at an academic medical center that triggered BPA alerts from November 2018 to December 2019 were reviewed. Alerts were triggered by attempts to order examinations outside Medicare coverage, which resembles most US guidelines. Providers can override alerts to order the examinations. Primary outcomes were the number of examinations performed using orders with overridden BPA alerts and indications given. Qualitative exploratory and directed content analyses identified motivators and decision-making processes that drove guideline-discordant screening use.Forty-two patients underwent guideline-discordant LCS, constituting 1.9% of all patients screened (42 of 2,248): 42.9% (18 of 42) were54 or77 years old, 14.3% (6 of 42) had never smoked, 40.5% (17 of 42) had quit15 years earlier, and 31% (13 of 42) had smoked30 pack-years; 45.2% (19 of 42) fell outside all US guidelines. The most common indication was a family history of lung cancer (21.4% [9 of 42]). Perceptions of elevated cancer risk from both patients and referring providers drove guideline-discordant screening use.Referring providers knowingly ordered screening CT examinations outside Medicare coverage and US guidelines, including for never smokers, for indications including a family history of lung cancer. LCS programs may need tailored strategies to guide these patients and providers, such as help with cancer risk assessment.

Background/Context This research is informed by leadership theory and care ethics and how these theories intersect with race-consciousness. This study contributes to the emerging literature on race-conscious leadership ethics that supports building capacity for equity leadership. Purpose The authors explore the intersection of race-consciousness and leadership ethics, studying how leaders explain their practices for increasing equity, their leadership ethics, and their sense of responsibility and personal capacity to address racial achievement disparities. Participants The participants are 22 school leaders: 20 principals and two school district officials from 14 urban and suburban school districts in a metropolitan region in one northeastern state. Research Design This article draws from a semistructured interview study, based on Seidman's three-component interview design but combined in a single interview: history, focus, and reflection. The authors follow a constructivist, exploratory design to develop interpretations and a three-part conceptual framework. Data Collection and Analysis Semistructured interviews allowed the researchers to engage participants in deeper explanations and captured the leaders’ lived experiences through their subjective points of view. Analysis proceeded through a collaborative coding and memo-writing process among the three authors, each contributing distinct historical and racial identities and professional backgrounds. Findings Finding a broad range of perspectives about race and its significance for the experiences of children in school settings, the authors identify variations in moral perspectives that play out in differential views of caring and responsibility, especially when leaders talked about the racial and socioeconomic diversity among their students and how they address inequities in opportunities and outcomes. The authors explore four themes: (a) community-based caring, (b) tough-love/tough-luck caring, (c) color-evasive caring in “fortunate communities,” and (d) caring with minimal responsiveness. Many principals, especially White principals in schools with a small percentage of students of color, maintain a color-evasive perspective and demonstrate “impersonal caring,” with abstract and technical concern for student performance. Race-conscious principals demonstrate caring that takes on different forms, denoted by more marked elaboration of “critical responsibility” for children of color. Between these two perspectives are varied attitudes and perspectives. Conclusions/Recommendations Greater attention is needed for continuing ethical cultivation of school leaders. Across themes, there are multiple routes to developing capacity for race-conscious leadership ethics, through engaging in deeper reflection about personal history, expanding one's understanding of what it means to care across difference, critiquing one's color evasiveness, and learning from colleagues who demonstrate collective responsibility.

Aims. Blood clots play the primary role in neurological deficits after germinal matrix hemorrhage (GMH). Previous studies have shown a beneficial effect in blood clot clearance after hemorrhagic stroke. The purpose of this study is to investigate interleukin-19’s role in hematoma clearance after GMH and its underlying mechanism of IL-20R1/ERK/Nrf2 signaling pathway. Methods. A total of 240 Sprague-Dawley P7 rat pups were used. GMH was induced by intraparenchymal injection of bacterial collagenase. rIL-19 was administered intranasally 1 hour post-GMH. IL-20R1 CRISPR was administered intracerebroventricularly, or Nrf2 antagonist ML385 was administered intraperitoneally 48 hours and 1 hour before GMH induction, respectively. Neurobehavior, Western blot, immunohistochemistry, histology, and hemoglobin assay were used to evaluate treatment regiments in the short- and long-term. Results. Endogenous IL-19, IL-20R1, IL-20R2, and scavenger receptor CD163 were increased after GMH. rIL-19 treatment improved neurological deficits, reduced hematoma volume and hemoglobin content, reduced ventriculomegaly, and attenuated cortical thickness loss. Additionally, treatment increased ERK, Nrf2, and CD163 expression, whereas IL-20R1 CRISPR-knockdown plasmid and ML385 inhibited the effects of rIL-19 on CD163 expression. Conclusion. rIL-19 treatment improved hematoma clearance and attenuated neurological deficits induced by GMH, which was mediated through the upregulation of the IL-20R1/ERK/Nrf2 pathways. rIL-19 treatment may provide a promising therapeutic strategy for the GMH patient population.

Graphical abstract, Highlights • Treatment for moderately ill COVID-19 patients might arise from drug repurposing • RdRp, spike protein, and Mpro are relevant SARS-CoV-2 molecular targets. • Targeting human furin may contain viral infection and inflammation. • Molecular docking and clinical experience is useful for drug repurposing., Several clinical trials to treat Coronavirus 2019 (COVID-19) are in progress around the world. Some of them rely on clinical experience, whereas others include computational predictions. Here, we provide an overview of current efforts in the search for COVID-19 therapies, focusing on structural information of relevant targets. We elaborate on a robust pharmacological rationale for the repurposing of existing drugs, highlighting key advantages of dual therapies with antiviral and anti-inflammatory activity. Furthermore, we provide a consensus list of molecules that could undergo preliminary randomized clinical trials against COVID-19.

