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BACKGROUND: Although most patients with cancer prefer to know their prognosis, prognostic communication between oncologists and patients is often insufficient. Targeted therapies for lung cancer improve survival yet are not curative and produce variable responses. This study sought to describe how oncologists communicate about prognosis with patients receiving targeted therapies for lung cancer. METHODS: This qualitative study included 39 patients with advanced lung cancer with targetable mutations, 14 caregivers, and 10 oncologists. Semistructured interviews with patients and caregivers and focus groups or interviews with oncologists were conducted to explore their experiences with prognostic communication. One oncology follow-up visit was audio-recorded per patient. A framework approach was used to analyze interview transcripts, and a content analysis of patient-oncologist dialogue was conducted. Themes were identified within each source and then integrated across sources to create a multidimensional description of prognostic communication. RESULTS: Six themes in prognostic communication were identified: Patients with targetable mutations develop a distinct identity in the lung cancer community that affects their information-seeking and self-advocacy; oncologists set high expectations for targeted therapy; the uncertain availability of new therapies complicates prognostic discussions; patients and caregivers have variable information preferences; patients raise questions about progression by asking about physical symptoms or scan results; and patients' expectations of targeted therapy influence their medical decision-making. CONCLUSIONS: Optimistic patient-oncologist communication shapes the expectations of patients receiving targeted therapy for lung cancer and affects their decision-making. Further research and clinical guidance are needed to help oncologists to communicate uncertain outcomes effectively.
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Neoplasias Pulmonares , Neoplasias , Oncologistas , Comunicação , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias/terapia , Relações Médico-Paciente , Medicina de Precisão , PrognósticoRESUMO
OBJECTIVES: Determine the true incidence and time course of atrial fibrillation (AF) after patent foramen ovale closure (PFOc) using implantable loop recorders (ILR) placed during cryptogenic stroke evaluation. BACKGROUND: Published trials report a 2%-6.6% incidence of postimplant atrial fibrillation (PIAF) after PFOc, which is probably a gross underestimation, as only patients presenting in AF were captured. Episodes of paroxysmal and silent AF would have been missed. METHODS: Of 761 patients who underwent PFOc at a single center between January 2016 and December 2020, 35 patients had an ILR implanted before PFOc, without documentation of AF, and had ≥1 month of monitoring post-PFOc. The incidence, onset, and conclusion of AF episodes were determined from a review of patient records. RESULTS: The mean duration of ILR monitoring was 54.6 ± 39.4 weeks after PFOc. AF occurred in 13/35 (37%) patients. PFOc patients who developed PIAF were older than those who did not (62 ± 11 vs. 52 ± 14 years, p = 0.03). In 12/13, the initial PIAF event occurred within 4 weeks of PFOc, with the greatest frequency around 2 weeks and conclusion by 12 weeks in all. No recurrent strokes occurred during ILR monitoring. CONCLUSION: The actual incidence of PIAF was far greater than previously reported and was significantly associated with older age at PFOc. The timing of PIAF onset and termination were consistent with a postimplant inflammatory mechanism. The higher actual PIAF incidence underscores its low stroke potential in this population. A larger prospective trial is required to validate these preliminary results.
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Fibrilação Atrial , Forame Oval Patente , Acidente Vascular Cerebral , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Forame Oval Patente/complicações , Forame Oval Patente/diagnóstico por imagem , Forame Oval Patente/epidemiologia , Humanos , Incidência , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
OBJECTIVE: Assess clinical performance of a new device for transcatheter closure of atrial septal defect (ASD). BACKGROUND: Previously-approved ASD Closure devices have known limitations. Device erosion has been associated with the AMPLATZER® septal occluder in patients with retro-aortic rim deficiency (<5 mm), while defects ≥18 mm are too large for the GORE® CARDIOFORM septal occluder. The GORE® CARDIOFORM ASD occluder (GCA), a hybrid of the approved devices, was designed to expand the eligible ASD population. METHODS: One-hundred and twenty-five ASD patients were enrolled in a prospective, multicenter registry. Descriptive clinical endpoints included: technical implant success, closure success, serious adverse events (SAE), clinically significant new arrhythmia, and wire frame fracture. Procedural outcomes and adverse events were adjudicated by an Echocardiography Core Lab and Independent Data Review Board, respectively. RESULTS: Median subject age was 12.3 years (range 2.9-84.7), with 72% of patients ≤18 years old. Median ASD stop-flow diameter was 17.0 mm (8.0-30.0), with 43% ≥18 mm. Deficient retro-aortic rim occurred in 57% of subjects, and 30% had both diameter ≥ 18 mm and deficient rim. Technical Implant Success was achieved in 120/125 (96%), though three devices were removed within 24 hr. At the scheduled 6-month evaluation, 112/117 returned for evaluation. All 112 had closure success. SAE occurred in 6/125 (4.8%) and 6/125 (4.8%) had clinically significant new arrhythmia. Wire frame fractures occurred in 37/104 (36%), without any associated clinical sequelae, residual shunt, or device instability. CONCLUSION: The GCA performed effectively and safely in this initial cohort, and led to FDA approval based on this data.
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Cateterismo Cardíaco/instrumentação , Comunicação Interatrial/terapia , Dispositivo para Oclusão Septal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco/efeitos adversos , Criança , Pré-Escolar , Feminino , Comunicação Interatrial/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Desenho de Prótese , Sistema de Registros , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
Chronic graft-versus-host disease (GVHD) is one of most common complications following allogeneic hematopoietic cell transplantation (HCT) and the most significant contributor to morbidity and nonrelapse mortality. The physical burdens and psychosocial difficulties of these patients have not been described systematically. An exploration into the rates and correlates of mood and quality of life (QOL) in patients with chronic GVHD is necessary to develop a clinically relevant, evidence-based intervention to promote well-being. From July 2015 to July 2017, adult allogeneic HCT survivors with established moderate to severe chronic GVHD (Nâ¯=â¯52) enrolled in a prospective, longitudinal study at a tertiary academic center. We examined the rates and correlates of depression and anxiety symptoms (Hospital Anxiety and Depression Scale) and explored whether constructs including coping strategies (Coping Inventory for Stressful Situations), symptom burden (Lee Symptom Assessment Scale), physical functioning (Human Activity Profile), and perceived social support (Medical Outcomes Study Social Support Survey) predicted QOL trajectory over time (Functional Assessment of Cancer Therapy-Bone Marrow Transplant) at the baseline, 3-month, and 6-month follow-up. Analyses adjusted for age, sex, chronic GVHD severity, and time since chronic GVHD diagnosis. At the baseline, 3-month, and 6-month follow-up, 32.7%, 31.1%, and 37.8% of patients reported clinically significant depression symptoms, and 30.8%, 20.0%, and 36.4% reported clinically elevated anxiety symptoms, respectively. Adjusting for covariates, greater use of negative emotion-oriented coping (ßâ¯=â¯0.20, Pâ¯=â¯.002), less use of task-oriented coping (ßâ¯=â¯-0.10, Pâ¯=â¯.021), worse physical functioning (ßâ¯=â¯-0.07, Pâ¯=â¯.004), and higher symptom burden (ßâ¯=â¯0.07, Pâ¯=â¯.002) were independently associated with depression symptoms at baseline. Greater use of negative emotion-oriented coping (ßâ¯=â¯0.28, P < .001) and worse physical functioning (ßâ¯=â¯-0.05, Pâ¯=â¯.034) were independently associated with anxiety at baseline. Patients who used more negative emotion-oriented coping (ßâ¯=â¯-0.58, Pâ¯=â¯.035), had less task-oriented (ßâ¯=â¯0.40, Pâ¯=â¯.028) and social diversion-oriented coping (ßâ¯=â¯0.35, Pâ¯=â¯.039), and had higher symptom burden (ßâ¯=â¯-0.30, Pâ¯=â¯.001), worse physical functioning (ßâ¯=â¯0.32, P < .001), and lower perceived social support (ßâ¯=â¯6.47, Pâ¯=â¯.003) at baseline reported poorer QOL over time. The unmet physical and psychosocial needs of patients with chronic GVHD are substantial and warrant investigation into evidence-based interventions that may improve QOL and mood by targeting modifiable psychosocial constructs identified in this study.
