RESUMEN
B cells and their immunoglobulin products participate in allograft rejection of transplanted human kidneys in which an interesting feature is the presence of a germinal center like B-cell clusters in the allograft. We report here that the immunoglobulin repertoires of these infiltrating B cells are highly restricted and the B cells within a cluster are clonal. Antibody libraries made from the infiltrating B cells of individual patients unexpectedly revealed that each patient utilizes a particular set of dominant germ line genes as well as dominant complementarity determining region 3. Comparison of kidney and peripheral blood from the same patient showed that the immunoglobulin genes from both compartments had dominant clones, but they differed. The lymphocytes that infiltrate the kidneys express the immunoglobulin gene somatic recombination machinery usually restricted to highly activated lymphocytes in germinal centers and lymphomas. An analogy can be made between the inescapable antigenic drive in chronic infection versus that in an allograft, both of which may lead to emergence of dominant B-cell clones and even lymphoid malignancy.
Asunto(s)
Linfocitos B/citología , Regulación de la Expresión Génica/inmunología , Rechazo de Injerto/inmunología , Trasplante de Riñón , Riñón/citología , Secuencia de Aminoácidos , Anticuerpos/genética , Anticuerpos/inmunología , Linfocitos B/inmunología , Secuencia de Bases , Movimiento Celular/inmunología , Células Clonales/inmunología , Regiones Determinantes de Complementariedad/genética , Genes de Inmunoglobulinas/inmunología , Humanos , Hibridación in Situ , Riñón/inmunología , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADNRESUMEN
AIM: This study investigated the humoral response against SARS-CoV-2 in patients needing intensive care unit (ICU) care compared with those on general medicine wards. MATERIALS & METHODS: The authors retrospectively reviewed 113 hospitalized patients with COVID-19. They assessed antibody response against five SARS-CoV-2 epitopes at 6-14 days post symptom onset in these patients. RESULTS: Patients with ICU admissions had decreased anti-nucleocapsid immunoglobulin (Ig)M and increased anti-spike IgG compared with patients not requiring the ICU. IgG levels were positively correlated with length of stay. CONCLUSION: Higher levels of IgG against the spike protein correlate with COVID-19 disease severity and length of stay in hospitalized patients. This adds to the knowledge of biochemical response to clinical disease and may help predict ICU needs.
RESUMEN
Although interest in the role of donor-specific antibodies (DSAs) in kidney transplant rejection, graft survival, and histopathological outcomes is increasing, their impact on steroid avoidance or minimization in renal transplant populations is poorly understood. Primary outcomes of graft survival, rejection, and histopathological findings were assessed in 188 patients who received transplants between 2012 and 2015 at the Scripps Center for Organ Transplantation, which follows a steroid avoidance protocol. Analyses were performed using data from the United Network for Organ Sharing. Cohorts included kidney transplant recipients with de novo DSAs (dnDSAs; n = 27), preformed DSAs (pfDSAs; n = 15), and no DSAs (nDSAs; n = 146). Median time to dnDSA development (classes I and II) was shorter (102 days) than in previous studies. Rejection of any type was associated with DSAs to class I HLA (P < .05) and class II HLA (P < .01) but not with graft loss. Although mean fluorescence intensity (MFI) independently showed no association with rejection, an MFI >5000 showed a trend toward more antibody-mediated rejection (P < .06), though graft loss was not independently associated. Banff chronic allograft nephropathy scores and a modified chronic injury score were increased in the dnDSA cohort at 6 months, but not at 2 years (P < .001 and P < .08, respectively). Our data suggest that dnDSAs and pfDSAs impact short-term rejection rates but do not negatively impact graft survival or histopathological outcomes at 2 years. Periodic protocol post-transplant DSA monitoring may preemptively identify patients who develop dnDSAs who are at a higher risk for rejection.
Asunto(s)
Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Terapia de Inmunosupresión/métodos , Isoanticuerpos/inmunología , Trasplante de Riñón , Adulto , Estudios de Cohortes , Femenino , Antígenos HLA/inmunología , Humanos , Trasplante de Riñón/métodos , Masculino , Persona de Mediana Edad , Esteroides , Receptores de TrasplantesRESUMEN
BACKGROUND: Rapid diagnostics for bloodstream infections have been shown to improve outcomes. Most studies have focused on rapid diagnostics for a single pathogen and have been conducted in academic medical centers. The Verigene Gram-Positive Blood Culture Test (BC-GP) identifies 12 gram-positive organisms and 3 genetic markers of antibiotic resistance from positive blood culture media in 2.5 hours. This study evaluates implementation of the Verigene BC-GP panel in combination with real-time support from the Antibiotic Stewardship Team (AST) in a community hospital system. METHODS: This multicenter, pre-post, quasi-experimental study was conducted at the five hospitals that compose Scripps Healthcare. Rapid diagnostic testing was performed at a central laboratory from 7 a.m.-7 p.m. Pharmacists notified physicians of results and assisted with antibiotic modifications. The primary outcomes were average time to targeted antibiotic therapy and difference in antibiotic duration for contaminants. Secondary end points included hospital length of stay, mortality, pharmacy costs, and overall hospitalization costs. Adult patients with a gram-positive bacteremia admitted in 2011 (pre-rapid testing) were compared with those admitted in 2014 (post-rapid testing). RESULTS: There were 103 patients in the preintervention group and 64 patients in the intervention group. The optimized identification process, combined with AST intervention, improved mean time to targeted antibiotic therapy (61.1 vs 35.4 hrs, p<0.001) and decreased mean duration of antibiotic therapy for blood culture contaminants (42.3 vs 24.5 hrs, p=0.03). Median length of stay (9.1 vs 7.2 days, p=0.04) and overall median hospitalization costs ($17,530 vs $10,290, p=0.04) were lower in the intervention group. Mortality was similar between groups (9.1% vs 9.2%, p=0.98). CONCLUSION: Rapid identification of gram-positive blood cultures with AST intervention decreased time to targeted antibiotic therapy, length of unnecessary antibiotic therapy for blood culture contaminants, length of stay, and overall hospital costs.
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Antibacterianos/administración & dosificación , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Hospitales Comunitarios , Anciano , Anciano de 80 o más Años , Diagnóstico Precoz , Femenino , Hospitalización/tendencias , Hospitales Comunitarios/tendencias , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del TratamientoRESUMEN
After excluding the typical causes, the underlying etiology of severe acute pancreatitis is often elusive; tumors are on the differential but may be difficult to prove in the absence of a discrete mass on imaging. In this report, we describe the case of an elderly woman with diffuse large B-cell lymphoma masquerading as acute pancreatitis. To our knowledge, only twelve other cases of pancreatic B-cell lymphoma presenting as acute pancreatitis have been described. However, while other cases involved well-circumscribed tumors of the pancreas, this is the first known case of pancreatic lymphoma of a diffusely infiltrating pattern presenting as acute pancreatitis.
Asunto(s)
Fascitis Necrotizante/diagnóstico , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Lesión Renal Aguda/etiología , Amputación Quirúrgica , Diabetes Mellitus Tipo 2/complicaciones , