RESUMO
Squamoid eccrine ductal carcinoma (SEDC) is a rare cutaneous neoplasm that often manifests as a plaque or nodule in sun-exposed areas of older patients. Herein, the authors report the first case of SEDC in the eyelid. A 76-year-old man presented with a 2.5 × 1.5 mm area of left upper eyelid erythema, thickening, ulceration, and scaling with madarosis superotemporally just above the lash line. Full-thickness wedge biopsy demonstrated irregular epithelial tubules with nuclear atypia and focal squamous differentiation, consistent with SEDC. The patient underwent Mohs resection and has had no recurrence approximately 27 months after surgical removal. The authors present this case to raise awareness of SEDC to ophthalmologists as all previous cases have been described in the nonophthalmic literature. A full-thickness biopsy is recommended to avoid misdiagnosing SEDC as squamous cell carcinoma (SCC), a less aggressive tumor. With greater awareness, there may be increased recognition of this likely underreported, more malignant entity.
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Adenocarcinoma de Células Claras , Neoplasias Ósseas , Neoplasias da Mama , Carcinoma Ductal , Carcinoma de Células Escamosas , Neoplasias Palpebrais , Neoplasias das Glândulas Sudoríparas , Idoso , Neoplasias Ósseas/patologia , Neoplasias da Mama/patologia , Carcinoma Ductal/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Glândulas Écrinas/patologia , Neoplasias Palpebrais/diagnóstico , Neoplasias Palpebrais/patologia , Neoplasias Palpebrais/cirurgia , Pálpebras/patologia , Humanos , Masculino , Neoplasias das Glândulas Sudoríparas/diagnóstico , Neoplasias das Glândulas Sudoríparas/patologia , Neoplasias das Glândulas Sudoríparas/cirurgiaRESUMO
Metastases of solid tumors to the eye and ocular adnexa are rare. Herein, the authors describe the clinical, histologic, and immunohistochemical findings of a patient with a history of adenocarcinoma of the colon and a uterine carcinosarcoma (malignant mixed Müllerian tumor) who presented with proptosis and decreased vision. Positive staining with PAX-8, p16 and negative reaction for CK20 and CDX2 helped to establish the uterine origin of the metastasis. This rare case demonstrates the utility of immunohistochemical probes, especially in patients with a complex oncological history, where multiple primary sources of the metastasis are in the differential diagnosis.
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Carcinossarcoma , Neoplasias Orbitárias , Neoplasias Uterinas , Biomarcadores Tumorais , Carcinossarcoma/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Órbita , Neoplasias Orbitárias/diagnóstico , Neoplasias Uterinas/diagnósticoRESUMO
BACKGROUND: Despite improvements in acute care and survival after non-ST-elevation acute coronary syndrome (NSTE-ACS) hospitalization, early readmissions remain common, and have significant clinical and financial impact. OBJECTIVES: Determine the predictors and etiologies of 30-day readmissions in NSTE-ACS. METHOD: The study cohort was derived from the National Readmission Database 2014 identifying patients with a primary diagnosis of NSTE-ACS using ICD9 code. RESULTS: We identified a total of 300,269 patients admitted with NSTE-ACS; 13.4% were readmitted within 30-day. The most common cause of readmission was heart failure (HF) (15.6%), followed by a recurrent myocardial infarction (MI) (10%). Predictors of increased readmissions were age ≥ 75 years (OR: 1.34, 95% CI: 1.30-1.39), female gender (OR 1.12, 95% CI 1.09-1.16), a Charlson Comorbidity Index (CCI) >3 (OR 2.11, 95% CI: 2.04-2.18), ESRD (OR 2.01, 95% CI 1.89-2.14), CKD (OR: 1.58, 95% CI: 1.51-1.64), length of stay ≥5 days (OR: 1.51, 95% CI 1.46-1.56) and adverse events during the index admission such as AKI (OR:1.31, 95% CI: 1.25-1.36), major bleeding (OR:1.20, 95% CI: 1.12-1.24); whereas admission to a teaching hospital (OR 0.92, 95% CI 0.89-0.95) and PCI (OR 0.70, 95% CI 0.67-0.72) were associated with less likelihood of 30-day readmission. CONCLUSION: Readmission rate at 30-days is high among NSTE-ACS patients and the most common readmission etiologies are HF and recurrent MI. A CCI more than 3 and ESRD were the most significant predictors for readmission; patients undergoing PCI had less odds of readmission.