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Afeto , Ansiedade/psicologia , Depressão/psicologia , Doença Enxerto-Hospedeiro/psicologia , Transplante de Células-Tronco Hematopoéticas/psicologia , Qualidade de Vida , Estresse Psicológico/psicologia , Adulto , Idoso , Ansiedade/terapia , Depressão/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Estresse Psicológico/terapiaRESUMO
INTRODUCTION: Percutaneous left atrial appendage closure (LAAC) is typically performed utilizing transesophageal echocardiography (TEE) and fluoroscopy. Intracardiac echocardiography (ICE) can be a suitable alternative to guide implantation. Given the limited data, we performed a meta-analysis of all studies that compared ICE vs TEE for percutaneous LAAC. METHODS: A comprehensive literature search was performed in PubMed, Embase, Scopus, Google Scholar, and major scientific conference sessions for published abstracts and manuscripts until 1 August 2018. Studies reporting clinical outcomes comparing TEE vs ICE for endocardial LAAC in human subjects aged greater than or equal to 18 years were included. Two investigators independently extracted the data and individual quality assessment was performed. The analysis was performed using Cochrane Collaboration software, RevMan 5.3. RESULTS: Five eligible studies consisting of 1157 patients (ICE-391 patients and TEE-766 patients) were included. Four studies were retrospective and one was prospective, nonrandomized. Two studies included Watchman, two included the Amplatzer Cardiac Plug/Amulet device, and one included both devices. There was no significant difference in CHA2DS2VASC or HAS-BLED scores between both groups. There was no significant difference in acute procedural success between ICE vs TEE (risk ratio, 1.01; 95% CI, 0.99-1.04; P = 0.24). There was no significant difference in fluoroscopy time (mean difference [MD], 1.84 minutes; 95% CI, 0.59-4.27; P = 0.14) and total procedure time (MD, -5.06 minutes; 95% CI, -24.6-14.4; P = 0.61) between both groups. There was also no significant difference in complications including pericardial tamponade, device embolization, and stroke between both groups. CONCLUSION: In our meta-analysis, ICE was as effective as TEE during percutaneous LAAC.
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Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/terapia , Cateterismo Cardíaco , Ecocardiografia Transesofagiana , Idoso , Apêndice Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Resultado do TratamentoRESUMO
Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.
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Biota , Mudança Climática/história , Extinção Biológica , Atividades Humanas/história , Mamíferos/fisiologia , Animais , Teorema de Bayes , Bison , DNA Mitocondrial/análise , DNA Mitocondrial/genética , Europa (Continente) , Fósseis , Variação Genética , Geografia , História Antiga , Cavalos , Humanos , Mamíferos/genética , Mamutes , Dados de Sequência Molecular , Dinâmica Populacional , Rena , Sibéria , Especificidade da Espécie , Fatores de TempoRESUMO
The use of short-term indicators for understanding patterns and processes of biodiversity loss can mask longer-term faunal responses to human pressures. We use an extensive database of approximately 18,700 mammalian zooarchaeological records for the last 11,700 years across Europe to reconstruct spatio-temporal dynamics of Holocene range change for 15 large-bodied mammal species. European mammals experienced protracted, non-congruent range losses, with significant declines starting in some species approximately 3000 years ago and continuing to the present, and with the timing, duration and magnitude of declines varying individually between species. Some European mammals became globally extinct during the Holocene, whereas others experienced limited or no significant range change. These findings demonstrate the relatively early onset of prehistoric human impacts on postglacial biodiversity, and mirror species-specific patterns of mammalian extinction during the Late Pleistocene. Herbivores experienced significantly greater declines than carnivores, revealing an important historical extinction filter that informs our understanding of relative resilience and vulnerability to human pressures for different taxa. We highlight the importance of large-scale, long-term datasets for understanding complex protracted extinction processes, although the dynamic pattern of progressive faunal depletion of European mammal assemblages across the Holocene challenges easy identification of 'static' past baselines to inform current-day environmental management and restoration.