Background Disease severity on chest radiographs has been associated with higher risk of disease progression and adverse outcomes from coronavirus disease 2019 (COVID-19). Few studies have evaluated COVID-19-related racial and/or ethnic disparities in radiology. Purpose To evaluate whether non-White minority patients hospitalized with confirmed COVID-19 infection presented with increased severity on admission chest radiographs compared with White or non-Hispanic patients. Materials and Methods This single-institution retrospective cohort study was approved by the institutional review board. Patients hospitalized with confirmed COVID-19 infection between March 17, 2020, and April 10, 2020, were identified by using the electronic medical record (n = 326; mean age, 59 years ±17 [standard deviation]; male-to-female ratio: 188:138). The primary outcome was the severity of lung disease on admission chest radiographs, measured by using the modified Radiographic Assessment of Lung Edema (mRALE) score. The secondary outcome was a composite adverse clinical outcome of intubation, intensive care unit admission, or death. The primary exposure was the racial and/or ethnic category: White or non-Hispanic versus non-White (ie, Hispanic, Black, Asian, or other). Multivariable linear regression analyses were performed to evaluate the association between mRALE scores and race and/or ethnicity. Results Non-White patients had significantly higher mRALE scores (median score, 6.1; 95% confidence interval [CI]: 5.4, 6.7) compared with White or non-Hispanic patients (median score, 4.2; 95% CI: 3.6, 4.9) (unadjusted average difference, 1.8; 95% CI: 0.9, 2.8; P < .01). For both White (adjusted hazard ratio, 1.3; 95% CI: 1.2, 1.4; P < .001) and non-White (adjusted hazard ratio, 1.2; 95% CI: 1.1, 1.3; P < .001) patients, increasing mRALE scores were associated with a higher likelihood of experiencing composite adverse outcome with no evidence of interaction (P = .16). Multivariable linear regression analyses demonstrated that non-White patients presented with higher mRALE scores at admission chest radiography compared with White or non-Hispanic patients (adjusted average difference, 1.6; 95% CI: 0.5, 2.7; P < .01). Adjustment for hypothesized mediators revealed that the association between race and/or ethnicity and mRALE scores was mediated by limited English proficiency (P < .01). Conclusion Non-White patients hospitalized with coronavirus disease 2019 infection were more likely to have a higher severity of disease on admission chest radiographs than White or non-Hispanic patients, and increased severity was associated with worse outcomes for all patients. © RSNA, 2020 Online supplemental material is available for this article.

Background In randomized controlled trials, lung cancer screening with low-dose chest computed tomography (LCS) has been reported to reduce lung cancer mortality. Although initial studies suggested that only approximately 5% of eligible patients have undergone LCS, recent studies have indicated that use of LCS may be increasing nationwide. The objective of the current study was to estimate recent LCS use using cross-sectional survey data from the 2018 Behavioral Risk Factor Surveillance System (BRFSS) survey. Methods The BRFSS is a nationally representative, cross-sectional telephone survey of adults in the United States (response rate of approximately 50%). The 2018 BRFSS survey included questions regarding LCS eligibility and use in 8 states. The primary outcome was the percentage of participants (aged 55-79 years with a smoking history of >30 pack-years) who reported undergoing LCS. Logistic regression analyses evaluated the association between LCS use and sociodemographic characteristics, adjusted for potential confounders and accounting for complex survey design elements. Results A total of 26,910 participants were included, 9.9% of whom were eligible for LCS (95% CI, 8.8%-10.6%). Of the eligible patients, 19.2% reported undergoing LCS (95% CI, 14.0%-24.4%). Approximately 16.4% of current smokers were eligible for LCS (95% CI, 14.2%-18.6%). In our multiple variable analyses of eligible patients, age, sex, marital status, current smoking status, and race were not found to be associated with statistically significant differences in reported LCS (P > .05). Retired patients, patients with personal physicians, and patients who did not complete a high school education were more likely to report receiving LCS (P Conclusions Compared with previously published studies, the results of the current study suggested that LCS use is increasing. However, LCS use remains low (19%) among eligible participants.

Purpose To determine the variability in out-of-pocket costs of lung cancer screening (LCS) for uninsured patients and assess accessibility of this information by telephone or Internet. Methods LCS centers from the ACR’s LCS database were randomly selected. Centers were called between July and August 2019 to determine out-of-pocket cost. Telephone call variables, accessibility of cost information on screening centers’ websites, screening centers’ chargemasters, and publicly available facility and state insurance coverage variables were obtained. Cost information was summarized using descriptive analyses. Multiple variable linear regression analyses were conducted to evaluate effects of facility and state-level characteristics on out-of-pocket costs. Results Fifty-five ACR-accredited LCS centers were included with 78% (43 of 55) willing to provide out-of-pocket cost. Average out-of-pocket cost was $583 ± $607 (mean ± standard deviation), range $49 to $2,409. Average telephone call length 6 ± 3.8 min. Two of fifty-five screening centers’ websites provided out-of-pocket cost information, and one matched cost given over the telephone. A chargemaster was found for 30 of 55 screening centers. No statistically significant differences in out-of-pocket costs were found by geographic region, state percentages of uninsured residents, state percentages of residents with public insurance, or facility safety net hospital affiliation. Discussion Out-of-pocket LCS costs for uninsured patients and availability of this information is highly variable. Radiology practices should be aware of this variability that may influence participation rates among uninsured patients.

Objectives“Assurance behaviors,” a type of defensive medicine, involve physicians’ utilization of additional patient services to avoid adverse legal outcomes. We aim to compare the use of clinical behaviors (such as ordering additional tests, services, and consultations) due to malpractice concerns with the same behaviors due to patient safety concerns.MethodsA national sample of dermatopathologists (n = 160) completed an online survey.ResultsParticipants reported using one or more of five clinical behaviors due to concerns about medical malpractice (95%) and patient safety (99%). Self-reported use of clinical behaviors due to malpractice concerns and patient safety concerns was compared, including ordering additional immunohistochemistry/molecular tests (71% vs 90%, respectively, P < .0001), recommending additional surgical sampling (78% vs 91%, P < .0001), requesting additional slides (81% vs 95%, P < .0001), obtaining second reviews (78% vs 91%, P < .0001), and adding caveats into reports regarding lesion difficulty (85% vs 89%, P > .05).ConclusionsDermatopathologists use many clinical behaviors both as assurance behaviors and due to patient safety concerns, with a higher proportion reporting patient safety concerns as a motivation for specific behaviors.