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Síndrome Coronariana Aguda/terapia , Fármacos Cardiovasculares/uso terapêutico , Ponte de Artéria Coronária , Insuficiência Cardíaca/terapia , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Readmissão do Paciente , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Adolescente , Adulto , Idoso , Fármacos Cardiovasculares/efeitos adversos , Comorbidade , Bases de Dados Factuais , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Pulseless ventricular tachycardia/ventricular fibrillation (VT/VF) is the initial rhythm in a third of in-hospital cardiac arrest patients. Mechanical circulatory support (MCS) device use remains poorly understood in this population. METHODS: We conducted an observational analysis of temporal trends in the utilization of MCS in VT/VF IHCA between January 2008 and December 2014 utilizing the Nationwide Inpatient Sample (NIS) database. Using multivariable analysis, we assessed factors associated with MCS use and survival to discharge. RESULTS: Among 151,628 hospitalizations with VT/VF IHCA, 14,981 (9.9%) received MCS. Intra-aortic balloon pump (IABP) was the most commonly used MCS (9.1%). From 2008 to 2014, there was significant increase in the utilization of MCS (8.7-11%; ptrend < 0.0001). On multivariable analysis, there was 12-fold increase and three-fold increase in the utilization of PVAD and ECMO respectively; however, there was no significant change in the use of IABP. Over the seven-year sample period, there was significant increase in the overall survival to hospital discharge (35.4-43.5%; ptrend < 0.0001). Survival to hospital discharge increased in both MCS and non-MCS groups. CONCLUSION: There was significant increase in utilization of MCS after VT/VF IHCA during the study period. IABP was the most commonly utilized MCS. The survival to hospital discharge increased in the overall study population including both MCS and non-MCS groups. Future studies are needed to identify patient population most likely to benefit from the use of MCS after VT/VF IHCA.
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Oxigenação por Membrana Extracorpórea/tendências , Parada Cardíaca/terapia , Coração Auxiliar/tendências , Balão Intra-Aórtico/tendências , Oxigenadores de Membrana/tendências , Padrões de Prática Médica/tendências , Taquicardia Ventricular/complicações , Fibrilação Ventricular/complicações , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/instrumentação , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Parada Cardíaca/etiologia , Parada Cardíaca/mortalidade , Parada Cardíaca/fisiopatologia , Humanos , Balão Intra-Aórtico/efeitos adversos , Balão Intra-Aórtico/instrumentação , Balão Intra-Aórtico/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taquicardia Ventricular/mortalidade , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Fibrilação Ventricular/mortalidade , Fibrilação Ventricular/fisiopatologiaRESUMO
OBJECTIVE: The aim of our study was to study the impact of glycoprotein IIb/IIIa inhibitors (GPI) on in-hospital outcomes. BACKGROUND: There is paucity of data regarding the impact of GPI on the outcomes following peripheral endovascular interventions. METHODS: The study cohort was derived from Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database between the years 2006 and 2011. Peripheral endovascular interventions and GPI utilization were identified using appropriate ICD-9 Diagnostic and procedural codes. Two-level hierarchical multivariate mixed models were created. The study outcomes were: primary (in-hospital mortality and amputation studied separately) and secondary (composite of in-hospital mortality and postprocedural complications). Hospitalization costs were also assessed. RESULTS: GPI utilization (OR, 95% CI, P-value) was independently predictive of lower amputation rates (0.36, 0.27-0.49, <0.001). There was no significant difference in terms of in-hospital mortality (0.59, 0.31-1.14, P 0.117), although GPI use predicted worse secondary outcomes (1.23, 1.03-1.47, 0.023). Following propensity matching, the amputation rate was lower (3.2% vs. 8%, P < 0.001), while hospitalization costs were higher in the cohort that received GPI ($21,091 ± 404 vs. 19,407 ± 133, P < 0.001). CONCLUSIONS: Multivariate analysis revealed GPI use in peripheral endovascular interventions to be suggestive of an increase in composite end-point of in-hospital mortality and postprocedural complications, no impact on in-hospital mortality alone, significantly lower rate of amputation, and increase in hospitalization costs. © 2016 Wiley Periodicals, Inc.