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Distribuição Animal , Biodiversidade , Extinção Biológica , Mamíferos/fisiologia , Animais , Arqueologia , Europa (Continente) , Fósseis , Paleontologia , Especificidade da EspécieRESUMO
BACKGROUND: The association of patient foramen ovale (PFO) and migraine headache (migraine) with aura (MA) is well established. Current research suggests a mechanistic link between platelet activation, paradoxical embolization and migraine in some patients. METHODS: Clopidogrel, a platelet inhibitor, was added to existing migraine therapy, as a 4-week open-label trial in 15 women, aged 16-56 years, with severe migraine and documented right to left shunt (RLS). RESULTS: 13/15 had > 50% reduction or complete elimination of migraine symptoms. After completing the trial period, five responders remain on clopidogrel with ongoing benefit at 11.9 ± 4.5 months (6.5-20), one stopped clopidogrel because of side effects. Nine other responders underwent PFO closure and clopidogrel discontinuation. Eight of nine have had ongoing benefit. CONCLUSIONS: Clopidogrel may have a primary prophylactic role in migraine/RLS patients, but may also help select candidates who would benefit from PFO closure. A randomized clinical trial is being established.
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Forame Oval Patente/complicações , Forame Oval Patente/tratamento farmacológico , Enxaqueca com Aura/complicações , Enxaqueca com Aura/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/análogos & derivados , Adolescente , Adulto , Clopidogrel , Feminino , Humanos , Pessoa de Meia-Idade , Ticlopidina/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Immunotherapy has improved survival for patients with melanoma and non-small cell lung cancer (NSCLC). Yet, as responses vary widely, immunotherapy also introduces challenges in prognostic communication. In this study, we sought to explore how patients and caregivers learned about the goal of immunotherapy and their experience of living with uncertainty. MATERIALS AND METHODS: We conducted a qualitative study of patients with stage III or IV melanoma or stage IV NSCLC within 12 weeks of initiating or 12 months of discontinuing immunotherapy, and their caregivers. We conducted in-depth interviews with participants to explore how they learned about immunotherapy from oncology clinicians and how they experienced uncertainty. We used a framework approach to analyze interview transcripts and synthesized concepts into themes. RESULTS: Forty-two patients and 10 caregivers participated; median age was 67 years and most were male (68%), white (95%), married (61%), and had melanoma (62%). We identified four themes: (1) the oncology team shaped participants' hopeful expectations of immunotherapy, including as a potential cure among those with melanoma; (2) distress related to prognostic uncertainty particularly affected patients who experienced toxicity or progressive disease; (3) patients who did not have long-term responses experienced overwhelming disappointment; and (4) some patients and caregivers had conflicting preferences for prognostic information. Participants provided suggestions to improve education and underscored unmet psychosocial needs. CONCLUSION: Patients and caregivers held optimistic expectations of immunotherapy, which resulted in heightened disappointment among the subset with progression or toxicity. Clinicians should elicit information preferences of both patients and caregivers, as these may be disparate. Our results highlight the need to optimize prognostic communication and support for living with uncertainty among patients receiving immunotherapy.
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Cell growth is required for cell cycle progression. The amount of growth required for cell cycle progression is reduced in poor nutrients, which leads to a reduction in cell size. In budding yeast, nutrients can influence cell size by modulating the extent of bud growth, which occurs predominantly in mitosis. However, the mechanisms are unknown. Here, we used mass spectrometry to identify proteins that modulate bud growth in response to nutrient availability. This led to the discovery that nutrients regulate numerous components of the mitotic exit network (MEN), which controls exit from mitosis. A key component of the MEN undergoes gradual multisite phosphorylation during bud growth that is dependent upon bud growth and correlated with the extent of growth. Furthermore, activation of the MEN is sufficient to override a growth requirement for mitotic exit. The data suggest a model in which the MEN ensures that mitotic exit occurs only when an appropriate amount of bud growth has occurred.
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Mitose , Saccharomyces cerevisiae , Transdução de Sinais , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Nutrientes/metabolismo , Fosforilação , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomycetales/metabolismo , Saccharomycetales/crescimento & desenvolvimentoRESUMO
OBJECTIVES: We sought to perform a meta-analysis of randomized controlled trials (RCTs) comparing percutaneous patent-foramen-ovale (PFO) closure with medical therapy for preventing recurrent thromboembolic events after cryptogenic stroke. BACKGROUND: Observational studies suggested that transcatheter PFO closure decreases recurrent events after cryptogenic stroke; however, three recent RCTs failed to demonstrate such benefit. METHODS: Trials were identified from the PubMed and Cochrane databases. Primary endpoint was the composite of transient ischemic attack (TIA) and ischemic cerebrovascular events (CVA). Both intention-to-treat (ITT) and as-treated analyses (AT) were performed. RESULTS: Three RCTs met inclusion criteria. The pooled data provided 2,303 patients, of which 1,150 were in the PFO closure group and 1,153 in the medical therapy group. In the ITT analysis, there were 43 events (3.7%) of the composite end point in the closure group compared with 61 events (5.3%) in the medical therapy group, with a trend in favor of the PFO closure (OR = 0.70; 95% CI, 0.47-1.05, P = 0.08). The incidences of TIA, ischemic CVA, and bleeding were not statistically different between the groups. There was a trend for the more frequent occurrence of atrial fibrillation in the PFO closure group (OR = 3.29; 95% CI, 0.86-12.60, P = 0.08). In the AT analysis, the composite end point was significantly less frequent in the PFO closure group (OR = 0.62; 95% CI, 0.41-0.94, P = 0.02). CONCLUSIONS: In this meta-analysis of contemporary RCTs, successful transcatheter closure of PFO might be more effective than medical therapy alone for the prevention of recurrent thromboembolic events.
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Anticoagulantes/uso terapêutico , Transtornos Cerebrovasculares/prevenção & controle , Forame Oval Patente/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Tromboembolia/prevenção & controle , Anticoagulantes/efeitos adversos , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Cateterismo Cardíaco/mortalidade , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/mortalidade , Distribuição de Qui-Quadrado , Forame Oval Patente/complicações , Forame Oval Patente/diagnóstico , Forame Oval Patente/mortalidade , Humanos , Análise de Intenção de Tratamento , Razão de Chances , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Prevenção Secundária , Tromboembolia/diagnóstico , Tromboembolia/etiologia , Tromboembolia/mortalidade , Resultado do TratamentoRESUMO
Contrast exposure during left atrial appendage occlusion may be harmful in those with chronic kidney disease or allergy. This single-center registry (n = 31) demonstrates the feasibility and safety of zero-contrast percutaneous left atrial appendage occlusion using echocardiography, fluoroscopy, and fusion imaging, with 100% procedural success and no device complications at 45 days.
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Apêndice Atrial , Fibrilação Atrial , Humanos , Ecocardiografia Transesofagiana , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Resultado do Tratamento , Cateterismo Cardíaco/métodos , Ecocardiografia , Meios de Contraste , FluoroscopiaRESUMO
Significant pulmonary regurgitation (PR) and pulmonary stenosis are common after surgical repair of some congenital heart defects. This prospective, single-arm, multicenter trial enrolled patients who underwent transcatheter heart valve (THV) implantation with a SAPIEN 3 valve to treat dysfunctional right ventricular outflow tract (RVOT) conduits or pulmonic surgical valves (≥ moderate PR and/or mean RVOT gradient ≥35 mm Hg). The primary end point was a nonhierarchical composite of THV dysfunction at 1 year comprising RVOT reintervention, ≥ moderate total PR, and mean RVOT gradient >40 mm Hg. A performance goal of <25% of upper confidence interval (CI) was prespecified for the primary end point, using a 95% exact binomial CI. Patients (n = 58) were enrolled between July 5, 2016 and July 17, 2018, with mean age of 32 years. Prestenting was performed in 53.4%. At discharge, the device success was 98.1% (single valve without explant, < moderate PR, gradient <35 mm Hg). At 30 days, there were no major adjudicated adverse clinical events. At 1 year, the primary end point composite was 4.3% (95% CI 0.5 to 14.5). The composite components were 0% (0 of 56) RVOT reintervention, 2.1% (1 of 47) ≥ moderate PR, and 2.1% (1 of 48) mean RVOT gradient >40 mm Hg. No mortality, endocarditis, thrombosis, or stent fracture were reported at 1 year. In conclusion, the SAPIEN 3 THV was safe and effective in patients with dysfunctional RVOT conduits or previously implanted valves in the pulmonic position to 1 year. Clinical trial registration: NCT02744677; https://clinicaltrials.gov/ct2/show/NCT02744677.
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Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Insuficiência da Valva Pulmonar , Valva Pulmonar , Humanos , Adulto , Implante de Prótese de Valva Cardíaca/efeitos adversos , Estudos Prospectivos , Empatia , Cateterismo Cardíaco/efeitos adversos , Resultado do Tratamento , Desenho de Prótese , Fatores de Tempo , Valva Pulmonar/cirurgia , Insuficiência da Valva Pulmonar/cirurgiaRESUMO
Background: The Conformal Left Atrial Appendage System (CLAAS) is a transcatheter implant designed to occlude the left atrial appendage to prevent stroke in patients with nonvalvular atrial fibrillation. The implant incorporates a novel polyurethane polycarbonate-urea foam matrix to enhance device performance. The objective of this study was to characterize the thrombogenicity, sealing, implant integrity, local tissue response, and systemic toxicity of the implant in a healthy canine model. Methods: Devices were evaluated in a chronic canine model using echocardiographic and fluoroscopic guidance (n = 8). Postprocedural echocardiographic evaluation was performed at case completion and at 2, 45, 90, and 150 days. Animals were sacrificed at 90 (n = 4) and 150 (n = 4) days. Necropsy included gross, x-ray, and histologic examination. Results: CLAAS implants were implanted in all animals successfully on the basis of fluoroscopic, intracardiac echo, and transthoracic echo criteria. Although 2 animals were noted to have leaks (1 at implantation and 1 at day 90 post procedure before sacrifice), both were of <5 mm. All left atrial appendages were completely sealed on gross examination. No device-related thrombus, pericardial effusion, or evidence of distal organ emboli was observed. All implants maintained their structural integrity and were well integrated within the tissue. There was no histologic evidence of toxicity noted in the downstream organs or tissues. Conclusions: The CLAAS implant can be deployed providing a good seal for up to 150 days without signs of local or systemic toxicity in a canine model.
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A 79-year-old man with prior bioprosthetic mitral valve replacement presented with progressive shortness of breath and was found to have right upper pulmonary vein stenosis and paravalvular leak diagnosed with the use of multimodal imaging. The patient underwent balloon angioplasty, stenting of the pulmonary vein, and paravalvular leak closure with ultimate resolution of symptoms. (Level of Difficulty: Intermediate.).
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Background: The Serious Illness Care Program has been shown to improve quality and feasibility of value-based end-of-life conversations in primary care. Objectives: To elicit patients' perspectives on serious illness conversations conducted by primary care clinicians. Subjects and Methods: Telephone interviews were conducted with patients at an academic center in the United States, who had a recent serious illness conversation with their primary care clinician. Interviews were audio-recorded and qualitatively analyzed using thematic analysis. Results: A total of eleven patients were enrolled. We identified three major themes: (1) positive emotional experiences are facilitated by established patient-clinician relationships and/or clinicians' skills in navigating emotional challenges, (2) patients appreciate a personalized conversation, and (3) clinicians should orchestrate the experience of the conversation, from preparation through follow-up. Conclusion: Patients appreciate having serious illness conversations in the primary care setting. Future efforts can be focused on improving clinicians' skills in navigating emotional challenges during conversations and implementing system changes to optimize orchestration.
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Planejamento Antecipado de Cuidados , Estado Terminal , Comunicação , Estado Terminal/psicologia , Humanos , Atenção Primária à SaúdeRESUMO
Background: Three-dimensional transesophageal echocardiography (3D-TEE) is the primary imaging tool for left atrial appendage closure planning. The utility of cardiac computed tomography angiography (CCTA) and patient-specific computational models is unknown. Objectives: The purpose of this study was to evaluate the accuracy of the FEops HEARTguide patient-specific computational modeling in predicting appropriate device size, location, and compression of the WATCHMAN FLX compared to intraprocedural 3D-TEE. Methods: Patients with both preprocedural and postprocedural CCTA and 3D-TEE imaging of the LAA who received a WATCHMAN FLX left atrial appendage closure device were studied (n = 22). The FEops HEARTguide platform used baseline CCTA imaging to generate a prediction of device size(s), device position(s), and device dimensions. Blinded (without knowledge of implanted device size/position) and unblinded (implant device size/position disclosed) simulations were evaluated. Results: In 16 (72.7%) patients, the blind simulation predicted the final implanted device size. In these patients, the 3D-TEE measurements were not significantly different and had excellent correlation (Pearson correlation coefficient (r) ≥ 0.90). No patients had peridevice leak after device implant. In the 6 patients for whom the model did not predict the implanted device size, a larger device size was ultimately implanted as per operator preference. The model measurements of the unblinded patients demonstrated excellent correlation with 3D-TEE. Conclusions: This is the first study to demonstrate that the FEops HEARTguide model accurately predicts WATCHMAN FLX device implantation characteristics. Future studies are needed to evaluate if computational modeling can improve confidence in sizing, positioning, and compression of the device without compromising technical success.
