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PURPOSE: The purpose of this study was to assess the association of comorbidity burden with overall survival, accounting for racial/ethnic and socioeconomic differences in patients with cancer. METHODS: In this retrospective cohort study, patients newly diagnosed with cancer between 2010 and 2018 were identified from a large health plan in southern California. Cancer registry data were linked with electronic health records (EHR). Comorbidity burden was defined by the Elixhauser comorbidity index (ECI). Patients were followed through December 2019 to assess all-cause mortality. Association of comorbidity burden with all-cause mortality was evaluated using Cox proportional hazards model. Crude and adjusted hazard ratio (HR, 95%CI) were determined. RESULTS: Of 153,270 patients included in the analysis, 29% died during the ensuing 10-year follow-up. Nearly 49% were patients of color, and 32% had an ECI > 4. After adjusting for age, sex, race/ethnicity, cancer stage, smoking status, insurance payor, medical center, year of cancer diagnosis, and cancer treatments, we observed a trend demonstrating higher mortality risk by decreasing socioeconomic status (SES) (P-trend<.05). Compared to patients in the highest SES quintile, patients in the lowest, second lowest, middle, and second highest quintiles had 25%, 21%, 18%, and 11% higher risk of mortality, respectively [(HR, 95%CI): 1.25 (1.21-1.29), 1.21 (1.18-1.25), 1.18 (1.15-1.22), and 1.11 (1.07-1.14), respectively]. When we additionally adjusted for ECI, the adjusted HRs for SES were slightly attenuated; however, the trend persisted. Patients with higher comorbidity burden had higher mortality risk compared to patients with ECI score = 0 in the adjusted model [(HR, 95%CI): 1.22 (1.17-1.28), 1.48 (1.42-1.55), 1.80 (1.72-1.89), 2.24 (2.14-2.34), and 3.39 (3.25-3.53) for ECI = 1, 2, 3, 4, and >5, respectively]. CONCLUSIONS: Comorbidity burden affects overall survival in cancer patients irrespective of racial/ethnic and SES differences. Reducing comorbidity burden can reduce some, but not all, of the mortality risk associated with lower SES.
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Etnicidad , Neoplasias , Humanos , Factores Socioeconómicos , Estudios Retrospectivos , Clase Social , Neoplasias/epidemiología , ComorbilidadRESUMEN
Eosinophilia is a rare presentation of acute lymphoblastic leukemia (ALL) within the pediatric population. In this report, we present a patient with pre-B ALL and eosinophilia in the setting of an isocitrate dehydrogenase-2 gene mutation. These mutations have been described in patients with acute myeloid leukemia but in very few patients with ALL.
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Eosinofilia , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Eosinofilia/genética , Humanos , Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/genética , Mutación , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMEN
PURPOSE: We evaluated the influence of race/ethnicity and geocoded socioeconomic status (SES) on all-cause mortality in cancer patients with health insurance. METHODS: We identified adults diagnosed with eight common cancers from 2009 to 2014 from the California Cancer Registry and followed them through 2017 (8 years maximum). We calculated person-year mortality rates by race/ethnicity and SES. Adjusted hazard ratios for the association between overall mortality and race/ethnicity and SES were estimated using Cox proportional hazards models accounting for other demographics, stage at diagnosis, and cancer treatments. RESULTS: A total of 164,197 adults were diagnosed with cancer originating from breast, prostate, lung, colon, skin melanoma, uterus, kidney, and bladder. For all race/ethnic groups combined, the mortality rates from lowest to highest SES groups were 112.1/1000 PY (lowest); 100.2/1000 PY (lower-middle); 91.2/1000 PY (middle); 79.1/1000 PY (upper-middle); and 63.5/1000 PY (upper). These rates suggest that person with lowest SES have a markedly increased mortality risk after cancer diagnosis even if they have health insurance. In multivariable analyses, those in the lowest SES group had a 40-78% increased risk of all-cause mortality compared to those in the upper SES group across all race/ethnicities. For example, within African Americans, the adjusted mortality risk was up to 61% higher (HR 1.61, 95% CI 1.41-1.83) in the lowest SES group compared to the highest SES group. CONCLUSION: This study suggests disparities in overall mortality risk after cancer diagnoses persist even in a cohort with health insurance, and that SES is an important driver of this disparity.