Assuntos
Procedimentos Endovasculares , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Estudos Transversais , Bases de Dados Factuais , Custos de Medicamentos , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/economia , Procedimentos Endovasculares/mortalidade , Feminino , Custos Hospitalares , Mortalidade Hospitalar , Humanos , Salvamento de Membro , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/economia , Doença Arterial Periférica/mortalidade , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/economia , Pontuação de Propensão , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
PURPOSE: To examine the impact of intravascular ultrasound (IVUS) utilization during lower limb endovascular interventions as regards postprocedural complications and amputation. METHODS: The study cohort was derived from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database between the years 2006 and 2011. Peripheral endovascular interventions were identified using appropriate ICD-9 procedure codes. Two-level hierarchical multivariate mixed models were created. The co-primary outcomes were in-hospital mortality and amputation; the secondary outcome was postprocedural complications. Model results are given as the odds ratio (OR) and 95% confidence interval (CI). Hospitalization costs were also assessed. RESULTS: Overall, among the 92,714 patients extracted from the database during the observation period, IVUS was used in 1299 (1.4%) patients. IVUS utilization during lower extremity peripheral vascular procedures was independently predictive of a lower rate of postprocedural complications (OR 0.80, 95% CI 0.66 to 0.99, p=0.037) as well as lower amputation rates (OR 0.59, 95% CI 0.45 to 0.77, p<0.001) without any significant impact on in-hospital mortality. Multivariate analysis also revealed IVUS utilization to be predictive of a nonsignificant increase in hospitalization costs ($1333, 95% CI -$167 to +$2833, p=0.082). CONCLUSION: IVUS use during lower limb endovascular interventions is predictive of lower postprocedural complication and amputation rates with a nonsignificant increase in hospitalization costs.
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Procedimentos Endovasculares/estatística & dados numéricos , Extremidade Inferior/irrigação sanguínea , Doenças Vasculares Periféricas/terapia , Padrões de Prática Médica , Ultrassonografia de Intervenção/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Distribuição de Qui-Quadrado , Análise Custo-Benefício , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/economia , Procedimentos Endovasculares/mortalidade , Feminino , Custos Hospitalares , Mortalidade Hospitalar , Humanos , Salvamento de Membro , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Doenças Vasculares Periféricas/diagnóstico por imagem , Doenças Vasculares Periféricas/mortalidade , Doenças Vasculares Periféricas/cirurgia , Padrões de Prática Médica/economia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia de Intervenção/economia , Estados Unidos , Adulto JovemRESUMO
Prolyl hydroxylation is a PTM that plays an important role in the formation of collagen fibrils and in the oxygen-dependent regulation of hypoxia inducible factor-α (HIF-α). While this modification has been well characterized in the context of these proteins, it remains unclear to what extent it occurs in the remaining mammalian proteome. We explored this question using MS to analyze cellular extracts subjected to various fractionation strategies. In one strategy, we employed the von Hippel Lindau tumor suppressor protein, which recognizes prolyl hydroxylated HIF-α, as a scaffold for generating hydroxyproline capture reagents. We report novel sites of prolyl hydroxylation within five proteins: FK506-binding protein 10, myosin heavy chain 10, hexokinase 2, pyruvate kinase, and C-1 Tetrahydrofolate synthase. Furthermore, we show that identification of prolyl hydroxylation presents a significant technical challenge owing to widespread isobaric methionine oxidation, and that manual inspection of spectra of modified peptides in this context is critical for validation.