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Entry into the cell cycle occurs only when sufficient growth has occurred. In budding yeast, the cyclin Cln3 is thought to initiate cell cycle entry by inactivating a transcriptional repressor called Whi5. Growth-dependent changes in the concentrations of Cln3 or Whi5 have been proposed to link cell cycle entry to cell growth. However, there are conflicting reports regarding the behavior and roles of Cln3 and Whi5. Here, we found no evidence that changes in the concentration of Whi5 play a major role in controlling cell cycle entry. Rather, the data suggest that cell growth triggers cell cycle entry by driving an increase in the concentration of Cln3. We further found that accumulation of Cln3 is dependent upon homologs of mammalian SGK kinases that control cell growth and size. Together, the data are consistent with models in which Cln3 is a crucial link between cell growth and the cell cycle.
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Ciclo Celular/genética , Proliferação de Células/genética , Ciclinas/genética , Proteínas Repressoras/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/fisiologia , Ciclinas/metabolismo , Proteínas Repressoras/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
Fowers et al. (2017) recently made a general argument for virtues as the characteristics necessary for individuals to flourish, given inherent human limitations. For example, people can flourish by developing the virtue of friendship as they navigate the inherent (healthy) human dependency on others. This general argument also illuminates a pathway to flourishing during the COVID-19 pandemic, the risks of which have induced powerful fears, exacerbated injustices, and rendered life and death decisions far more common. Contexts of risk and fear call for the virtue of courage. Courage has emerged more powerfully as a central virtue among medical personnel, first responders, and essential workers. Longstanding inequalities have been highlighted during the pandemic, calling for the virtue of justice. When important personal and public health decisions must be made, the central virtue of practical wisdom comes to the fore. Wise decisions and actions incorporate the recognition of relevant moral concerns and aims, as well as responding in fitting and practical ways to the specifics of the situation. Practicing courage, justice, and practical wisdom illuminates a path to flourishing, even in a pandemic.
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OBJECTIVES: The authors report the first clinical experience with the Conformal Left Atrial Appendage Seal (CLAAS) device. BACKGROUND: The CLAAS device was designed to address the limitations of first-generation left atrial appendage closure (LAAC) devices by providing an implant that is minimally traumatic, can be deployed in a noncoaxial fashion, and does not require postprocedural oral anticoagulation. METHODS: Patients with atrial fibrillation at high stroke risk (CHA2DS2-VASc score ≥2) were recruited using standard selection criteria. The LAAC procedure was guided by transesophageal echocardiography with patients under general anesthesia. The CLAAS device is composed of a foam cup, with a Nitinol endoskeleton with an expanded polytetrafluoroethylene cover, delivered with a standard delivery system using a tether for full recapture. All patients received dual-antiplatelet therapy for 6 months, followed by aspirin alone. Transesophageal echocardiographic follow-up was scheduled for 45 days and 1 year. RESULTS: Twenty-two patients (63.7% with CHA2DS2-VASc scores ≥3, 76.2% with HAS-BLED scores ≥3) were enrolled. The device was successfully implanted in 18 patients and unsuccessfully in 4 patients. There were no serious procedural complications. On transesophageal echocardiography performed at 45 days, 1 significant leak (≥5 mm) was seen, which was due to a large posterior lobe not appreciated at the time of implantation, and 1 device-related thrombus was noted, which resolved on oral anticoagulation. There were no periprocedural strokes, major pericardial effusions, or systemic or device embolization. CONCLUSIONS: This first-in-human study demonstrates the clinical feasibility of the CLAAS device for LAAC.