New findings What is the central question of this study? What is the immediate impact of moderate preterm birth on the structure and function of major conduit arteries using a pre-clinical sheep model? What is the main finding and its importance? Postnatal changes in conduit arteries, including a significant decrease in collagen within the thoracic aortic wall (predominately males), narrowed carotid arteries, reduced aortic systolic blood flow, and upregulation of the mRNA expression of cell adhesion and inflammatory markers at 2 days of age in preterm lambs compared to controls, may increase the risk of cardiovascular impairment in later life. Abstract The aim of this work was to compare the structure and function of the conduit arteries of moderately preterm and term-born lambs and to determine whether vascular injury-associated genes were upregulated. Time-mated ewes were induced to deliver either preterm (132 ± 1 days of gestation; n = 11 females and n = 10 males) or at term (147 ± 1 days of gestation; n = 10 females and n = 5 males). Two days after birth, ultrasound imaging of the proximal ascending aorta, main, right and left pulmonary arteries, and right and left common carotid arteries was conducted in anaesthetized lambs. Lambs were then killed and segments of the thoracic aorta and left common carotid artery were either snap frozen for real-time PCR analyses or immersion-fixed for histological quantification of collagen, smooth muscle and elastin within the medial layer. Overall there were few differences in vascular structure between moderately preterm and term lambs. However, there was a significant decrease in the proportion of collagen within the thoracic aortic wall (predominantly in males), narrowing of the common carotid arteries and a reduction in peak aortic systolic blood flow in preterm lambs. In addition, there was increased mRNA expression of the cell adhesion marker P-selectin in the thoracic aortic wall and the pro-inflammatory marker IL-1β in the left common carotid artery in preterm lambs, suggestive of postnatal vascular injury. Early postnatal differences in the function and structure of conduit arteries and evidence of vascular injury in moderately preterm offspring may place them at greater risk of cardiovascular impairment later in life.

Objective Tobacco use is the leading cause of preventable mortality in the United States. Screening mammography (SM) visits present opportunities for radiology practices to reduce tobacco-related morbidity and mortality. Our study evaluates implementation of a program that provides tobacco cessation service referrals and screens for lung cancer screening (LCS) eligibility among smokers presenting for SM at a community health center. Methods In 2018, two sets of questions were added to our SM patient intake questionnaire to assess (1) smoking history and (2) interest in referral to the health center-based tobacco cessation program for mailed information, telephone-based consultation, and in-person counseling. Primary outcomes were proportion of current smokers who requested a referral and of all smokers who were LCS-eligible. Bivariate logistic regression analyses compared sociodemographic characteristics of smokers who requested versus declined a referral. Results Of the 89.3% (1,907 of 2,136) who responded, 10.5% (201 of 1,907) were current and 29.1% (555 of 1,907) were former smokers. Of current smokers, 26.4% (53 of 201) requested referrals: mailed information by 23.9% (48 of 201), in-person counseling by 9% (18 of 201), and telephone-based consultation by 7.5% (15 of 201). No sociodemographic predictors for referral requests were identified. Of all smokers, 9.3% (70 of 756) were eligible for LCS, of which 31.4% (22 of 70) were up to date. Conclusion One in ten women who underwent SM at our community health center were current smokers, of which one-quarter requested tobacco cessation referrals. Among LCS-eligible smokers, one-third were up to date. SM presents opportunities for radiology practices to advance population health goals such as tobacco cessation and LCS.

Continuous-flow left ventricular assist devices (CF-LVADs) are increasingly used in advanced heart failure patients. Recent studies suggest that low socioeconomic status (SES) predicts worst survival after heart transplantation. Both individual-level and neighborhood-level SES (nSES) have been linked to cardiovascular health; however, the impact of SES in CF-LVAD patients remains unknown. We hypothesized that SES is a major determinant of CF-LVAD candidacy and postimplantation outcomes. A retrospective chart review was conducted on 362 patients between February 2009 and May 2016. Neighborhood-level SES was measured using the American Community Survey data and the Agency for Healthcare Research and Quality SES index score. Individual-level SES was self reported. Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression determined survival statistics. Patients in the highest SES tertile were older (58 ± 13 vs. 53 ± 14; p < 0.001), less likely to be black or Hispanic (26% vs. 70%; p < 0.001), more likely to be married (87% vs. 65%; p < 0.001), more likely to have private insurance (50% vs. 39%; p < 0.001), and more likely to have employment (29% vs. 15%; p < 0.001) compared with patients in the lowest tertile. Low nSES was associated with a decreased risk of death (hazard ratio [HR], 0.580; 95% confidence interval [CI], 0.347-0.970; p = 0.038) in comparison to the high nSES. However, after adjusting for baseline clinical morbidities, the relationship was no longer present. When selecting patients for a LVAD, SES should not be thought of as an immutable risk factor. Carefully selected low-SES patients could be safely implanted with CF-LVAD with outcomes comparable to high-SES patients.