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Processamento de Proteína Pós-Traducional , Proteoma/metabolismo , Sequência de Aminoácidos , Cromatografia em Gel , Células HeLa , Humanos , Hidroxilação , Anotação de Sequência Molecular , Prolina/química , Proteoma/química , Proteoma/isolamento & purificação , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: The aim of the study was to assess the utilization of catheter-directed thrombolysis (CDT) and its comparative effectiveness against systemic thrombolysis in acute pulmonary embolism (PE). BACKGROUND: Contemporary real world data regarding utilization and outcomes comparing systemic thrombolysis with CDT for PE is sparse. METHODS: We queried the Nationwide Inpatient Sample from 2010 to 2012 using the ICD-9-CM diagnosis code 415.11, 415.13, and 415.19 for acute PE. We used propensity score analysis to compare outcomes between systemic thrombolysis and CDT. Primary outcome was in-hospital mortality. Secondary outcome was combined in-hospital mortality and intracranial hemorrhage (ICH). RESULTS: Out of 110,731 patients hospitalized with PE, we identified 1,521 patients treated with thrombolysis, of which 1,169 patients received systemic thrombolysis and 352 patients received CDT. After propensity-matched comparison, primary and secondary outcomes were significantly lower in the CDT group compared to systemic thrombolysis (21.81% vs. 13.36%, OR 0.55, 95% CI 0.36-0.85, P value = 0.007) and (22.89% vs. 13.36%, OR 0.52, 95% CI 0.34-0.80, P value = 0.003), respectively. The median length of stay [7 days, interquartile range (IQR) (5-9 days) vs. 7 days, IQR (5-10 days), P = 0.17] was not significant between the two groups. The CDT group had higher cost of hospitalization [$17,218, IQR ($12,272-$23,906) vs. $23,799, IQR ($17,892-$35,338), P < 0.001]. Multivariate analysis identified increasing age, saddle PE, cardiopulmonary arrest, and Medicaid insurance as independent predictors of in-hospital mortality. CONCLUSIONS: CDT was associated with lower in-hospital mortality and combined in-hospital mortality and ICH.
Assuntos
Cateterismo de Swan-Ganz , Fibrinolíticos/administração & dosagem , Padrões de Prática Médica , Embolia Pulmonar/tratamento farmacológico , Terapia Trombolítica/métodos , Adulto , Idoso , Cateterismo de Swan-Ganz/efeitos adversos , Cateterismo de Swan-Ganz/mortalidade , Cateterismo de Swan-Ganz/estatística & dados numéricos , Cateterismo de Swan-Ganz/tendências , Distribuição de Qui-Quadrado , Bases de Dados Factuais , Feminino , Fibrinolíticos/efeitos adversos , Mortalidade Hospitalar , Humanos , Hemorragias Intracranianas/induzido quimicamente , Modelos Logísticos , Masculino , Medicaid , Medicare , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Padrões de Prática Médica/tendências , Pontuação de Propensão , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Fatores de Risco , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Terapia Trombolítica/estatística & dados numéricos , Terapia Trombolítica/tendências , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
Paclitaxel has emerged as a front line treatment for aggressive malignancies of the breast, lung, and ovary. Successful therapy of cancer is frequently undermined by the development of paclitaxel resistance. There is a growing need to find other therapeutic targets to facilitate treatment of drug-resistant cancers. Using a proteomics approach, elevated levels of Prohibitin1 (PHB1) and GSTpi were found associated with paclitaxel resistance in discrete subcellular fractions of two drug-resistant sublines relative to their sensitive sublines. Immunofluorescence staining and fractionation studies revealed increased levels of PHB1 on the surface of resistant cell lines. Transiently silencing either PHB1 or GSTpi gene expression using siRNA in the paclitaxel-resistant cancer cell sublines partially sensitized these cells toward paclitaxel. Intriguingly, silencing PHB1 but not GSTpi resulted in activation of the intrinsic apoptosis pathway in response to paclitaxel. Similarly, stably silencing either PHB1 or GSTpi significantly improved paclitaxel sensitivity in A549TR cells both in vitro and in vivo. Our results indicate that PHB1 is a mediator of paclitaxel resistance and that this resistance may depend on the cellular localization of the protein. We suggest PHB1 as a potential target for therapeutic strategies for the treatment of drug-resistant tumors.
