RESUMEN
A 74-year-old man with a history of chronic lymphocytic leukemia (CLL) presented with large salmon-colored patch lesions along the inferior fornix and superotemporal conjunctiva of the OS. The patient underwent an incisional biopsy of the lesions, which showed a CLL with areas of large B-cell lymphoma, consistent with Richter transformation. Following medical and radiation-based therapy of these lesions, the patient returned 3 months later with inferomedial preseptal swelling in the contralateral eye, which biopsy proved to be recurrent/resistant low-grade CLL with a posttreatment extranodal marginal zone B-cell lymphoma pattern. This case exemplifies a rare presentation of CLL with Richter transformation and a recurrent/resistant posttreatment orbital CLL with a marginal zone B-cell lymphoma-like pattern.
RESUMEN
Primary aldosteronism PA is a secondary cause of hypertension that is often missed due to inadequate clinical evaluation and the lack of classically described laboratory abnormalities. Based on guidelines from the Endocrine Society, primary aldosteronism should be suspected in young patients with moderate to severe hypertension, patients with hypertension and coexisting hypokalemia, any patient with hypertension and an incidental adrenal adenoma, and hypertension in the setting of a significant family history of early onset hypertension or cerebral vascular accident in a first degree relative less than 40 years of age.1 In previous years, primary aldosteronism was attributed to less than one percent of all causes of secondary hypertension. However, recent research and increased utilization of aldosterone plasma renin ratio ARR as a method for screening has led to the understanding that majority of patients with PA are not hypokalemic, and the current literature now places the incidence of PA between 5-13 percent. Additionally, a growing body of evidence has demonstrated inflammatory, fibrotic, and remodeling effects on the cardiovascular and renal tissue that appear to be independent of PA- induced hypertension. Therefore a high suspicion for PA must be incorporated into evaluation of hypertensive patients, as diagnosis and subsequent treatment not only improves blood pressure control, but also acts to diminish cardiovascular morbidity and mortality. Here we present a case of a young woman with a seven-year history of hypertension prior to receiving a diagnosis of Conn's Syndrome.
Asunto(s)
Hiperaldosteronismo/diagnóstico , Hipertensión/etiología , Femenino , Humanos , Hiperaldosteronismo/complicaciones , Accidente Cerebrovascular , Adulto JovenAsunto(s)
Anemia Hemolítica/etiología , Oxigenación por Membrana Extracorpórea/efectos adversos , Síndrome de Dificultad Respiratoria/complicaciones , Sepsis/complicaciones , Estrés Fisiológico , Adolescente , Resultado Fatal , Humanos , Masculino , Síndrome de Dificultad Respiratoria/patología , Sepsis/sangre , Sepsis/patología , Estrés Fisiológico/fisiologíaRESUMEN
Emerging evidence suggests that the tumor suppressor p53 is also a crucial regulator for many physiological processes. Previous observations indicate that p53 suppresses inflammation by inhibiting inflammatory antigen-presenting cells. To investigate the potential role of p53 in autoimmune effector T cells, we generated p53(null)CD45.1 mice by crossing p53(null)CD45.2 and CD45.1 mice. We demonstrate that p53(null)CD45.1 mice spontaneously developed autoimmunity, with a significant increase in IL-17-producing Th17 effectors in their lymph nodes (4.7 ± 1.0%) compared to the age-matched counterparts (1.9 ± 0.8% for p53(null)CD45.2, 1.1 ± 0.2% for CD45.1, and 0.5 ± 0.1% for CD45.2 mice). Likewise, p53(null)CD45.1 mice possess highly elevated serum levels of inflammatory cytokines IL-17 and IL-6. This enhanced Th17 response results largely from an increased sensitivity of p53(null)CD45.1 T cells to IL-6-induced STAT3 phosphorylation. Administration of STAT3 inhibitor S31-201 (IC50 of 38.0 ± 7.2 µM for IL-6-induced STAT3 phosphorylation), but not PBS control, to p53(null)CD45.1 mice suppressed Th17 effectors and alleviated autoimmune pathology. This is the first report revealing that p53 activity in T cells suppresses autoimmunity by controlling Th17 effectors. This study suggests that p53 serves as a guardian of immunological functions and that the p53-STAT3-Th17 axis might be a therapeutic target for autoimmunity.