Ketamine has shown promising antidepressant efficacy for adolescent treatment-resistant depression. However, the potential enduring consequences of ketamine exposure have not been thoroughly evaluated. Thus, we examined if juvenile ketamine treatment results in long-lasting changes for the rewarding properties of sucrose and cocaine in adulthood, across three separate experiments. In Experiment 1, adolescent male and female C57BL/6 mice received ketamine (20 mg/kg) for 15 consecutive days (Postnatal Day [PD] 35-49). Twenty-one days later (PD70; adulthood) we examined their behavioral responsivity to sucrose (1%) on a two-bottle choice design, or cocaine (0, 5, 10 mg/kg) using the conditioned place preference (CPP) test. We found that juvenile ketamine-pretreatment increased preference for sucrose and environments paired with cocaine in male, but not female, adult mice. This long-term outcome was not observed when male and female mice received ketamine as adults (PD70-84) and tested for sucrose and cocaine preference 21-days later (Experiment 2). Similarly, in Experiment 3, no long-lasting differences in these measures were observed when adolescent male mice were exposed to concomitant ketamine and social stressors (PD35-44), namely the social defeat or vicarious defeat stress paradigms-procedures that mediated a depression-related phenotype (along with a ketamine antidepressant-like response). Collectively, we demonstrate that in the absence of physical or psychological stress, adolescent ketamine exposure increases later life preference for the rewarding properties of sucrose and cocaine in a sex- and age-specific manner. As such, this preclinical work provides awareness for the potential long-term behavioral consequences associated with juvenile ketamine exposure.

Introduction The attitude toward living liver donation (LLD) among the Spanish population is mostly positive; however, the reality is that liver transplants from live donations are currently minimal. Given this situation, studies that analyze these discrepancies should be carried out. Objective Analyze the attitude toward LLD among family members of patients on the waiting list for liver transplantation. Method Population under study. First-degree relatives of the patients included in the waiting list for liver transplantation. Inclusion criteria. 1. Have the patient's authorization for family members to participate; 2. Accept, the relative, to participate in this investigation; and 3. Be over 18 years old. Opinion survey. The attitude toward LLD is assessed through a questionnaire on psychosocial aspects. Results Patients who accepted family members’ participation in the study were 21 of 112, of which 9 placed restrictions on family access, and 12 authorized family members without restrictions. The participants were 1. children: 52.2% (n = 24); 2. brothers: 30.5% (n = 14); and 3. partners: 17.3% (n = 14). Finally, the authorized relatives and participants in the study were 45. Of these, only 44% (n = 20) would accept to be donors. Conclusions The access to the LLD of the relatives starts from the restriction and initial rejection of the patients themselves on the waiting list. The promotion of LDD is to initially sensitize patients.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be a major global health problem. Lung granulomas are organized structures of host immune cells that function to contain the bacteria. Cytokine expression is a critical component of the protective immune response, but inappropriate cytokine expression can exacerbate TB. Although the importance of proinflammatory cytokines in controlling M. tuberculosis infection has been established, the effects of anti-inflammatory cytokines, such as IL-10, in TB are less well understood. To investigate the role of IL-10, we used an Ab to neutralize IL-10 in cynomolgus macaques during M. tuberculosis infection. Anti–IL-10–treated nonhuman primates had similar overall disease outcomes compared with untreated control nonhuman primates, but there were immunological changes in granulomas and lymph nodes from anti–IL-10–treated animals. There was less thoracic inflammation and increased cytokine production in lung granulomas and lymph nodes from IL-10–neutralized animals at 3–4 wk postinfection compared with control animals. At 8 wk postinfection, lung granulomas from IL-10–neutralized animals had reduced cytokine production but increased fibrosis relative to control animals. Although these immunological changes did not affect the overall disease burden during the first 8 wk of infection, we paired computational modeling to explore late infection dynamics. Our findings support that early changes occurring in the absence of IL-10 may lead to better bacterial control later during infection. These unique datasets provide insight into the contribution of IL-10 to the immunological balance necessary for granulomas to control bacterial burden and disease pathology in M. tuberculosis infection.

OBJECTIVE. The purpose of this article is to assess the "reversed halo" sign in patients with septic pulmonary embolism (PE) due to IV substance use disorder. MATERIALS AND METHODS. A retrospective analysis was performed of chest CT scans obtained between 2007 and 2017 that had findings of septic PE associated with IV substance use disorder. Inclusion criteria were history of IV substance use disorder, findings of septic PE on chest CT scans, and confirmation of infection. Image analysis was performed by three radiologists to assess the frequency, appearance, and evolution of the reversed halo sign. Interreader agreement to characterize the reversed halo sign was assessed using kappa statistical analysis. The chi-square test was used to correlate reversed halo sign shape with evolution on follow-up scans. RESULTS. Of 62 patients who met the inclusion criteria (54.8% women; mean age, 32.8 ± 8.3 [SD] years), 59.7% (37/62) had reversed halo signs (κ = 0.837-0.958, p < 0.0001). The mean number of unique reversed halo signs per patient was 2.1 ± 1.7 (46.7% of patients had more than one reversed halo sign). Of 78 unique reversed halo signs, 93.6% (73/78) were peripherally located and 51.3% (40/78) were located at the lower lobe, 52.6% (41/78) were pyramidal and 47.4% (37/78) were round shaped, 89.7% (70/78) had central low-attenuation areas, and 34.6% (27/78) had internal reticulations. Cavitation developed in 37.2% (29/78) of reversed halo signs and more often in pyramid-shaped ones (70.8%, 17/24), whereas consolidation occurred in 30.8% (24/78) and more often in round-shaped ones (58.6%; 17/29, p = 0.03). CONCLUSION. Septic PE should be considered in the differential diagnosis of patients with IV substance use disorder presenting with reversed halo sign. The reversed halo sign was reliably and frequently observed on the chest CT scans of patients with IV substance use disorder-related septic PE. Characteristics of reversed halo sign presentation were identified as potential features to differentiate septic PE from other causes of pulmonary infarct manifesting with reversed halo sign.