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Resistencia a Medicamentos Antineoplásicos , Neoplasias/tratamento farmacológico , Paclitaxel/farmacologia , Proteínas Repressoras/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Humanos , Immunoblotting , Masculino , Camundongos , Camundongos Nus , Microscopia Confocal , Mitocôndrias/metabolismo , Neoplasias/genética , Neoplasias/patologia , Proibitinas , Proteômica/métodos , Interferência de RNA , Proteínas Repressoras/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: To describe a case of chronic pediatric retinal detachment with multiple macrocysts, its surgical management, and a review of the literature. METHODS: Case report with fundus photography and optical coherence tomography. RESULTS: We describe a case of an asymptomatic, 11-year-old boy with a chronic rhegmatogenous retinal detachment with multiple peripheral macrocysts. The patient had counting fingers visual acuity on presentation. The detachment was successfully surgically repaired with scleral buckling, subretinal fluid drainage, cryotherapy, and a SF6 tamponade. At the 12-month follow-up, the retina remained attached with improvement of visual acuity to 20/100 with resolution of the cysts. Optical coherence tomography revealed loss of macular ellipsoid zone. Genetic testing revealed a heterozygous dominant COL11A1 mutation. CONCLUSION: To the authors' knowledge, this is the first reported case of chronic retinal detachment presenting with multiple peripheral macrocysts in a pediatric patient with Stickler syndrome. More research is needed into the cause and significance of retinal macrocysts, particularly in the pediatric population.
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Descolamento Retiniano , Masculino , Humanos , Criança , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/cirurgia , Recurvamento da Esclera/métodos , Retina , Acuidade Visual , Crioterapia , Vitrectomia/métodos , Tomografia de Coerência Óptica/métodosRESUMO
BACKGROUND: Scleral buckling has been the standard for rhegmatogenous retinal detachment repair in young patients given the typical lack of posterior vitreous detachment, phakic status, and lower risk of proliferative vitreoretinopathy. In older patients, pars plana vitrectomy alone is typically used for rhegmatogenous retinal detachment repair. We report the outcomes and complications of pars plana vitrectomy for rhegmatogenous retinal detachment in young eyes. METHODS: Retrospective, single-center cohort study. Medical records of patients between 15 to 45 years of age undergoing primary pars plana vitrectomy for rhegmatogenous retinal detachment repair between 2010 and 2020 were carefully reviewed. All analyses were performed using the Kruskal-Wallis tests for numeric covariates between age groups. RESULTS: Eyes were stratified by age: 15-24 (group 1, n = 10), 25-34 (group 2, n = 14), and 35-45 (group 3, n = 38). The average number of surgeries were 1.9, 1.4, and 1.1 in groups 1, 2, and 3, respectively (p = 0.004). Single surgery success rates were 50%, 64%, and 92% in groups 1, 2 and 3, respectively (p = 0.005). Final reattachment rates were 80%, 93%, 100% in groups 1, 2, and 3, respectively (p = 0.568). Proliferative vitreoretinopathy developed in 50%, 7%, and 8% of eyes in groups 1, 2, and 3, respectively (p < 0.001). CONCLUSION: While the final reattachment rates were excellent in all groups, the higher rates of proliferative vitreoretinopathy and lower single surgery success rate in younger patients may suggest that primary pars plana vitrectomy may not be the optimal repair method in these age groups.