Asunto(s)
Autoinmunidad/inmunología , Interleucina-17/inmunología , Factor de Transcripción STAT3/inmunología , Proteína p53 Supresora de Tumor/inmunología , Animales , Western Blotting , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Citocinas/inmunología , Citocinas/metabolismo , Femenino , Citometría de Flujo , Interleucina-17/metabolismo , Interleucina-6/inmunología , Interleucina-6/metabolismo , Interleucina-6/farmacología , Antígenos Comunes de Leucocito/genética , Antígenos Comunes de Leucocito/inmunología , Antígenos Comunes de Leucocito/metabolismo , Tejido Linfoide/inmunología , Tejido Linfoide/metabolismo , Masculino , Ratones , Ratones Congénicos , Ratones Noqueados , FN-kappa B/inmunología , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/inmunología , Células TH1/inmunología , Células TH1/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
T-cell acute lymphoblastic leukemia (ALL) accounts for 15% of ALL cases in children and has been associated with a worse prognosis. Cytogenetic studies show an abnormal karyotype in 50-60% of the T-cell ALL patients; ABL1 fusions are present in approximately 8% of the cases. Dasatinib, a second-generation tyrosine kinase inhibitor, directly targets the BCR-ABL gene. We describe a pediatric case of T-cell ALL with amplification of the ABL1 gene in which remission was achieved only after the addition of dasatinib to conventional chemotherapy.
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Amplificación de Genes , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-abl/genética , Pirimidinas/uso terapéutico , Tiazoles/uso terapéutico , Niño , Dasatinib , Femenino , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Inducción de RemisiónRESUMEN
BACKGROUND: Monopolar cautery is the most commonly used surgical cutting and hemostatic tool for head and neck surgery. There are newer technologies that are being utilized with the goal of precise cutting, decreasing blood loss, reducing thermal damage, and allowing faster wound healing. Our study compares thermal damage caused by Harmonic scalpel and CO2 laser to cadaveric tongue. METHODS: Two fresh human cadaver heads were enrolled for the study. Oral tongue was exposed and incisions were made in the tongue akin to a tongue tumor resection using the harmonic scalpel and flexible C02 laser fiber at various settings recommended for surgery. The margins of resection were sampled, labeled, and sent for pathological analysis to assess depth of thermal damage calculated in millimeters. The pathologist was blinded to the surgical tool used. Control tongue tissue was also sent for comparison as a baseline for comparison. RESULTS: Three tongue samples were studied to assess depth of thermal damage by harmonic scalpel. The mean depth of thermal damage was 0.69 (range, 0.51 - 0.82). Five tongue samples were studied to assess depth of thermal damage by CO2 laser. The mean depth of thermal damage was 0.3 (range, 0.22 to 0.43). As expected, control samples showed 0 mm of thermal damage. There was a statistically significant difference between the depth of thermal injury to tongue resection margins by harmonic scalpel as compared to CO2 laser, (p = 0.003). CONCLUSION: In a cadaveric model, flexible CO2 laser fiber causes less depth of thermal damage when compared with harmonic scalpel at settings utilized in our study. However, the relevance of this information in terms of wound healing, hemostasis, safety, cost-effectiveness, and surgical outcomes needs to be further studied in clinical settings.
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Pérdida de Sangre Quirúrgica/prevención & control , Quemaduras/patología , Terapia por Láser/instrumentación , Láseres de Gas/uso terapéutico , Neoplasias de la Lengua/cirugía , Lengua/patología , Cicatrización de Heridas , Quemaduras/etiología , Cadáver , Diseño de Equipo , Humanos , Lengua/cirugíaRESUMEN
Budd Chiari syndrome is a rare disorder resulting from hepatic venous outflow tract obstruction anywhere from the small hepatic veins to the suprahepatic inferior vena cava. This patient has a hypercoagulable state secondary to heterozygous mutation of factor V and the JAK2 mutation and is being anticoagulated. We hypothesize that the low protein C and low antithrombin III levels seen in this patient resulted from decreased synthetic function of the liver and were not indicative of actual deficiencies. Indeed, reports of coexisting protein C and antithrombin III deficiencies are not existent in the literature and likely are not compatible with life. All patients with BCS warrant a hypercoagulable work up and JAK2 mutation is increasingly recognized as a contributing factor, even in those patients without obvious signs of polycythemia vera.