Introduction and objectives To study the incidence, predictors and prognosis of follow-up de novo heart failure (HF) after discharge for acute myocardial infarction (AMI) in patients with left ventricular ejection fraction (LVEF) ≥ 50% and without previous history of HF. Methods Retrospective multicenter registry that includes 2158 consecutive patients discharged for AMI, from January 2011 to December 2015, with LVEF ≥ 50% and without history of HF. The association between clinical variables and the development of de novo HF was assessed by Fine–Gray proportional hazards regression analysis, accounting for death as a competing episode. The adjusted effect of post-discharge HF on subsequent mortality was investigated using extended Cox proportional hazards model. Results During follow-up (20.1 ± 11.8 months), 60 patients (2.8%) had HF admissions, with a cumulative incidence function of 1.7 per 100 patient-year. Age ≥ 70 years, hypertension, atrial fibrillation, and renal dysfunction were independent risk factors for follow-up HF. The HF incidence rate after surviving AMI increased with a higher number of risk factors, from 0.1% in patients with 0, to 1.8%, 3.8%, 15.3%, and 19% in patients with 1, 2, 3, and 4 risk factors, respectively (P Conclusions De novo HF after hospital discharge for ACS in patients with LVEF ≥ 50% is an independent predictor of follow-up death. Fortunately, it is an infrequent post-AMI complication and is easily predictable the combination of 4 clinical risk factors.

Background Adolescent pregnancy carries a high risk of severe health issues for both the mother and the newborn. Worldwide, 21 million adolescents give birth every year, with high percentages in Latin America. Most of the risk factors are met in indigenous communities, which is an underrepresented and poorly studied population. We aimed to assess the determinants of adolescent pregnancy in indigenous communities from the Peruvian central jungle. Methods Through a case–control study, female adolescents aged 13 to 19 years old from seven indigenous communities of the Peruvian central jungle were interviewed. Adolescents with (cases) and with no (controls) pregnancy history, such as current pregnancy, children and abortion, fulfilled our eligible criteria. Our instrument explored: sociodemographic, adolescent and family characteristics, as well as perceptions of adolescent pregnancy. We performed a penalized maximum likelihood logistic regression analysis to obtain Odds Ratios (OR) and their 95% confidence intervals (95% CI). Results We enrolled 34 cases and 107 controls. Overall, 53.9% were 15 to 19 years old. We found a significant association of being 15–19 years old (OR = 6.88, 95% CI 2.38–19.86, p, Plain language summary Worldwide, 21 million adolescents give birth every year, with high percentages in Latin America and rural areas. Indigenous communities are mainly located in rural areas and are exposed to multiple risk factors of adolescent pregnancy. We aimed to find the factors that have an influence on adolescent pregnancy in indigenous communities from the Peruvian central jungle. We conducted a case–control study identifying female indigenous adolescents from the Peruvian central jungle with or without pregnancy history. Our survey explored sociodemographic, adolescent and family characteristics, as well as perceptions of adolescent pregnancy. Being 15 to 19 years old, having an elementary educational level, and five to six siblings increased the risk of adolescent pregnancy. On the other hand, adolescents with sexual and reproductive health communication with parents had a lower risk of adolescent pregnancy. Furthermore, eight out of ten adolescents opposed to sexual intercourse at an early age. Public health and educational efforts should be age-specific focused within indigenous communities of the Peruvian central jungle, encouraging parents to talk about sexual and reproductive health with adolescents. Supplementary Information The online version contains supplementary material available at 10.1186/s12978-021-01247-z.

Background Palpitations are a common complaint among patients seen by primary care physicians (16%). Recent technological advances have led to several novel electrocardiographic monitoring devices. AliveCor Kardia Mobile® (AliveCor, Inc., Mountain View, CA, USA) is a smartphone-based event recorder that allows take an electrocardiogram (ECG) recording during 30 seconds. The usefulness of this device has been studied in atrial fibrillation screening, however, its usefulness in the diagnosis of palpitations is not well known. Objective Evaluate the diagnostic yield of the AliveCor Kardia Mobile® device in unselected patients referred to the cardiologist for the study of palpitations. Methods Uni-centre retrospective study. From September 2018 to October 2020, consecutive patients with palpitations referred to cardiology department were included. After an initial evaluation it was decided monitoring ECG of these patients with this device if they had access to a compatible smartphone. They were instructed to record ECG when they had symptoms. ECG tracings and clinical characteristics were analysed. Results 152 patients were included. Mean age 42±15 years, 68% female. Most of the patients did not have heart disease and about 25% had a history of anxiety-depressive syndrome (Table 1). After monitoring, 31 (20%) patients had rhythm disturbances during symptoms, 82 (54%) patients had no rhythm disturbances related to the symptoms and 39 (26%) patients had no symptoms. Table 2 shows the electrocardiographic findings. Patients with palpitations of arrhythmic origin were older and presented less anxiety/depression (Table 1). Age was the only independent predictor of palpitations of arrhythmic origin (OR, × year: 1.03, 95% CI 1.01–1.06; p=0.035). Conclusions The AliveCor Kardia Mobile® device is easy to use and diagnosed the aetiology of palpitations in a high proportion of patients (74%) referred for specialist evaluation. Funding Acknowledgement Type of funding sources: None.

Despite the success of SARS-CoV-2 vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of COVID-19. Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19, and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct non-overlapping epitopes on the spike protein receptor binding domain to potently neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and abrogate effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry. Together, these two mAbs create a higher barrier to viral escape and a wider breadth of coverage, neutralizing all known SARS-CoV-2 variants of concern. In a non-human primate model of SARS-CoV-2 infection, prophylactic AZD7442 administration prevented infection, while therapeutic administration accelerated virus clearance from lung. In an ongoing Phase I study in healthy participants (NCT04507256), 300 mg intramuscular AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers >10-fold above those of convalescent sera for ≥3 months, which remained 3-fold above those of convalescent sera 9 months post-AZD7442 administration. Approximately 1–2% of serum AZD7442 levels were detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentrations suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19.

Background The goal of this study is to assess the value of point-of-care virtual consultations in radiology. Methods We conducted an institutional review board–approved feasibility study of video-based radiology consultations in an internal medicine primary care clinic at a quaternary academic medical center. The study included 3 primary care providers (PCPs) and enrolled 43 patients. Inclusion criteria consisted of the following: age > 18 years, English speaking, recent radiology examination at our institution, and patient consenting to participate. Patients completed a pre- and postvisit survey. PCPs completed a postvisit survey. Primary study end points included the effect on patient and provider satisfaction, effect on patient experience and understanding of medical condition, and impact on PCP’s management decisions. Statistical significance was assessed using Fisher’s exact test. Results Of the enrolled patients, 93% (n = 40 of 43) indicated that they were satisfied with the virtual consultation visit. The PCPs were satisfied with the virtual consultation in 97% of consultations (n = 42 of 43). In addition, 88% (n = 38 of 43) of patients indicated improved understanding of their medical condition as a result of the virtual consultation, and 91% of patients (n = 39 of 43) were interested in similar consultations in the future. The participating PCPs indicated that the consultation was helpful in their management decisions in 83% of visits. Patient’s interest in receiving their imaging results from radiologist increased from 56% to 88% when comparing pre– and post–virtual consultation survey results (P = .03). Conclusion Initial experience with virtual radiology consultations show high rates of patient and provider satisfaction. Virtual radiology consultations have the potential to advance radiology’s value in care delivery.

Background Germinal matrix hemorrhage (GMH) is defined by the rupture of immature blood vessels in the germinal matrix, where subsequent hemorrhage enters the subependymal zone and the cerebral lateral ventricles. The consequent blood clot has been identified as the causative factor of secondary brain injury, which triggers a series of complex parallel and sequential harmful mechanisms, including neuroinflammation. The orphan G-protein-coupled receptor 40 (GPR40), a free fatty acid (FFA) receptor 1, has been shown to exert anti-inflammatory effects when activated and improved outcomes in animal models of stroke. We aimed to investigate the anti-inflammatory effects of GPR40 and its underlying mechanisms after GMH. Methods GMH model was induced in 7-day-old rat pups by an intraparenchymal injection of bacterial collagenase. GPR40 agonist, GW9508, was administered intranasally 1 h, 25 h, and 49 h after GMH induction. CRISPR targeting GPR40, PAK4, and KDM6B were administered through intracerebroventricular injection 48 h before GMH induction. Neurologic scores, microglia polarization, and brain morphology were evaluated by negative geotaxis, right reflex, rotarod test, foot fault test, Morris water maze, immunofluorescence staining, Western blots, and nissl staining respectfully. Results The results demonstrated that GW9508 improved neurological and morphological outcomes after GMH in the short (24 h, 48 h, 72h) and long-term (days 21–27). However, the neuroprotective effects of treatment were abolished by GW1100, a selective GPR40 antagonist. GW9508 treatment increased populations of M2 microglia and decreased M1 microglia in periventricular areas 24 h after GMH induction. GW9508 upregulated the phosphorylation of PAK4, CREB, and protein level of KDM6B, CD206, IL-10, which was also met with the downregulation of inflammatory markers IL-1β and TNF-α. The mechanism study demonstrated that the knockdown of GPR40, PAK4, and KDM6B reversed the neuroprotective effects brought on by GW9508. This evidence suggests that GPR40/PAK4/CREB/KDM6B signaling pathway in microglia plays a role in the attenuation of neuroinflammation after GMH. Conclusions In conclusion, the present study demonstrates that the activation of GPR40 attenuated GMH-induced neuroinflammation through the activation of the PAK4/CREB/KDM6B signaling pathway, and M2 microglia may be a major mediator of this effect. Thus, GPR40 may serve as a potential target in the reduction of the inflammatory response following GMH, thereby improving neurological outcomes in the short- and long-term.

Ecuadorians are the largest immigrant group in Spain. In countries with preclinical programs of xenotransplantation (XenoTx), it is important to know the population attitude toward them; however, in the Ecuadorian population it is not known.To analyze the attitude toward XenoTx of organs among the Ecuadorian population residing in Spain.Population under study. Ecuadorians residing in Spain.Sample of population over 15 years stratified by age and sex. Instrument valuation. Validated questionnaire of attitude towards xenotransplantation PCID-XenoTx-Ríos. Setting for the study. Random selection of people to survey based on stratification.Of the 461 respondents, 36% are in favor of XenoTx if the results were similar to those obtained with humans, 15% against, and 49% undecided. If the results were worse than with human organs, 11% would be in favor, 26% against, and 63% undecided. The variables associated with this attitude are age (P = .018), marital status (P = .026), studies (P .001), comment with family (P = .001), couple attitude (P = .039), attitude toward cadaveric donation (P .001), previous experience with donation (P = .001), consider the possibility of needing a transplant in the future (P .001), and attitude toward related living donation (P .001). In the multivariate analysis, these data persist: university studies (odds ratio [OR] = 3.875; P = .007); in favor of cadaveric organ donation (OR = 2.840; P .001); previous relationship with donation and organ transplantation (OR = 1.901; P = .026); and consider the possibility of needing a transplant in the future (OR = 4.329; P = .002).The attitude toward XenoTx among Ecuadorian residents in Spain is unfavorable and is conditioned by different psychosocial variables.

Introduction The population of Nicaraguan immigrants is growing in North America; however, they have been little analyzed concerning their attitude toward donation and organ transplantation. Objective To analyze the attitude toward the different types of organ donation among the Nicaraguan population residing in Florida. Methods Study population. Nicaraguan population residing in Florida (USA). Inclusion criteria. Population sample over 15 years stratified by age and sex. Instrument valuation. Attitude questionnaires toward organ donation for transplantation “PCID-DTO-Rios,” “PCID–DVR-Rios,” and “PCID–XenoTx-Rios.” Setting for the study. Random selection of people to be surveyed according to stratification. The assistance of immigrant support associations in Florida was required to locate respondents. Results Sample composed of 89 participants. In the attitude toward donation of one’s own organs after death, 22% (n = 20) were in favor, 41% (n = 36) were against, and 37% (n = 33) were undecided. Regarding the donation of living related organs, 76% were in favor (n = 68), 10% were against (n = 9), and 14% were undecided (n = 12). Finally, regarding attitudes toward the acceptance of organ xenotransplantation, if the results were similar to those obtained with human organs, they were not in favor, with 72% (n = 64) against and 28% (n = 25) doubtful. Conclusions The attitude of the Nicaraguan population residing in Florida toward different types of organ donation is unfavorable.

