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Background: Patients with small cell lung cancer (SCLC) have historically been characterised by poor overall survival (OS) and high risk for brain metastasis (BM), but large-scale real-world evidence on clinical presentation and treatment in this population is lacking. Our aim was to describe the clinical characteristics and outcomes of patients with SCLC and BM in Ontario, Canada. Methods: This population-based, retrospective cohort study included all patients in Ontario, Canada, who were diagnosed with SCLC between April 1, 2010, and March 31, 2018. Data were analysed between June 2, 2022, and December 20, 2023. Patients with second cancer diagnosis were excluded. Patients were identified and data retrieved from the Institute for Clinical Evaluative Sciences (ICES) databases. Kaplan-Meier and multivariable Cox regression analyses were performed to compare OS between patient cohorts stratified by disease stage, BM diagnosis, and intracranial treatment modality. Propensity score-matching based on age, disease stage, time to BM, and receipt of chemotherapy was performed to compare OS between intracranial treatment modalities. Findings: 8705 patients were included (male: 4433, female: 4272). Median age at diagnosis was 68 years (interquartile range, IQR, 61-75). Median OS of all patients was 7.46 months (95% confidence interval, CI, 7.23-7.69). 32% (n = 2686) of patients developed BM (synchronous, 43.7%; asynchronous, 56.3%) with median OS of 9.76 months (95% CI, 9.36-10.22). 102 (4%), 1654 (62%), and 930 (35%) patients received stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), or no treatment, respectively, for their BM in the first-line setting or after prophylactic cranial irradiation (PCI). In propensity score-matched analyses, OS from time of BM diagnosis was non-inferior between SRS- and WBRT-treated cohorts among patients who did not receive PCI (hazard ratio, HR, 0.68, 95% CI, 0.44-1.06, p = 0.091, n = 86) and in favour of SRS for those who received PCI prior to BM development (HR, 0.47, 95% CI, 0.31-0.72, p = 0.0042, n = 112). Interpretation: OS for patients with SCLC remains poor, and many patients present with BM. With careful selection, patients with SCLC and BM may benefit from SRS treatment. Future research should incorporate information on burden of intracranial disease and novel immunotherapies. Funding: None.
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BACKGROUND: We aimed to determine the effect of aortic annular enlargement on the midterm outcomes of aortic valve replacement surgery by comparing patients with the same-sized (≤23 mm) native aortic annuli. METHODS: From January 2011 to June 2022, 1328 patients underwent isolated aortic valve replacement-1163 without aortic annular enlargement (AVR group) and 165 with aortic annular enlargement (AVR+AAE group). Propensity score matching identified 112 pairs, controlling for native aortic annulus diameter, age, sex, diabetes, chronic lung disease, dialysis, ejection fraction, prior cardiac surgery, indication, hypertension, dyslipidemia, valve type, prior stroke, prior myocardial infarction, and case status. RESULTS: Demographic and preoperative variables were similar, except body surface area was larger in the AVR+AAE group (2.1 m2 vs 1.9 m2). Median native aortic annulus diameter was 23 mm in both groups. Median prosthesis size was 25 in the AVR+AAE group and 23 in the AVR group. The AVR+AAE group had longer cardiopulmonary bypass (143 vs 111 minutes) and cross-clamp (115 vs 82 minutes) times. Incidences of perioperative complications, including operative mortality (1.8% AVR+AAE vs 3.6% AVR) were similar between groups. Survival at 6 years was 98% in the AVR+AAE group and 74% in the AVR group (P = .016). Aortic annular enlargement was an independent protective factor for midterm mortality, with a hazard ratio of 0.19 (P = .006). The rate of moderate/severe patient-prosthesis mismatch was 19% in the AVR+AAE group and 31% in the AVR group (P = .16). CONCLUSIONS: Patients with small native aortic annuli (≤23 mm) undergoing isolated aortic valve replacement may benefit from aortic annular enlargement.