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While multiplexing samples using DNA barcoding revolutionized the pace of biomedical discovery, multiplexing of live imaging-based applications has been limited by the number of fluorescent proteins that can be deconvoluted using common microscopy equipment. To address this limitation, we develop visual barcodes that discriminate the clonal identity of single cells by different fluorescent proteins that are targeted to specific subcellular locations. We demonstrate that deconvolution of these barcodes is highly accurate and robust to many cellular perturbations. We then use visual barcodes to generate 'Signalome' cell-lines by mixing 12 clones of different live reporters into a single population, allowing simultaneous monitoring of the activity in 12 branches of signaling, at clonal resolution, over time. Using the 'Signalome' we identify two distinct clusters of signaling pathways that balance growth and proliferation, emphasizing the importance of growth homeostasis as a central organizing principle in cancer signaling. The ability to multiplex samples in live imaging applications, both in vitro and in vivo may allow better high-content characterization of complex biological systems.
Assuntos
DNA , Microscopia , Células Clonais , Código de Barras de DNA Taxonômico/métodosRESUMO
While molecules that promote the growth of animal cells have been identified, it remains unclear how such signals are orchestrated to determine a characteristic target size for different cell types. It is increasingly clear that cell size is determined by size checkpoints-mechanisms that restrict the cell cycle progression of cells that are smaller than their target size. Previously, we described a p38 MAPK-dependent cell size checkpoint mechanism whereby p38 is selectively activated and prevents cell cycle progression in cells that are smaller than a given target size. In this study, we show that the specific target size required for inactivation of p38 and transition through the cell cycle is determined by CDK4 activity. Our data suggest a model whereby p38 and CDK4 cooperate analogously to the function of a thermostat: while p38 senses irregularities in size, CDK4 corresponds to the thermostat dial that sets the target size.
Assuntos
Ciclo Celular/genética , Tamanho Celular , Quinase 4 Dependente de Ciclina/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Homeostase/genética , Humanos , Sistema de Sinalização das MAP Quinases/genéticaRESUMO
PURPOSE: To describe the clinical and pathologic characteristics of a case of retinal vasculitis and vitritis following brolucizumab administration and subsequent ranibizumab treatment. OBSERVATIONS: A 76-year old Caucasian woman experienced pain, decreased vision and floaters one week after receiving her third monthly intravitreal brolucizumab injection in the right eye for exudative age-related macular degeneration. Examination was significant for 0.5+ anterior chamber cells, vitritis, mild peripheral vascular sheathing, and decreased vision from 20/70 to 20/200. She was started on topical 1% prednisolone acetate with improvement in her examination. She was switched to ranibizumab one month after her last brolucizumab injection of the right eye. Three weeks after her ranibizumab injection, she noticed photophobia, pain and decreased vision. Examination revealed worsening uveitis, vitritis, vascular sheathing, and decreased vision to count fingers. Despite starting on 0.05% difluprednate drops every 2 hours and oral high-dose methylprednisolone, the patient did not have any significant improvement in her symptoms or examination. She underwent pars plana vitrectomy and vitreous biopsy with intravitreal triamcinolone injection to the right eye. Vitreous biopsy and culture ruled out infectious endophthalmitis, and further cytopathologic analysis revealed chronic inflammatory infiltrate. CONCLUSION AND IMPORTANCE: Treatment with brolucizumab can result in intraocular inflammation and retinal vasculitis likely due to a delayed hypersensitivity reaction to the drug, supported by cytopathologic analysis of a vitreous sample. We demonstrate a case where retreatment with an alternative anti-VEGF agent resulted in worsening vision and vasculitis.