Objective:Individuals with schizophrenia experience increased lung cancer mortality and decreased access to cancer screening and tobacco cessation treatment. To promote screening among individuals ...

To assess temporal trends and utilization patterns of diagnostic imaging performed for substance use disorder (SUD)-related indications in an academic radiology emergency department (ED).Retrospective analyses of ED imaging examinations acquired from 2005 to 2015 were performed. Imaging examinations performed for suspected SUD-related indications, based on the order history, were compared with those without a SUD-related indication. Unadjusted analyses comparing demographic and imaging characteristics between SUD-related versus non-SUD-related indications used Wilcoxon and Pearson's χAmong 938,245 examinations, 0.17% had an SUD-related indication. Patients with SUD-related indications were younger (mean 37.2 ± 11.1 versus 53.5 ± 22.4, P.001) and more commonly male (65% versus 52%, P.001). The proportions of MR (17%), spine (17%), and extremities (33%) studies performed for SUD-related indications were larger among SUD than non-SUD indications (6%, 8%, 26%, respectively, all P.001). Regression analysis demonstrated the odds of acquiring an ED imaging examination with an SUD-related indication significantly increased over time (P.001, adjusted odds ratio [aOR] = 1.06), which was most pronounced among MR (P.001, aOR = 1.23). For all regression models, younger age, male gender, and body part being imaged were identified as independent predictors of an SUD-related indication for ED imaging.Imaging performed for an SUD-related indication represented a small but increasing subset of overall ED imaging. Utilization of MR for SUD-related indications significantly outpaced growth of MR without SUD-related indications.

Resumen Introduccion y objetivo Nivolumab es un agente inmunoterapeutico aprobado para el tratamiento de pacientes con carcinoma de celulas renales (CCR) avanzado tratados previamente. La experiencia en practica clinica real, especialmente en lo referente a la aparicion de reacciones adversas inmunorrelacionadas, es escasa. Presentamos la experiencia acerca de la seguridad de nivolumab en pacientes con CCR metastasico (CCRm) tratados en 9 hospitales de Espana. Material y metodos Estudio retrospectivo, multicentrico en pacientes con CCRm tratados con nivolumab entre 2016 y 2018. Se recogieron datos sociodemograficos y clinicos basales y las reacciones adversas relacionadas con el farmaco. Resultados Los 26 pacientes incluidos presentaron una edad de 63,7 ± 11,5 anos. El 96% presentaba ECOG 0-1 y el 78% un riesgo MKSCC favorable/intermedio. El 73% presentaba subtipo histologico de celulas claras y el 30%, metastasis de inicio. La mediana de seguimiento fue de 9 meses (rango: 1-14). El 100% de los pacientes presento una reaccion adversa de cualquier grado; las mas frecuentes fueron la fatiga, la fiebre y la anemia (27%). El 23% presento una reaccion adversa de grado 3. Las reacciones adversas llevaron a la suspension del tratamiento en 3 pacientes (11%). Conclusion En la practica clinica real, nivolumab presenta un perfil de seguridad favorable y manejable, similar al descrito en otros estudios.

Introduction and objectives The concurrence of cancer and ischemic heart disease is a controversial issue, given the confluence of risk factors for both diseases. The aim of this study is to analyze the incidence, predictors, and prognosis of new-onset cancer after an acute coronary syndrome (ACS). Methods Retrospective multicenter registry that includes 3867 consecutive patients discharged for ACS without a known history of cancer, from 2011 to 2015. The association between clinical variables and cancer occurrence was assessed by Fine-Gray proportional hazards regression analysis, and its prognostic impact was evaluated using Cox and Fine-Gray regression models. Results The cumulative incidence of cancer was 2.47 per 100 patient/years. Four independent predictors of follow-up cancer were identified: age, male sex, smoking, and human immunodeficiency virus infection. We have constructed a simple risk score, based on the coefficients of these variables in the final multivariable model. Using this score, we stratified our population according to the risk of developing cancer: low (1.03% per year), moderate (2.35% per year), and high-risk (10.51% per year) groups. Post-discharge cancer was independently associated with an increased risk of non-cardiovascular death (HR, 17.65; 95%CI, 10.47–29.76) and bleeding (sHR, 2.54; 95%CI, 1.21–5.34), but not with reinfarction (sHR, 0.50; 95%CI, 0.16–1.56). Conclusions Cancer occurrence after hospital discharge for ACS is relatively low, but it could be predicted by the combination of 4 easily available clinical risk factors: age, male sex, smoking, and human immunodeficiency virus infection. Post-discharge cancer is associated with a higher risk of subsequent death and bleeding events. Resumen Introduccion y objetivos La simultaneidad de cancer y cardiopatia isquemica es un tema controvertido, dada la confluencia de factores de riesgo entre ambas enfermedades. Con este estudio se pretende analizar la incidencia, los factores predictores y el pronostico del cancer de novo tras el alta hospitalaria por sindrome coronario agudo (SCA). Metodos Se trata de un registro multicentrico retrospectivo que incluyo 3.867 pacientes dados de alta tras el SCA y sin historia previa de cancer, de forma consecutiva desde 2011 hasta 2015. La asociacion entre las variables basales y cancer se estudio mediante un analisis de regresion de Fine-Gray, y su impacto pronostico se evaluo mediante modelos de regresion de Cox y de competencia de riesgo (Fine-Gray). Resultados La incidencia acumulada de cancer fue de 2,47 por 100 pacientes/ano. Se identificaron 4 factores de riesgo: edad, sexo masculino, tabaquismo e infeccion por el virus de la inmunodeficiencia humana. De esta forma se construyo una escala de riesgo simplificada basada en los coeficientes de estas variables en el modelo multivariado final. Con esta puntuacion se estratifico nuestra poblacion en funcion del riesgo de desarrollar cancer: riesgo bajo (1,03% por ano), moderado (2,35% por ano) y alto (10,51% por ano). El desarrollo de cancer tras el alta se asocio de forma independiente con un riesgo aumentado de muerte de causa no cardiovascular (HR=17,65; IC95%, 10,47-29,76) y hemorragia (sHR=2,54; IC95%, 1,21-5,34), pero no con reinfarto (sHR=0,50; IC95%, 0,16-1,56). Conclusiones La aparicion de cancer tras el ingreso hospitalario por SCA es relativamente baja, pero se puede predecir a partir de la combinacion de 4 factores de riesgo facilmente disponibles en la practica clinica: edad, sexo masculino, tabaquismo e infeccion por el virus de la inmunodeficiencia humana. El cancer de novo se asocio con mayor riesgo consecuente de muerte no cardiovascular y hemorragia.