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Allergy to galactose-α-1,3-galactose (alpha-gal) is associated with immediate allergic manifestations and premature degeneration of the prosthesis in patients who receive bovine- or porcine-derived bioprosthetic valves. Here, we report a 72-year-old man with atrial fibrillation, aortic regurgitation, and severe alpha-gal allergy who presented for consideration of aortic valve replacement. He was premedicated with antihistamines and steroids and underwent aortic valve replacement with 25-mm INSPIRIS aortic valve (Edwards Lifesciences) and left atrial appendage occlusion with 40-mm AtriClip device (AtriCure), without immediate or short-term complications.
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Válvula Aórtica , Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Humanos , Anciano , Bioprótesis/efectos adversos , Masculino , Prótesis Valvulares Cardíacas/efectos adversos , Animales , Bovinos , Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Disacáridos , Hipersensibilidad/etiología , Insuficiencia de la Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/etiologíaRESUMEN
OBJECTIVES: The Emergency Department Work Index (EDWIN) is a validated overcrowding score shown to correlate well with staff assessment of adult emergency department (ED) overcrowding and the potential need for diversion. It derives from the number of staffed ED beds, attending physicians on duty, patients within each triage category, and admitted patients. To date, no study has validated EDWIN in a pediatric community ED setting. We aim to determine if EDWIN correlates with established overcrowding measures and provider perception of overcrowding within a freestanding, community-based pediatric ED. METHODS: In this prospective observational study at a freestanding, community-based pediatric ED, EDWIN was calculated hourly over 8 weeks throughout the year. EDWIN was compared with other objective and previously established ED metrics of overcrowding, including rates of patients who left without being seen (LWBS), average time from arrival to ED room, average length of stay (LOS), ED occupancy rates, and number of patients in the waiting room. Furthermore, EDWIN was compared with provider perception of overcrowding by surveying providers 6 times a day during the study period using novel, real-time, longitudinal, electronic health record-based survey distribution methodology. Spearman correlation coefficients were calculated to characterize the associations between EDWIN vs provider perception and EDWIN vs ED metrics. ANOVA and Tukey HSD were used to compare means of ED metrics of overcrowding across EDWIN severity categories. RESULTS: Five hundred eleven provider perception survey responses were collected from July 2022 through January 2023. EDWIN directly correlated with all measures of overcrowding, including provider perception of crowdedness (rho = 0.67), LWBS rates (rho = 0.44), average time from arrival to ED room (rho = 0.74), average LOS (rho = 0.70), ED occupancy rates (rho = 0.68), and number of patients in the waiting room (rho = 0.65). All findings were statistically significant (P < 0.05). CONCLUSIONS: Our findings suggest that EDWIN is an accurate tool to measure overcrowding in a freestanding, community-based pediatric ED.
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Bacteria in the genus Staphylococcus are pathogenic and harmful to humans. Alarmingly, some Staphylococcus, such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) have spread worldwide and become notoriously resistant to antibiotics, threatening and concerning public health. Hence, the development of new Staphylococcus-targeting diagnostic and therapeutic agents is urgent. Here, we chose the S. aureus-secreted siderophore staphyloferrin A (SA) as a guiding unit. We developed a series of Staphyloferrin A conjugates (SA conjugates) and showed the specific targeting ability to Staphylococcus bacteria. Furthermore, among the structural factors we evaluated, the stereo-chemistry of the amino acid backbone of SA conjugates is essential to efficiently target Staphylococci. Finally, we demonstrated that fluorescent Staphyloferrin A probes (SA-FL probes) could specifically target Staphylococci in complex bacterial mixtures.
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This retrospective study uses electronic health record data to investigate the sex differences in guideline-based management outcomes between male and female patients with chronic kidney disease.
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Disparidades en Atención de Salud , Atención Primaria de Salud , Insuficiencia Renal Crónica , Anciano , Femenino , Humanos , Masculino , Manejo de la Enfermedad , Atención Primaria de Salud/normas , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/terapia , Factores Sexuales , Estados Unidos , Cistatina C/sangre , Guías de Práctica Clínica como Asunto , Anciano de 80 o más Años , Disparidades en Atención de Salud/normasRESUMEN
The dead donor rule (DDR) has facilitated the saving of hundreds of thousands of lives. Recent advances in heart donation, however, have exposed how DDR has limited donation of all organs. We propose advancing the moment in the dying process at which death can be determined to increase substantially the supply of organs for transplantation. We justify this approach by identifying certain flaws in the Uniform Determination of Death Act and proposing a modification of that law that permits earlier procurement of healthier organs in greater numbers.