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Purpose: Intravitreal injection therapy (IVT) is the most performed procedure in ophthalmology. This study was conducted to determine current trends in IVT delivery. Methods: An online, 31-question, multiple-choice survey was sent to 1677 retina specialists. The survey consisted of 3 sections: general questions, procedure technique, and postprocedure technique. Results: A total of 264 (16%) retina specialists completed the survey. The use of povidone-iodine (100%) and small-gauge needles (97%) was common, whereas ocular anesthesia was split among lidocaine gel (31%), lidocaine drops (25%), subconjunctival lidocaine (28%), and lidocaine-soaked pledgets (15%). More than 85% indicated povidone-iodine contributes to post-IVT corneal toxicity, and 12% reported that a needlestick injury to physician or staff occurred during IVT. Conclusions: Key areas for IVT improvement include optimized ocular anesthesia, development of a guarded needle for ocular drug delivery, and formulation of a less toxic ocular antiseptic.
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Importance: The number of older adults with visual impairment (VI) and dementia is projected to increase in the US because of the aging of the population. Dementia and VI commonly co-occur and are each independently associated with disability. To care for an aging population, it may be important to characterize the association of coexisting dementia and self-reported VI on daily functioning. Objective: To evaluate the association of co-occurring dementia and self-reported VI on daily functioning. Design, Setting, and Participants: This cross-sectional analysis of a nationally representative cohort study used data from the National Health and Aging Trends Study (NHATS), an annual study of US adults 65 years and older. Participants in the 2015 survey with complete data on outcomes, associated factors, and covariates were included in this study. Data analysis took place from January 2019 to November 2019. Main Outcomes and Measures: Multivariable Poisson regression was used to model the independent associations and interaction of dementia and self-reported VI status on 3 functional activity scales (self-care, mobility, and household activities). Marginal predicted proportions were calculated. Analyses were adjusted for sociodemographic and medical factors and accounted for the complex survey design. Results: A total of 7124 participants were included. The weighted proportion of female respondents was 55.3% (95% CI, 54.0%-56.6%), and 56.1% (95% CI, 54.1%-58.1%) were between 65 and 74 years old. Self-reported VI was present in 8.6% (95% CI, 7.8%-9.3%) of participants, while 8.3% (95% CI, 7.8%-8.9%) had possible dementia and 6.3% (95% CI, 5.7%-6.9%) had probable dementia. Self-reported VI was associated with an expected decrease in mobility score of 14.7% (functional scale scores: no VI, 10.82 vs VI, 9.23), self-care score of 9.5% (no VI, 14.54 vs VI, 13.16), and household activity score of 15.2% (no VI, 18.23 vs VI, 15.45), while probable dementia was associated with expected decreases of 27.8% (no dementia, 10.82 vs probable dementia, 7.81), 22.9% (no dementia, 14.54 vs probable dementia, 11.20), and 34.7% (no dementia, 18.23 vs probable dementia, 11.90), respectively. Among those with probable dementia and self-reported VI, there was an expected decrease in mobility score of 50.1% (functional ability scores: no VI and no dementia, 10.82 vs VI and probable dementia, 5.40), self-care score of 42.4% (no VI and no dementia, 14.54 vs VI and probable dementia, 8.38), and household activity score of 52.4% (no VI and no dementia, 18.23 vs VI and probable dementia, 8.68), suggesting that respondents with co-occurring dementia and self-reported VI had lower functional activity scores than would be associated with the independent contributions of these conditions. Conclusions and Relevance: Older adults with both dementia and self-reported VI may be at high risk for disability, and their co-occurrence may potentiate this risk. These findings suggest that the growing population of older adults with both visual impairment and dementia may benefit from interventions to maximize vision and cognition and promote functioning and independence.