Objective This report reflects a meta-analysis that systematically reviewed the literature on intravenous self-administration (IVSA) of nicotine in female and male rats. The goal was to determine if sex differences in nicotine IVSA exist, estimate the magnitude of the effect, and identify potential moderators of the relationship between sex differences and nicotine consumption. Methods Extensive search procedures identified 20 studies that met the inclusion criteria of employing both female and male rats in nicotine IVSA procedures. The meta-analysis was conducted on effect size values that were calculated from mean total intake or nicotine deliveries using the Hedges' unbiased gu statistic. Results A random effects analysis revealed that overall females self-administered more nicotine than males (weighted gu = 0.18, 95% CI [0.003, 0.34]). Subsequent moderator variable analyses revealed that certain procedural conditions influenced the magnitude of sex differences in nicotine IVSA. Specifically, higher reinforcement requirements (> FR1) and extended-access sessions (23 h) were associated with greater nicotine IVSA in females versus males. Females also displayed higher nicotine intake than males when the experiment included a light cue that signaled nicotine delivery. Sex differences were not influenced by the diurnal phase of testing, dose of nicotine, or prior operant training. Conclusion Overall, the results revealed that female rats display higher levels of nicotine IVSA than males, suggesting that the strong reinforcing effects of nicotine promote tobacco use in women.

The goal of this study was to determine the association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) and follow-up heart failure (HF) according to left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction (AMI). This cohort study used a retrospective registry of 8169 consecutive patients discharged with a diagnosis of AMI from two university hospitals in Spain between 2010 and 2016. We used a multivariable competing risk analysis, survival-time inverse probability weighting (IPW) propensity score adjusting, and propensity score matching (PSM) to investigate the association between ACEI/ARB treatment and follow-up HF. During the follow-up (3.3 ± 2.2 years), 1296 patients were admitted for HF (5.2 per 100 person-years). ACEI/ARB use was not associated with fewer follow-up HF admissions in patients with LVEF > 40% (univariate analysis: sub-hazard ratio [sHR] 1.10; 95% confidence interval [CI] 0.95–1.27; p = 0.197; IPW adjusting analysis: sHR 1.11; 95% CI 0.95–1.29; p = 0.192; PSM analysis: sHR 1.12; 95% CI 0.92–1.36; p = 0.248). However, ACEI/ARB use was associated with a significant reduction in HF admission rates in patients with LVEF ≤ 40% (univariate analysis: HR 0.70; 95% CI 0.56–0.88; p = 0.003; IPW adjusting analysis: HR 0.64; 95% CI 0.50–0.83; p = 0.001; PSM analysis: HR 0.65; 95% CI 0.46–0.92; p = 0.014). Among hospitalized survivors of AMI, the use of ACEIs/ARBs was associated with a lower risk of follow-up HF in patients with LVEF ≤ 40% but not in those with LVEF > 40%. Further prospective studies are needed to confirm our results.

Red cell distribution width (RDW) measures the variance in size of circulating red blood cells and is a strong independent predictor of morbidity and mortality in cardiovascular disease and heart failure. Predictive power of RDW on mortality after continuous-flow left ventricular assist device (CF-LVAD) implantation remains largely unknown. Four hundred nine patients who underwent CF-LVAD implantation between April 2004 and December 2015 were retrospectively analyzed. The primary outcome of interest was 90 day mortality after CF-LVAD implantation. Median RDW before CF-LVAD implantation was 15.8%. Patients with elevated RDW (>15.8%) at baseline had significantly lower hemoglobin (10.6 ± 1.8 vs. 11.9 ± 2.1 mg/dl; p < 0.001), lower mean corpuscular volume (84.9 ± 7.7. vs. 88.7 ± 5.9; p < 0.001), higher blood urea nitrogen (BUN; 36.3 ± 21.8 vs. 30.1 ± 17.1; p < 0.001), lower albumin (3.4 ± 0.6 vs. 3.7 ± 0.5; p < 0.001), and higher total bilirubin levels (1.67 ± 2.21 vs. 1.29 ± 0.96). Red cell distribution width was independently predictive of 90 day mortality (odds ratio [OR], 1.16 for 1% increase; CI, 1.04-1.31; p = 0.010). Discriminatory power of RDW alone was comparable to model of end-stage liver disease excluding international normalized ratio (MELD-Xi) and HeartMate II risk scores. Mechanical unloading with CF-LVAD was associated with a reduction in RDW levels. These findings suggest that RDW, a simple and inexpensive test available through routine complete blood count, can be successfully used for mortality risk assessment in CF-LVAD candidates.