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Seguro de Salud , Neoplasias/etnología , Neoplasias/mortalidad , Adulto , Anciano , California , Etnicidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Sistema de Registros , Clase Social , Factores SocioeconómicosRESUMEN
BACKGROUND: Hodgkin lymphoma (HL) is a leading cancer diagnosis for adolescents and young adults (AYAs), with an overall 5-year survival rate of >80%. However, to the authors' knowledge, little is known regarding posttreatment patterns of care. In the current study, the authors characterized the use of guideline-recommended services in a cohort of AYA survivors of HL in Kaiser Permanente Southern California. METHODS: Patients with HL who were diagnosed between ages 15 and 39 years between 2000 and 2010 were identified. The authors calculated the number of patients who received recommended short-term care within 2 years after treatment cessation for those who remained enrolled and alive from 2001 through 2015. Use of recommended late-effects screening for breast cancer and cardiovascular disease was examined. Logistic regression was used to evaluate the association between receipt of recommended care and patient, cancer, and treatment characteristics. RESULTS: A total of 354 patients were identified, with a mean age at the time of diagnosis of 26 years (standard deviation, 6.9 years). Approximately 12% of patients had stage I disease, 59% had stage II disease, 17% had stage III disease, and 13% of patients had stage IV disease. Nearly all patients received chemotherapy (95%), 51% received radiotherapy, and 5% received care from a pediatric oncologist. Overall, approximately 49% of patients received recommended short-term care. Of those patients eligible for cardiovascular screening at 10 years posttreatment (60 patients), 53% received at least 1 screening. Of those patients eligible for breast cancer screening (21 patients), approximately 50% underwent at least 1 screening. Regression results indicated that those patients treated by a pediatric oncologist were >3 times as likely to receive recommended short-term care. CONCLUSIONS: The results of the current study highlight gaps in the delivery of posttreatment care to AYA survivors of HL. By determining areas in need of improvement, these findings can guide the development of tailored interventions with which to improve care.
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Atención Ambulatoria , Supervivientes de Cáncer/estadística & datos numéricos , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/rehabilitación , Aceptación de la Atención de Salud/estadística & datos numéricos , Cooperación del Paciente/estadística & datos numéricos , Adolescente , Adulto , Atención Ambulatoria/normas , Atención Ambulatoria/estadística & datos numéricos , Atención a la Salud/estadística & datos numéricos , Femenino , Enfermedad de Hodgkin/psicología , Humanos , Masculino , Participación del Paciente/estadística & datos numéricos , Supervivencia , Adulto JovenRESUMEN
AIMS: Septal reduction is needed for hypertrophic obstructive cardiomyopathy (HOCM) patients with severe left ventricular outflow tract (LVOT) gradients and symptoms despite medication. Myectomy cannot be performed in all. Alcohol septal ablation cannot be performed in 5-15% due to technical difficulties. A method of delivering percutaneous tissue damage to the septum that is not reliant on coronary anatomy is desirable. To directly ablate the interventricular septum at the mitral valve (MV) systolic anterior motion (SAM)-septal contact point using radiofrequency (RF) energy guided by CARTOSound. METHODS AND RESULTS: Five patients underwent RF ablation (RFA); we describe follow-up at 6 months in four patients. Intracardiac echocardiography (ICE) images are merged with CARTO to create a shell of the cardiac chambers. The SAM-septal contact area is marked from ICE images and mapped on to the CARTO shell; this becomes the target for RF delivery. Conduction tissue is mapped and avoided where possible. Twenty-eight to 42 min of RF energy was delivered to the target area using retrograde aortic access and SmartTouch catheters. Resting LVOT gradient improved from 64.2 (±50.6) to 12.3 (±2.5) mmHg. Valsalva/exercise-induced gradient reduced from 93.5 (±30.9) to 23.3 (±8.3) mmHg. Three patients improved New York Heart Association status from III to II, one patient improved from class III to I. Exercise time on bicycle ergometer increased from 612 to 730 s. Cardiac magnetic resonance shows late gadolinium enhancement up to 8 mm depth at LV target myocardium. One patient died following a significant retroperitoneal haemorrhage. CONCLUSION: Radiofrequency ablation using CARTOSound(®) guidance is accurate and effective in treating LVOT gradients in HOCM in this preliminary group of patients.