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Muerte , Donantes de Tejidos , Obtención de Tejidos y Órganos , Humanos , Obtención de Tejidos y Órganos/ética , Obtención de Tejidos y Órganos/legislación & jurisprudencia , Donantes de Tejidos/provisión & distribución , Estados Unidos , Muerte EncefálicaRESUMEN
AIM: The aim of the third Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2023) was to discuss the application in the Asia-Pacific (APAC) region of consensus statements from the 4th Advanced Prostate Cancer Consensus Conference (APCCC 2022). METHODS: The one-day meeting in July 2023 brought together 27 experts from 14 APAC countries. The meeting covered five topics: (1) Intermediate- and high-risk and locally advanced prostate cancer; (2) Management of newly diagnosed metastatic hormone-sensitive prostate cancer; (3) Management of non-metastatic castration-resistant prostate cancer; (4) Homologous recombination repair mutation testing; (5) Management of metastatic castration-resistant prostate cancer. Pre- and post-symposium polling gathered APAC-specific responses to APCCC consensus questions and insights on current practices and challenges in the APAC region. RESULTS: APAC APCCC highlights APAC-specific considerations in an evolving landscape of diagnostic technologies and treatment innovations for advanced prostate cancer. While new technologies are available in the region, cost and reimbursement continue to influence practice significantly. Individual patient considerations, including the impact of chemophobia on Asian patients, also influence decision-making. CONCLUSION: The use of next-generation imaging, genetic testing, and new treatment combinations is increasing the complexity and duration of prostate cancer management. Familiarity with new diagnostic and treatment options is growing in the APAC region. Insights highlight the continued importance of a multidisciplinary approach that includes nuclear medicine, genetic counseling, and quality-of-life expertise. The APAC APCCC meeting provides an important opportunity to share practice and identify APAC-specific issues and considerations in areas of low evidence where clinical experience is growing.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/patología , Asia/epidemiología , Neoplasias de la Próstata Resistentes a la Castración/terapia , Neoplasias de la Próstata Resistentes a la Castración/patologíaRESUMEN
Importance: Chronic kidney disease (CKD) affects 37 million adults in the United States, and for patients with CKD, hypertension is a key risk factor for adverse outcomes, such as kidney failure, cardiovascular events, and death. Objective: To evaluate a computerized clinical decision support (CDS) system for the management of uncontrolled hypertension in patients with CKD. Design, Setting, and Participants: This multiclinic, randomized clinical trial randomized primary care practitioners (PCPs) at a primary care network, including 15 hospital-based, ambulatory, and community health center-based clinics, through a stratified, matched-pair randomization approach February 2021 to February 2022. All adult patients with a visit to a PCP in the last 2 years were eligible and those with evidence of CKD and hypertension were included. Intervention: The intervention consisted of a CDS system based on behavioral economic principles and human-centered design methods that delivered tailored, evidence-based recommendations, including initiation or titration of renin-angiotensin-aldosterone system inhibitors. The patients in the control group received usual care from PCPs with the CDS system operating in silent mode. Main Outcomes and Measures: The primary outcome was the change in mean systolic blood pressure (SBP) between baseline and 180 days compared between groups. The primary analysis was a repeated measures linear mixed model, using SBP at baseline, 90 days, and 180 days in an intention-to-treat repeated measures model to account for missing data. Secondary outcomes included blood pressure (BP) control and outcomes such as percentage of patients who received an action that aligned with the CDS recommendations. Results: The study included 174 PCPs and 2026 patients (mean [SD] age, 75.3 [0.3] years; 1223 [60.4%] female; mean [SD] SBP at baseline, 154.0 [14.3] mm Hg), with 87 PCPs and 1029 patients randomized to the intervention and 87 PCPs and 997 patients randomized to usual care. Overall, 1714 patients (84.6%) were treated for hypertension at baseline. There were 1623 patients (80.1%) with an SBP measurement at 180 days. From the linear mixed model, there was a statistically significant difference in mean SBP change in the intervention group compared with the usual care group (change, -14.6 [95% CI, -13.1 to -16.0] mm Hg vs -11.7 [-10.2 to -13.1] mm Hg; P = .005). There was no difference in the percentage of patients who achieved BP control in the intervention group compared with the control group (50.4% [95% CI, 46.5% to 54.3%] vs 47.1% [95% CI, 43.3% to 51.0%]). More patients received an action aligned with the CDS recommendations in the intervention group than in the usual care group (49.9% [95% CI, 45.1% to 54.8%] vs 34.6% [95% CI, 29.8% to 39.4%]; P < .001). Conclusions and Relevance: These findings suggest that implementing this computerized CDS system could lead to improved management of uncontrolled hypertension and potentially improved clinical outcomes at the population level for patients with CKD. Trial Registration: ClinicalTrials.gov Identifier: NCT03679247.