Assuntos
Atividades Cotidianas , Envelhecimento , Demência/epidemiologia , Autorrelato , Baixa Visão/epidemiologia , Acuidade Visual , Idoso , Comorbidade , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Estados Unidos/epidemiologia , Baixa Visão/fisiopatologiaRESUMO
Phage-displayed synthetic antibody (Ab) repertoires have become a major source of affinity reagents for basic and clinical research. Specific Abs identified from such libraries are often screened as fragments antigen binding (Fabs) produced in bacteria, and those with desired biochemical characteristics are reformatted for production as full-length immunoglobulin G (IgG) in mammalian cells. The conversion of Fabs to IgGs is a cumbersome and often rate-limiting step in the development of Abs. Moreover, biochemical properties required for lead IgG development are not always shared by the Fabs, and these issues are not uncovered until a significant effort has been spent on Abs that ultimately will not be useful. Thus, there is a need for simple and rapid techniques to convert phage-displayed Fabs to IgGs at an early stage of the Ab screening process. We report the generation of a highly diverse phage-displayed synthetic single-chain Fab (scFab) library, in which the light and heavy chains were tethered with an optimized linker. Following selection, pools of scFabs were converted to single-chain IgGs (scIgGs) en masse, enabling facile screening of hundreds of phage-derived scIgGs. We show that this approach can be used to rapidly screen for and select scIgGs that target cell-surface receptors, and scIgGs behave the same as conventional IgGs.
Assuntos
Técnicas de Visualização da Superfície Celular , Biblioteca Gênica , Fragmentos Fab das Imunoglobulinas , Imunoglobulina G , Anticorpos de Cadeia Única , Humanos , Fragmentos Fab das Imunoglobulinas/biossíntese , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/genética , Imunoglobulina G/biossíntese , Imunoglobulina G/química , Imunoglobulina G/genética , Anticorpos de Cadeia Única/biossíntese , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/genéticaRESUMO
The authors report a case of a synthetic fiber granuloma to demonstrate the challenges in diagnosing these lesions and to highlight their histopathologic features. This is the first report in the literature to use histopatho-logic and immunofluorescence studies to characterize the subtype and distribution of macrophages in synthetic fiber granuloma. [J Pediatr Ophthalmol Strabismus. 2020;57:e92-e95.].
Assuntos
Túnica Conjuntiva/patologia , Doenças da Túnica Conjuntiva/diagnóstico , Granuloma/diagnóstico , Biópsia , Criança , Diagnóstico Diferencial , Humanos , MasculinoRESUMO
INTRODUCTION: Intravascular imaging-guided percutaneous coronary intervention (PCI) has shown to improve outcomes in randomized controlled trials. However, there are little real-world data about intravascular imaging utilization during PCI and its outcomes in the United States. METHODS: We conducted an observational analysis on the use of intravascular imaging (Intravascular Ultrasound or Optical Coherence Tomography)-guided PCI in 2,425,036 patients undergoing PCI between January 2010 and December 2014 from the Nationwide Inpatient Sample database. Utilizing propensity score matching, 83,988 matched pairs were identified. The primary outcome was in-hospital mortality. The secondary outcomes included cardiogenic shock and acute kidney injury. RESULTS: Among the 2,425,036 patients, 161,808 (6.7%) underwent imaging-guided PCI. Use of imaging-guidance increased from 6% in 2010 to 6.6% in 2014 (Ptrend < 0.001). The in-hospital mortality was significantly different between imaging-guided PCI and angiography-guided PCI [1.0% vs. 1.5%; adjusted OR: 0.67; 95% confidence interval (CI): 0.54-0.83, P < 0.001]. The rates of cardiogenic shock (2.5% vs. 3.1%; adjusted OR: 0.78; 95% CI: 0.66-0.93; P = 0.005) were significantly lower in imaging-guided PCI group and acute kidney injury rates (7.0% vs. 7.1%; adjusted OR: 0.99; 95% CI: 0.89-1.12; P = 0.919) were not significantly different. CONCLUSIONS: Imaging-guided PCI is associated with lower in-hospital mortality. Yet, a small proportion of patients undergoing PCI have imaging-guidance.