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Mapeo del Potencial de Superficie Corporal/métodos , Cardiomiopatía Hipertrófica/cirugía , Ablación por Catéter/métodos , Ecocardiografía/métodos , Cirugía Asistida por Computador/métodos , Obstrucción del Flujo Ventricular Externo/cirugía , Anciano , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal/métodos , Resultado del Tratamiento , Obstrucción del Flujo Ventricular Externo/diagnóstico , Obstrucción del Flujo Ventricular Externo/etiología , Tabique Interventricular/diagnóstico por imagen , Tabique Interventricular/cirugíaRESUMEN
OBJECTIVES: It has been suggested that statins exert potential anti-tumor effects. The relationship between statin use and outcomes in pancreatic cancer is controversial. We hypothesized that statin use at baseline would impact survival among patients with early-stage pancreatic cancer and that the effect might vary by individual statin agent. METHODS: We conducted a retrospective cohort study on data from an integrated healthcare system. We included patients with pancreatic cancer stage I-IIb who underwent resection for curative intent between January 2005 and January 2011. Baseline statin use was characterized as any prior use as well as active use of either simvastatin or lovastatin. Intensity of exposure was calculated as average daily dose prior to surgery. Overall and disease-free survival was assessed from surgery until the end of study (April 2014). We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the impact of baseline statin use on survival, adjusting for age, sex, Charlson comorbidity score, resection margin, disease stage, and receipt of adjuvant chemotherapy. RESULTS: Among 226 patients, 71 (31.4%) had prior simvastatin use and 27 (11.9%) had prior lovastatin use at baseline. Prior simvastatin but not lovastatin use was associated with improved survival (median 28.5 months (95% confidence limit (CL) 20.8, 38.4) for simvastatin vs. 12.9 months (9.6, 15.5) for lovastatin vs. 16.5 months (14.1, 18.9) for non-statin users; log-rank P=0.0035). In Cox regression, active simvastatin use was independently associated with reduced risk for mortality (adjusted hazard ratio (HR) 0.56 (95% CL 0.38, 0.83), P=0.004) and risk for recurrence (adjusted HR 0.61 (0.41, 0.89), P=0.01). Survival improved significantly among patients who received moderate-high-intensity (median 42.1 months (24.0,52.7)) doses compared with those who received low-intensity doses of simvastatin (median 14.1 months (8.6, 23.8), log-rank P=0.03). CONCLUSIONS: The effects of statins varied by agent and dose. Active use of moderate-high-dose simvastatin at baseline was associated with improved overall and disease-free survival among patients undergoing resection for pancreatic cancer.
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Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/cirugía , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Lovastatina/administración & dosificación , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/cirugía , Simvastatina/administración & dosificación , Anciano , Carcinoma Ductal Pancreático/patología , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/patología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Hypertrophic cardiomyopathy is a common inherited cardiac condition where the myocardium progressively thickens in the absence of abnormal loading conditions. Left ventricular hypertrophy often leads to outflow tract obstruction, and this confers significant mortality and morbidity implications. Septal reduction therapies aim to relieve the obstruction in an attempt to reduce the burden of symptoms and potentially improve prognosis. However, both surgical and catheter-based approaches to septal reduction carry risks. At present, international guidelines and expert consensus statements suggest surgical myomectomy is the gold-standard treatment. In this point-counterpoint review, we discuss why in our opinion this recommendation should be reconsidered. We hope to cover the history of catheter based septal reduction therapies and the significant advances made over the last two decades. We also hope to show why we believe the current evidence shows catheter-based alcohol septal ablation is superior to surgical myomectomy.
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Cardiomiopatía Hipertrófica , Ablación por Catéter , Obstrucción del Flujo Ventricular Externo , Humanos , Cardiomiopatía Hipertrófica/terapia , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/diagnóstico , Obstrucción del Flujo Ventricular Externo/etiología , Obstrucción del Flujo Ventricular Externo/diagnóstico , Obstrucción del Flujo Ventricular Externo/cirugía , Obstrucción del Flujo Ventricular Externo/terapia , Ablación por Catéter/métodos , Tabiques Cardíacos/cirugíaRESUMEN
Adolescents, young adults with cancer receive limited psychosocial and spiritual support near death.