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Antihipertensivos , Sistemas de Apoyo a Decisiones Clínicas , Hipertensión , Insuficiencia Renal Crónica , Humanos , Femenino , Masculino , Hipertensión/tratamiento farmacológico , Hipertensión/complicaciones , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Antihipertensivos/uso terapéutico , Anciano , Persona de Mediana Edad , Atención Primaria de Salud/métodosRESUMEN
Obesity results from excessive caloric input associated with overeating and presents a major public health challenge. The hypothalamus has received significant attention for its role in governing feeding behavior and body weight homeostasis. However, extrahypothalamic brain circuits also regulate appetite and consumption by altering sensory perception, motivation, and reward. We recently discovered a population of basal forebrain cholinergic (BFc) neurons that regulate appetite suppression. Through viral tracing methods in the mouse model, we found that BFc neurons densely innervate the basolateral amygdala (BLA), a limbic structure involved in motivated behaviors. Using channelrhodopsin-assisted circuit mapping, we identified cholinergic responses in BLA neurons following BFc circuit manipulations. Furthermore, in vivo acetylcholine sensor and genetically encoded calcium indicator imaging within the BLA (using GACh3 and GCaMP, respectively) revealed selective response patterns of activity during feeding. Finally, through optogenetic manipulations in vivo, we found that increased cholinergic signaling from the BFc to the BLA suppresses appetite and food intake. Together, these data support a model in which cholinergic signaling from the BFc to the BLA directly influences appetite and feeding behavior.
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Prosencéfalo Basal , Complejo Nuclear Basolateral , Ratones , Animales , Complejo Nuclear Basolateral/fisiología , Prosencéfalo Basal/fisiología , Neuronas Colinérgicas/fisiología , Colinérgicos , Ingestión de Alimentos/fisiologíaRESUMEN
INTRODUCTION: The goal of this study was to evaluate the relationship between hospital-related factors and hospital type on outcomes of heart transplantation for patients with adult congenital heart disease (ACHD). METHODS: Patients with ACHD who underwent heart transplant between 2010 and 2021 were identified using the United Network for Organ Sharing data registry. The primary outcome was post-transplant mortality. Kaplan-Meier unadjusted survival curves were compared using the log-rank test. Multivariable Cox proportional hazard models were used for risk-adjustment in evaluating the independent effect of hospital type on post-transplant mortality. RESULTS: Of 70 centers, 54 (77.1%) adult centers performed 415 (87.0%) heart transplants and 16 (22.9%) pediatric centers performed 62 (13.0%) heart transplants. Patients transplanted at pediatric centers were younger, had lower creatinine levels, and had lower body mass index. The unadjusted 1-y and 5-y survival was comparable in pediatric versus adult centers, respectively: 93.4% versus 86.6% (log-rank P = 0.16) and 87.4% versus 73.9% (log-rank P = 0.06). These findings persisted after risk-adjustment. One-year mortality hazard ratio for pediatric hospitals: 0.64 (0.22-1.89, P = 0.416) and 5-y mortality hazard ratio for pediatric hospitals: 0.53 (0.21-1.33, P = 0.175). Rates of acute rejection, postoperative stroke, and new-onset postoperative dialysis were also comparable. CONCLUSIONS: Heart transplantation for patients with ACHD can be performed safely in adult centers. The majority of heart transplant for ACHD in the United States are performed at adult hospitals. However, further research is needed to delineate the impact of individual surgeon characteristics and hospital-related factors on outcomes.