Asunto(s)
Anticoagulantes/uso terapéutico , Síndrome de Budd-Chiari/diagnóstico , Síndrome de Budd-Chiari/tratamiento farmacológico , Warfarina/uso terapéutico , Síndrome de Budd-Chiari/genética , Diagnóstico Diferencial , Femenino , Humanos , Tomografía Computarizada por Rayos X , Adulto JovenAsunto(s)
Trasplante de Médula Ósea , Encefalitis por Varicela Zóster/complicaciones , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Reacción Leucemoide/etiología , Meningoencefalitis/complicaciones , Encefalitis por Varicela Zóster/diagnóstico , Humanos , Reacción Leucemoide/líquido cefalorraquídeo , Masculino , Meningoencefalitis/diagnóstico , Persona de Mediana Edad , Trasplante HomólogoRESUMEN
Pathology training programs throughout the United States have endured unprecedented challenges dealing with the ongoing coronavirus disease 2019 pandemic. At Houston Methodist Hospital, the Department of Pathology and Genomic Medicine planned and executed a trainee-oriented, stepwise emergency response. The focus was on optimizing workflows among areas of both clinical and anatomic pathology, maintaining an excellent educational experience, and minimizing trainee exposure to coronavirus disease 2019. During the first phase of the response, trainees were divided into 2 groups: one working on-site and the other working remotely. With the progression of the pandemic, all trainees were called back on-site and further redeployed within our department to meet the significantly increased workload demands of our clinical laboratory services. Adjustments to trainee educational activities included, among others, the organization of a daily coronavirus disease 2019 virtual seminar series. This series served to facilitate communication between faculty, laboratory managers, and trainees. Moreover, it became a forum for trainees to provide updates on individual service workflows and volumes, ongoing projects and research, as well as literature reviews on coronavirus disease 2019-related topics. From our program's experience, redeploying pathology trainees within our department during the coronavirus disease 2019 pandemic resulted in optimization of patient care while ensuring trainee safety, and importantly, helped to maintain continuous high-quality education through active involvement in unique learning opportunities.
RESUMEN
Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) that has been shown to be a predictor of decreased atherosclerosis in the elderly and protective against atherosclerosis in mice. HCII inhibits thrombin in vitro and HCII-thrombin complexes have been detected in human plasma. Moreover, the mechanism of protection against atherosclerosis in mice was determined to be the inhibition of thrombin. Despite this evidence, the presence of HCII in human atherosclerotic tissue has not been reported. In this study, using samples of coronary arteries obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we explore the local relationship between HCII and (pro)thrombin in atherosclerosis. We found that HCII and (pro)thrombin are co-localized in the lipid-rich necrotic core of atheromas. A significant positive correlation between each protein and the severity of the atherosclerotic lesion was present. These results suggest that HCII is in a position to inhibit thrombin in atherosclerotic lesions where thrombin can exert a proatherogenic inflammatory response. However, these results should be tempered by the additional findings from this, and other studies, that indicate the presence of other plasma proteins (antithrombin, albumin, and alpha(1)-protease inhibitor) in the same localized region of the atheroma.
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Aterosclerosis/metabolismo , Vasos Coronarios/metabolismo , Cofactor II de Heparina/metabolismo , Protrombina/metabolismo , Adolescente , Adulto , Animales , Aterosclerosis/patología , Vasos Coronarios/patología , Cofactor II de Heparina/análisis , Humanos , Inmunohistoquímica , Ratones , Necrosis , Protrombina/análisis , Protrombina/antagonistas & inhibidores , Adulto JovenRESUMEN
Inflammatory pseudotumor (IPT) is a quasi-neoplastic lesion that most commonly involves the lung, but has been shown to occur in nearly every tissue type. Renal involvement is very uncommon. We report the second case of IPT ever published presenting as bilateral infiltrating renal masses. Although most renal IPTs were treated with nephrectomy, our patient was managed successfully with conservative steroid treatment, thereby avoiding the alternative of dialysis or kidney transplantation.
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Corticoesteroides/uso terapéutico , Granuloma de Células Plasmáticas/diagnóstico por imagen , Granuloma de Células Plasmáticas/tratamiento farmacológico , Riñón/diagnóstico por imagen , Corticoesteroides/farmacología , Adulto , Femenino , Humanos , Riñón/efectos de los fármacos , RadiografíaRESUMEN
Warthin's tumor is a benign lymphoepithelial neoplasm representing 10 per cent of all parotid gland tumors. Malignant transformation of a Warthin's tumor is an extremely rare event. We report a case of a patient with poorly differentiated carcinoma arising from a Warthin's tumor, as well as review the pathogenesis, histopathology, and surgical management of malignant Warthin's tumors.