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Cuidados Paliativos al Final de la Vida , Neoplasias , Cuidado Terminal , Humanos , Adolescente , Adulto Joven , Neoplasias/terapia , Neoplasias/psicología , Calidad de VidaRESUMEN
Numerous guidelines on the diagnosis and management of hypertrophic cardiomyopathy (HCM) have been published, by learned societies, over the past decade. Although helpful they are often long and less adapted to nonexperts. This writing panel was challenged to produce a document that grew as much from years of practical experience as it did from the peer-reviewed literature. As such, rather than produce yet another set of guidelines, we aim herein to deliver a concentrate of our own experiential learning and distill for the reader the essence of effective and appropriate HCM care. This Clinical Practice Update on HCM is therefore aimed at general cardiologists and other cardiovascular practitioners rather than for HCM specialists. We set the stage with a description of the condition and its clinical presentation, discuss the central importance of "obstruction" and how to look for it, review the role of cardiac magnetic resonance imaging, reflect on the appropriate use of genetic testing, review the treatment options for symptomatic HCM-crucially including cardiac myosin inhibitors, and deal concisely with practical issues surrounding risk assessment for sudden cardiac death, and management of the end-stage HCM patient. Uniquely, we have captured the pediatric experience on our panel to discuss appropriate differences in the management of younger patients with HCM. We ask the reader to remember that this document represents expert consensus opinion rather than dogma and to use their best judgement when dealing with the HCM patient in front of them.
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BACKGROUND: Adolescents and young adults frequently receive chemotherapy near death. We know less about the use of targeted agents and immunotherapy or trends over time. METHODS: We conducted a retrospective cohort study of 1836 adolescents and young adults with cancer who died between 2009 and 2019 after receiving care at 1 of 3 sites (Dana-Farber Cancer Institute, Kaiser Permanente Northern California, and Kaiser Permanente Southern California). We reviewed electronic health data and medical records to examine use of cancer-directed therapy in the last 90 days of life, including chemotherapy, targeted therapy, immunotherapy, and investigational drugs. RESULTS: Over the study period, 35% of adolescents and young adults received chemotherapy in the last 90 days of life; 24% received targeted therapy, 7% immunotherapy, and 5% investigational drugs. Additionally, 56% received at least 1 form of systemic cancer-directed therapy in the last 90 days of life. After adjustment for patient sex, race, ethnicity, age, site of care, diagnosis, and years from diagnosis to death, the proportion of adolescents and young adults receiving targeted therapy (odds ratio [OR] = 1.05 per year of death, 95% confidence interval [CI] = 1.02 to 1.10; P = .006), immunotherapy (OR = 1.27, 95% CI = 1.18 to 1.38; P < .0001), and any cancer-directed therapy (OR = 1.04, 95% CI = 1.01 to 1.08; P = .01) in the last 90 days of life increased over time. CONCLUSIONS: More than half of adolescents and young adults receive cancer therapy in the last 90 days of life, and use of novel agents such as targeted therapy and immunotherapy is increasing over time. Although some adolescents and young adults may wish to continue cancer therapy while living with advanced disease, efforts are needed to ensure that use of cancer-directed therapy meets preferences of adolescents and young adults approaching death.
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Inmunoterapia , Neoplasias , Cuidado Terminal , Humanos , Adolescente , Masculino , Femenino , Neoplasias/terapia , Neoplasias/mortalidad , Neoplasias/tratamiento farmacológico , Adulto Joven , Estudios Retrospectivos , Adulto , Inmunoterapia/métodos , Terapia Molecular Dirigida , California/epidemiología , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: High-dose chemotherapy with autologous hematopoietic progenitor cell rescue (AuHPCR) for pediatric patients with brain tumors has become an important therapeutic modality to avoid or delay the long-term effects of cranial irradiation. Data on post-AuHPCR infectious complications in this population are lacking. This single institution retrospective review reports the prophylactic practices and infections in the first year following AuHPCR in pediatric patients with brain tumors. PROCEDURE: The medical record of patients who underwent AuHPCR for the treatment of a malignant brain tumor at Children's Hospital Los Angeles between 1988 and 2010 were reviewed. Patients without prior irradiation who were free of disease at 1 year without additional chemotherapy were evaluated for all infectious disease complications occurring from time of neutrophil engraftment to 1 year post-AuHPCR. RESULTS: Forty-three of the 115 eligible patients were included. The median time to neutrophil engraftment was 11 days (range: 8-43 days), and 20 Grade III/IV (no Grade V) infectious episodes developed in 15 patients (35%). Fourteen episodes of bacteremia (70%) were catheter-related, predominantly gram-negative (71%), and polymicrobial (50%). There were no fungal or pneumocystis infections and only 1 of 25 (4%) at-risk patients developed VZV reactivation. CONCLUSIONS: These data suggest patients with brain tumors undergoing AuHPCR have few late-occurring non-catheter-related post-transplant infections indicating that prophylaxis practices were sufficient. Central lines should be removed soon after engraftment, but those with central line infections should receive adequate treatment including gram-negative coverage. In addition, only at-risk patients who receive further irradiation may benefit from VZV reaction prophylaxis.