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Cardiopatías Congénitas , Trasplante de Corazón , Humanos , Adulto , Niño , Estados Unidos/epidemiología , Hospitales Pediátricos , Cardiopatías Congénitas/cirugía , Modelos de Riesgos Proporcionales , Estimación de Kaplan-Meier , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Axonal degeneration is a key component of neurodegenerative diseases such as Huntington's disease (HD), Alzheimer's disease, and amyotrophic lateral sclerosis. Nicotinamide, an NAD+ precursor, has long since been implicated in axonal protection and reduction of degeneration. However, studies on nicotinamide (NAm) supplementation in humans indicate that NAm has no protective effect. Sterile alpha and toll/interleukin receptor motif-containing protein 1 (SARM1) regulates several cell responses to axonal damage and has been implicated in promoting neuronal degeneration. SARM1 inhibition seems to result in protection from neuronal degeneration while hydrogen peroxide has been implicated in oxidative stress and axonal degeneration. The effects of laser-induced axonal damage in wild-type and HD dorsal root ganglion cells treated with NAm, hydrogen peroxide (H2O2), and SARM1 inhibitor DSRM-3716 were investigated and the cell body width, axon width, axonal strength, and axon shrinkage post laser-induced injury were measured.
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Enfermedad de Huntington , Peróxido de Hidrógeno , Animales , Ratones , Humanos , Niacinamida , Ratones Noqueados , Neuronas/metabolismo , Proteínas del Citoesqueleto/metabolismo , Proteínas del Dominio Armadillo/genética , Proteínas del Dominio Armadillo/metabolismoRESUMEN
INTRODUCTION AND OBJECTIVES: Compared to premenopausal women, postmenopausal women are at greater risk of developing NAFLD and NASH, two common indications for liver transplantation (LT). We aim to determine the prevalence of NASH-related cirrhosis in postmenopausal women from a cohort of LT patients and investigate their post-LT complications. MATERIALS AND METHODS: Chart review of 1200 LT patients from 2002-2020 was performed. Postmenopausal women were defined as women over 51 and compared to a control group of men over 51. Prevalence of LT indications was determined. Subgroup analysis assessed cardiovascular disease risk. BMI and ASCVD risk scores were calculated at the time of LT and after 1 year. RESULTS: 510 patients met the inclusion criteria: 189 (37.1%) women and 321 (62.9%) men. The most common indication was NASH for women (26.5%, p<0.001) and alcohol-related cirrhosis for men (23.1%). 53 men and 46 women underwent subgroup analysis. There was no significant difference in BMI or ASCVD 10-year risk post-LT between sexes. MI occurred more in men (n=9.17%) than women (n=1, 2%, p=0.015), with no significant differences in CAD, CHF, or stroke. LT complications occurred less in men (n=5.9%) than women (n=20, 43%, p=0.0001). CONCLUSIONS: Postmenopausal women were significantly more likely to have NASH as an indication for LT than men. Postmenopausal women had greater weight gain and more noncardiac complications than men. Women did not have increased cardiovascular outcomes, ASCVD risk, or mortality. Diet education and weight control in postmenopausal women with existing risk factors for NASH should be encouraged to modulate health outcomes.
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Trasplante de Hígado , Enfermedad del Hígado Graso no Alcohólico , Masculino , Humanos , Femenino , Trasplante de Hígado/efectos adversos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Prevalencia , Posmenopausia , Estudios Retrospectivos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Factores de Riesgo , Cirrosis Hepática Alcohólica/complicacionesRESUMEN
BACKGROUND: Coronary artery aneurysms (CAAs), coronary arteriovenous malformations (CAVMs), and spontaneous coronary artery dissections (SCADs) are rare clinical entities, and much is unknown about their natural history, prognosis, and management. METHODS: A systematic search of MEDLINE, Embase, and Cochrane Library databases was performed in March 2023 to identify published papers related to CAAs, CAVMs, and SCADs. RESULTS: CAAs are found in 0.3% to 12% of patients undergoing angiography and are often associated with coronary atherosclerosis. They are usually asymptomatic but can be complicated by thrombosis in up to 4.8% of patients and rarely by rupture (0.2%). CAAs can be managed medically, percutaneously with stents or coil embolization, and surgically. The most common surgical procedure is ligation of the aneurysm, followed by coronary artery bypass grafting. The incidence of CAVMs is 0.1% to 0.2% in patients undergoing angiography, and they are most likely associated with congenital abnormal development of the coronary vessels. The diagnosis of CAVMs is usually incidental. Surgical or percutaneous intervention is indicated for patients with large CAVMs, which carry a potential risk of myocardial infarction. SCADs represent 1% to 4% of all acute coronary syndromes and typically affect young women. SCADs are strongly correlated with pregnancy, suggesting the role of sex hormones in their pathogenesis. Conservative management of SCAD is preferred for stable patients without signs of ischemia as spontaneous resolution is frequently reported. Unstable patients should undergo revascularization either percutaneously or with coronary artery bypass grafting. CONCLUSIONS: Further evidence regarding the management of these rare diseases is needed and can ideally be derived from multicenter collaborations.
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BACKGROUND: Kidney biopsies are procedures commonly performed in clinical nephrology and are increasingly used in research. In this study we aimed to evaluate the experiences of participants who underwent research kidney biopsies in the Kidney Precision Medicine Project (KPMP). METHODS: KPMP research participants with acute kidney injury (AKI) or chronic kidney disease (CKD) were enrolled at nine recruitment sites in the United States between September 2019 to January 2023. At 28 days post-biopsy, participants were invited to complete a survey to share their experiences, including: motivation to participate in research; comprehension of informed consent; pain and anxiety during and after the biopsy procedure; overall satisfaction with KPMP participation; and impact of the study on their lives. The survey was developed in collaboration with the KPMP Community Engagement Committee and the Institute of Translational Health Sciences at the University of Washington. RESULTS: 111 participants completed the survey, 23 enrolled for AKI and 88 for CKD. Median age was 61 (IQR 48-67) years, 43% were women, 28% were Black, and 18% were of Hispanic ethnicity. Survey respondents most commonly joined KPMP to help future patients (59%). The consent form was understood by 99% and 97% recognized their important role in the study. Pain during the biopsy was reported by 50%, at a median level of 1 (IQR 0-3) on a 0-10 scale. Anxiety during the biopsy was described by 64% at a median level of 3 (IQR 1-5) on a 0-10 scale. More than half conveyed that KPMP participation impacted their diet, physical activity, and how they think about kidney disease. CONCLUSIONS: KPMP survey respondents were most commonly motivated to participate in research protocol kidney biopsies by altruism, with excellent understanding of the informed consent process.
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BACKGROUND: JC polyomavirus(JCPyV) causes progressive multifocal leukoencephalopathy(PML), a potentially fatal complication of severe immune suppression with no effective treatment. Natural killer (NK) cells play critical roles in defense against viral infections, yet NK cell response to JCPyV infection remains unexplored. METHODS: NK and T cell responses against the JCPyV VP1 were compared using intracellular cytokine staining (ICS) upon stimulation with peptide pools. A novel flow cytometry-based assay was developed to determine NK cell killing efficiency of JCPyV-infected astrocyte-derived SVG-A cells. Blocking antibodies were used to identify the specific NK cell receptors in immune recognition of JCPyV-infected cells. RESULTS: In about 40% of healthy donors, we detected robust CD107a upregulation and IFN-γ production by NK cells, extending beyond T cell responses. Next, using the NK cell-mediated killing assay, we showed that co-culture of NK cells and JCPyV-infected SVG-A cells leads to a 60% reduction in infection, on average. JCPyV-infected cells had enhanced expression of ULBP2 - a ligand for the activating NK cell receptor NKG2D and addition of NKG2D blocking antibodies decreased NK cell degranulation. CONCLUSION: NKG2D-mediated activation of NK cells plays a key role in controlling JCPyV replication and may be a promising immunotherapeutic target to boost NK cell anti-JCPyV activity.