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Adenolinfoma/patología , Neoplasias de la Parótida/patología , Adenolinfoma/diagnóstico , Adenolinfoma/cirugía , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias de la Parótida/diagnóstico , Neoplasias de la Parótida/cirugíaRESUMEN
OBJECTIVES: To characterize and quantitate hemoglobin (Hb) variants discovered during biometric hemoglobin A1c (HbA1c) analyses in a large multiethnic population with a focus on the effect of variants on testing method and results. METHODS: In total, 13,913 individuals had their HbA1c measured via ion-exchange high-performance liquid chromatography. Samples that had a variant Hb detected or HbF fraction more than 25% underwent variant Hb characterization and confirmation by gel electrophoresis. RBC indices were also evaluated for possible concomitant thalassemia. RESULTS: Of the 13,913 individuals evaluated, 524 (3.77%) had an Hb variant. The prevalence of each variant was as follows: HbS trait (n = 396, 2.85%), HbSS disease (n = 4, 0.03%), HbC trait (n = 85, 0.61%), HbCC disease (n = 2, 0.01%), HbSC disease (n = 5, 0.04%), HbE trait (n = 18, 0.13%), HbD or G trait (n = 9, 0.06%), HbS ß-thalassemia + disease (n = 1, 0.01%), hereditary persistence of HbF (n = 2, 0.01%), and HbMontgomery trait (n = 1, 0.01%). Concomitant α-thalassemia was detected in 20 (3.82%) of the 524 individuals with an Hb variant. CONCLUSIONS: This study represents one of the largest epidemiologic investigations into the prevalence of Hb variants in a North American metropolitan, multiethnic workforce and their dependents and reinforces the importance of method selection in populations with Hb variants.
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Hemoglobina Glucada/análisis , Talasemia alfa/epidemiología , Talasemia beta/epidemiología , Identificación Biométrica/métodos , Cromatografía Líquida de Alta Presión/métodos , Femenino , Pruebas Hematológicas/métodos , Humanos , Masculino , Prevalencia , Talasemia alfa/sangre , Talasemia alfa/etnología , Talasemia beta/sangre , Talasemia beta/etnologíaRESUMEN
The abscopal effect is the response to radiation at sites that are distant from the irradiated site of an organism, and it is thought to play a role in bone marrow (BM) recovery by initiating responses in the unirradiated bone marrow. Understanding the mechanism of this effect has applications in treating BM failure (BMF) and BM transplantation (BMT), and improving survival of nuclear disaster victims. Here, we investigated the use of multimodality imaging as a translational tool to longitudinally assess bone marrow recovery. We used positron emission tomography/computed tomography (PET/CT), magnetic resonance imaging (MRI) and optical imaging to quantify bone marrow activity, vascular response and marrow repopulation in fully and partially irradiated rodent models. We further measured the effects of radiation on serum cytokine levels, hematopoietic cell counts and histology. PET/CT imaging revealed a radiation-induced increase in proliferation in the shielded bone marrow (SBM) compared to exposed bone marrow (EBM) and sham controls. T2-weighted MRI showed radiation-induced hemorrhaging in the EBM and unirradiated SBM. In the EBM and SBM groups, we found alterations in serum cytokine and hormone levels and in hematopoietic cell population proportions, and histological evidence of osteoblast activation at the bone marrow interface. Importantly, we generated a BMT mouse model using fluorescent-labeled bone marrow donor cells and performed fluorescent imaging to reveal the migration of bone marrow cells from shielded to radioablated sites. Our study validates the use of multimodality imaging to monitor bone marrow recovery and provides evidence for the abscopal response in promoting bone marrow recovery after irradiation.
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Médula Ósea/diagnóstico por imagen , Médula Ósea/efectos de la radiación , Efecto Espectador/inmunología , Imagen Multimodal/métodos , Protección Radiológica/métodos , Animales , Médula Ósea/inmunología , Efecto Espectador/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Femenino , Masculino , Ratones , Dosificación Radioterapéutica , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To determine the associations among serum C-reactive protein (CRP) concentration, age, sex, risk factors for coronary heart disease (CHD), and atherosclerosis in young people. METHODS AND RESULTS: In 1244 subjects 15 to 34 years of age, we measured gross atherosclerotic lesions in the right coronary artery (RCA) and abdominal aorta (AA) and American Heart Association (AHA) lesion grade in the left anterior descending (LAD) coronary artery; serum CRP, lipoprotein cholesterol, and thiocyanate (for smoking) concentrations; intimal thickness of renal arteries (for hypertension); glycohemoglobin (for hyperglycemia); and body mass index (for obesity). Serum CRP levels increased with age, were higher in women than in men, and were positively related to obesity and hyperglycemia. Serum CRP > or =10 mg/L was associated with more extensive gross raised lesions in the RCA after age 25 and in the AA after age 30. Serum CRP > or =3 was associated with a greater prevalence of AHA grade 5 lesions in the proximal LAD coronary artery after age 25. The associations of CRP with lesions were independent of the traditional CHD risk factors. CONCLUSIONS: Serum CRP level is independently associated with advanced atherosclerosis in young persons.