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Neoplasias Encefálicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Control de Infecciones/métodos , Infecciones/epidemiología , Adolescente , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/prevención & control , Niño , Preescolar , Femenino , Humanos , Lactante , Infecciones/etiología , Masculino , Trasplante Autólogo , Adulto JovenRESUMEN
Obstructive hypertrophic cardiomyopathy is the most common genetically transmitted cardiomyopathy that is associated with significant morbidity and mortality. Despite contemporary treatments and interventions, the management of patients with obstructive hypertrophic cardiomyopathy remains poorly defined compared with other branches of cardiology. In this review, we discuss established and novel therapeutic interventions in patients with obstructive hypertrophic cardiomyopathy with a focus on percutaneous and surgical strategies including surgical myectomy, mitral valve repair or replacement, percutaneous alcohol septal ablation, pacemaker and cardioverter-defibrillator implantation, septal embolization, radiofrequency endocardial catheter ablation, and percutaneous intramyocardial septal radiofrequency ablation.
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AIMS: To compare (1) conventional left ventricular (LV) functional parameters, (2) LV peak strain and strain rate and (3) LV temporal strain and strain rate curves in age, ethnicity and sport-matched athletes with concentric, eccentric and normal LV geometry. METHODS: Forty-five male athletes were categorised according to LV geometry including concentric remodelling/hypertrophy (CON), eccentric hypertrophy (ECC) or normal (NORM). Athletes were evaluated using conventional echocardiography and myocardial speck tracking, allowing the assessment of myocardial strain and strain rate; as well as twist mechanics. RESULTS: Concentric remodelling was associated with an increased ejection fraction (EF) compared to normal geometry athletes (64% (48-78%) and 56% (50-65%), respectively; p < 0.04). No differences in peak myocardial strain or strain rate were present between LV geometry groups including global longitudinal strain (GLS; CON -16.9% (-14.9-20.6%); ECC -17.9% (-13.0-22.1%); NORM -16.9% (-12.8-19.4%)), global circumferential strain (GCS; CON -18.1% (-13.5-24.5%); ECC -18.7% (-15.6-22.4%); NORM -18.0% (-13.5-19.7%)), global radial strain (GRS; CON 42.2% (30.3-70.5%); ECC 50.0% (39.2-60.0%); NORM 40.6 (29.9-57.0%)) and twist (CON 14.9° (3.7-25.3°); ECC 12.5° (6.3-20.8°); NORM 13.2° (8.8-24.2°)). Concentric and eccentric remodelling was associated with alterations in temporal myocardial strain and strain rate as compared to normal geometry athletes. CONCLUSION: Physiological concentric and eccentric remodelling in the athletes heart is generally associated with normal LV function; with concentric remodelling associated with an increased EF. Physiological concentric and eccentric remodelling in the athletes heart has no effect on peak myocardial strain but superior deformation and untwisting is unmasked when assessing the temporal distribution.