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Headache is a common complaint in pediatric patients presenting to the emergency department. Diagnosis of life-threatening pathology can be difficult due to the nonspecific symptoms for many of these conditions. Emergency clinicians must have a high index of suspicion, obtain a detailed history, and conduct a thorough physical examination to accurately identify life-threatening causes of headache. This issue reviews the general approach, differential diagnosis, and initial workup and management of the most common dangerous causes of secondary headaches in pediatric patients.
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Servicio de Urgencia en Hospital , Cefalea , Humanos , Niño , Cefalea/diagnóstico , Cefalea/etiología , Cefalea/terapia , Examen Físico , Diagnóstico DiferencialRESUMEN
Introduction: The ability to produce a well-structured, coherent and informative narrative requires the integration of lexical and grammatical skills at different levels of complexity. Investigating how narrative macrostructure competence is predicted by microstructural linguistic skills is conceptually enlightening; yet there have been very few, if any, studies documenting the associations between macrostructure and microstructure in both languages of the same bilinguals. In this paper we attempt to address this research gap and report on the first empirical study of Urdu-Cantonese bilingual children's narrative abilities, bringing in data from a new language pair that is currently understudied. Methods: Twenty-four bilinguals (mean age = 9.17 years) acquiring Urdu as first, family and heritage minority language, and Cantonese as second, school and majority language were assessed via Multilingual Assessment Instrument for Narratives (MAIN). We examined these children's macrostructural competence and its relations to microstructural skills in both languages (Urdu and Cantonese). Three macrostructure components were scored as response variables: Story Structure (SS), Story Complexity (SC), Internal State Terms (IST). Four microstructural measures were scored as predictor variables: number of different words (NDW), mean length of Communication Units (MLCU), proportion of grammatical Communication Units (Gproportion), proportion of correct connectives linking the major episodic elements (Cproportion). Results: In regression analyses, NDW emerged consistently as a positive predictor of SS, SC and IST in both languages. MLCU and NDW were positive predictors of SS in the stronger L1, but NDW was the only positive predictor of SS in L2. By contrast, NDW and an index of syntactic competence (MLCU in L1, but Cproportion in L2) were significant or close-to-significant positive predictors of SC in both languages. NDW was the only positive predictor of IST in both languages. These findings suggested that the relationships between narrative macrostructure and specific microstructural abilities could manifest both similarly and differently between L1 and L2. Discussion: We discuss the findings by considering the unique nature of each macrostructure component and how each component might be related to specific microstructural linguistic skills. We suggest directions for further research and discuss how the current findings bring deeper implications for educators and clinicians in assessment, pedagogy, and intervention.
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INTRODUCTION: Systemic racism impacts personal and community health; however, education regarding its role in perpetuating healthcare inequity remains limited in medical curricula. This study implemented and evaluated the impact of a student-led anti-racism programme on medical students' perceptions of racial bias in medicine, awareness of, and confidence to advocate against racism in medicine. METHOD: A total of 543 early stage medical students were invited to participate in the programme. Participants were assigned readings and videos exploring racial injustice in medicine and attended a virtual small-group discussion facilitated by faculty and students. Online surveys were used to collect pre- and post-programme data using Likert scales for response items. Open-ended questions were independently reviewed by three authors using reflexive thematic analysis. RESULTS: Sixty-three early-stage medical students enrolled in the programme, of which 42 completed the pre-programme survey. There was a 76% (n = 32) response rate for the post-programme survey. The majority of students (60%, n = 25) had no previous education about racism in medicine. From pre- to post-programme, there was a significant change in students' perceived definition of race from genetic, biological, geographical, and cultural factors to socio-political factors (P < 0.0001). Significant increases in almost all factors assessing student awareness of racism and confidence to advocate against racism were observed. Student-identified barriers to discussing racism included lack of education and lived experience, fear of starting conflict and offending others. All survey respondents would recommend this programme to peers and 69% (n = 32) engaged in further topical self-directed education. CONCLUSION: This simple and reproducible programme improved awareness and confidence to advocate against racism in medicine and resulted in a change in opinion regarding race-based medical practice. These findings are in line with best practice towards addressing racial bias in medicine, decolonizing medical curricula and strengthening anti-racism teaching of future physicians.