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Aterosclerosis/sangre , Aterosclerosis/epidemiología , Proteína C-Reactiva/metabolismo , Enfermedad Coronaria/sangre , Enfermedad Coronaria/epidemiología , Adolescente , Adulto , Distribución por Edad , Aorta Abdominal/patología , Aterosclerosis/patología , Biomarcadores , Población Negra/estadística & datos numéricos , Enfermedad Coronaria/patología , Vasos Coronarios/patología , Femenino , Humanos , Masculino , Prevalencia , Factores de Riesgo , Fumar/epidemiología , Población Blanca/estadística & datos numéricosRESUMEN
BACKGROUND: Atherosclerosis begins in childhood and progresses through young adulthood to form the lesions that cause coronary heart disease. These preclinical lesions are associated with coronary heart disease risk factors in young persons. METHODS: The Pathobiological Determinants of Atherosclerosis in Youth study collected arteries and samples of blood and other tissues from persons aged 15 to 34 years who died of external causes and underwent autopsy in forensic laboratories. We measured the coronary heart disease risk factors and atherosclerotic lesions in the coronary arteries (CAs) (n = 1117) and the abdominal aorta (n = 1458). RESULTS: We developed risk scores, normalized so that a 1-unit increase was equivalent to a 1-year increase in age, to estimate the probability of advanced atherosclerotic lesions in the CAs and the abdominal aorta from age, sex, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia. Odds ratios for a 1-unit increase in the risk scores were 1.18 (95% confidence interval, 1.14-1.22) for the CAs and 1.29 (95% confidence interval, 1.23-1.35) for the abdominal aorta. These risk scores had good discrimination (c-indexes: 0.78 for the CAs and 0.84 for the abdominal aorta) and were calibrated. The presence of abdominal aortic lesions increased the likelihood of having CA lesions. CONCLUSION: Risk scores calculated from traditional coronary heart disease risk factors provide a tool for identifying young individuals with a high probability of having advanced atherosclerotic lesions.
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Aorta Abdominal/patología , Arteriosclerosis/patología , Vasos Coronarios/patología , Adolescente , Adulto , Arteriosclerosis/epidemiología , Cadáver , Causas de Muerte , Femenino , Humanos , Masculino , Oportunidad Relativa , Prevalencia , Pronóstico , Medición de Riesgo/métodos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Blacks have a high rate of sudden coronary death (SCD). We determined the rate of SCD in men and women 30 to 69 years of age in a 6-year period recorded at a state Medical Examiner's Office. METHODS AND RESULTS: In a subset of 327 whites and 130 blacks, hearts were systematically studied to determine the extent of coronary disease, presence and type of thrombus (acute rupture, acute erosion, stable plaque), and heart weight. These parameters were correlated with the presence of conventional risk factors. The estimated rate of SCD in blacks was similar to that in whites under the age of 40 years but increased compared with whites with advancing age, becoming 1.5 times the rate for whites in the 7th decade (95% of the increase in the 6th decade was due to sudden death with stable plaque). Among the autopsied group with severe coronary atherosclerosis, HDL cholesterol was higher and hypertension more prevalent in blacks, but there was no difference in the prevalence of healed infarcts, plaque burden, heart weight, acute thrombi, or rates of diabetes, cigarette smoking, and total cholesterol. CONCLUSIONS: When compared with a control autopsy group of 568 deaths, multivariate analysis showed a significant association in blacks between stable plaque and left ventricular hypertrophy (risk ratio, 7.6), type 1 diabetes (risk ratio, 3.6), hypertension (risk ratio, 3.5), elevated total cholesterol (risk ratio, 3.1) and type 2 diabetes (risk ratio, 2.9). Because these risk factors are associated with SCD in blacks, they may be important targets for reducing the disparately high rate of SCD in blacks as compared with whites.