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BACKGROUND: Lower socioeconomic status (SES) affects health care delivery and is associated with worse outcomes. Integrated healthcare systems (IHS) may help reduce barriers to health care and affect outcomes. Our aim was to compare outcomes of colon cancer cases diagnosed at the largest IHS in California, Kaiser Permanente Southern California (KPSC), to other insured patients (OI) to determine how SES influences mortality. METHODS: This retrospective cohort study included insured adults in southern California diagnosed with colon cancer between 2009 and 2014, using data from the California Cancer Registry, and followed through 2017. Main outcome was all-cause mortality. Person-year mortality rates were calculated for two groups, KPSC and OI. Multivariable hazard ratios were calculated for association between SES quintiles and mortality. RESULTS: Total of 15 923 patients were diagnosed with colon cancer, 4195 patients (26.3%) within KPSC and 11 728 patients (73.7%) in OI. The overall mortality rate per 1000 person-years (PY) was lower in KPSC [103.8/1000 PY (95% CI:98.5-109.3)] compared to OI [139.3/1000 PY (95% CI:135.2-143.4)]. Compared to the highest SES group, the lowest SES group did not experience higher mortality risk in the KPSC population, after adjusting for race/ethnicity and other factors (HR, 95% CI = 1.13, .93-1.38). However, in OI patients, lowest and lower-middle SES groups had higher mortality risk compared to the highest SES group (HR, 95% CI = 1.26, 1.13-1.40 and 1.28, 1.16-1.41, respectively). DISCUSSION: Lower SES was associated with higher mortality risk within the OI group; however, within KPSC no such association was observed. Care coordination in IHS settings mitigate SES-related mortality differences.
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Neoplasias del Colon , Prestación Integrada de Atención de Salud , Adulto , Humanos , Estudios Retrospectivos , Clase Social , Etnicidad , Neoplasias del Colon/terapiaRESUMEN
These guidelines form an update of the BSE guideline protocol for the assessment of restrictive cardiomyopathy (Knight et al. in Echo Res Prac, 2013). Since the original recommendations were conceived in 2013, there has been an exponential rise in the diagnosis of cardiac amyloidosis fuelled by increased clinician awareness, improvements in cardiovascular imaging as well as the availability of new and effective disease modifying therapies. The initial diagnosis of cardiac amyloidosis can be challenging and is often not clear-cut on the basis of echocardiography, which for most patients presenting with heart failure symptoms remains the first-line imaging test. The role of a specialist echocardiographer will be to raise the suspicion of cardiac amyloidosis when appropriate, but the formal diagnosis of amyloid sub-type invariably requires further downstream testing. This document seeks to provide a focused review of the literature on echocardiography in cardiac amyloidosis highlighting its important role in the diagnosis, prognosis and screening of at risk individuals, before concluding with a suggested minimum data set, for use as an aide memoire when reporting.
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PURPOSE: Adolescents and young adults (AYAs) with cancer receive high rates of medically intensive measures at the end of life. This study aimed to characterize the prevalence and timing of conversations about goals of care and advance care planning among AYAs at the end of life as one potential influence on care received. METHODS: This was a review of electronic health data and medical records for 1,929 AYAs age 12-39 years who died after receiving care at one of three sites between 2003 and 2019, including documented conversations about goals of care and advance care planning, and care received. RESULTS: A majority of AYAs were female (54%) and White (61%); 12% were Asian, 8% Black, and 27% Hispanic. Most patients had documented discussions about prognosis (86%), goals of care (83%), palliative care (79%), hospice (79%), and preferred location of death (64%). When last documented goals of care were evaluated, 69% of patients wanted care focused on palliation; however, 29% of those with palliative goals spent time in the intensive care unit (ICU) in the last month of life, and 32% had multiple emergency room (ER) visits. When goals-of-care discussions happened earlier, >30 days before death, AYAs were less likely to receive chemotherapy in the last 14 days of life (P = .001), ICU care (P < .001), ER visits (P < .001), and hospitalizations in the last month (P < .001). CONCLUSION: High rates of medically intensive measures among AYAs near the end of life do not appear to be the result of a lack of discussions about goals of care and advance care planning. Although some interventions may be used to support palliative goals, earlier discussions have potential to reduce late-life intensive measures.
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Planificación Anticipada de Atención , Neoplasias , Cuidado Terminal , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Adulto Joven , Muerte , Neoplasias/terapia , Cuidados PaliativosRESUMEN
Synthetic biology has developed sophisticated cellular biosensors to detect and respond to human disease. However, biosensors have not yet been engineered to detect specific extracellular DNA sequences and mutations. Here, we engineered naturally competent Acinetobacter baylyi to detect donor DNA from the genomes of colorectal cancer (CRC) cells, organoids, and tumors. We characterized the functionality of the biosensors in vitro with coculture assays and then validated them in vivo with sensor bacteria delivered to mice harboring colorectal tumors. We observed horizontal gene transfer from the tumor to the sensor bacteria in our mouse model of CRC. This cellular assay for targeted, CRISPR-discriminated horizontal gene transfer (CATCH) enables the biodetection of specific cell-free DNA.
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Acinetobacter , Técnicas Biosensibles , Ácidos Nucleicos Libres de Células , Neoplasias Colorrectales , ADN de Neoplasias , Animales , Humanos , Ratones , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , ADN de Neoplasias/análisis , Mutación , Acinetobacter/genética , Ácidos Nucleicos Libres de Células/análisis , BioingenieríaRESUMEN
OBJECTIVES: To develop a COVID-19-specific deterioration index for hospitalized patients: the COVID Hospitalized Patient Deterioration Index (COVID-HDI). This index builds on the proprietary Epic Deterioration Index, which was not developed for predicting respiratory deterioration events among patients with COVID-19. STUDY DESIGN: A retrospective observational cohort was used to develop and validate the COVID-HDI model to predict respiratory deterioration or death among hospitalized patients with COVID-19. Deterioration events were defined as death or requiring high-flow oxygen, bilevel positive airway pressure, mechanical ventilation, or intensive-level care within 72 hours of run time. The sample included hospitalized patients with COVID-19 diagnoses or positive tests at Kaiser Permanente Southern California between May 3, 2020, and October 17, 2020. METHODS: Machine learning models and 118 candidate predictors were used to generate benchmark performance. Logit regression with least absolute shrinkage and selection operator and physician input were used to finalize the model. Split-sample cross-validation was used to train and test the model. RESULTS: The area under the receiver operating curve was 0.83. COVID-HDI identifies patients at low risk (negative predictive value [NPV] > 98.5%) and borderline low risk (NPV > 95%) of an event. Of all patients, 74% were identified as being at low or borderline low risk at some point during their hospitalization and could be considered for discharge with or without home monitoring. A high-risk group with a positive predictive value of 51% included 12% of patients. Model performance remained high in a recent cohort of patients. CONCLUSIONS: COVID-HDI is a parsimonious, well-calibrated, and accurate model that may support clinical decision-making around discharge and escalation of care.
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COVID-19 , Humanos , Cuidados Críticos , Hospitalización , Valor Predictivo de las Pruebas , Estudios Retrospectivos , SARS-CoV-2RESUMEN
AIMS: Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator. In preclinical and clinical studies in diabetes, trientine is associated with reduced LVH and fibrosis, and improved mitochondrial function and energy metabolism. Trientine was associated with improvements in cardiac structure and function in an open-label study in patients with HCM. METHODS: The Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy (TEMPEST) trial is a multicentre, double-blind, parallel group, 1:1 randomised, placebo-controlled phase II trial designed to evaluate the efficacy and mechanism of action of trientine in patients with HCM. Patients with a diagnosis of HCM according to the European Society of Cardiology Guidelines and in New York Heart Association classes I-III are randomised to trientine or matching placebo for 52 weeks. Primary outcome is change in left ventricular (LV) mass indexed to body surface area, measured using cardiovascular magnetic resonance. Secondary efficacy objectives will determine whether trientine improves exercise capacity, reduces arrhythmia burden, reduces cardiomyocyte injury, improves LV and atrial function, and reduces LV outflow tract gradient. Mechanistic objectives will determine whether the effects are mediated by cellular or extracellular mass regression and improved myocardial energetics. CONCLUSION: TEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM. TRIAL REGISTRATION NUMBERS: NCT04706429 and ISRCTN57145331.
Asunto(s)
Cardiomiopatía Hipertrófica , Trientina , Humanos , Trientina/uso terapéutico , Cobre/uso terapéutico , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/tratamiento farmacológico , Cardiomiopatía Hipertrófica/complicaciones , Corazón , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/prevención & control , FibrosisRESUMEN
Cardiac sarcoidosis and cystic fibrosis (CF) are both rare conditions and their co-existence has not previously been noted in adults. For the first time we report a case of isolated cardiac sarcoidosis in a woman with CF, and discuss the possible combined aetiological factors. As the life expectancy of people with CF continues to increase, clinicians should be aware of the emergence of concomitant inflammatory conditions typically diagnosed in adulthood, and the diagnostic challenges this may present.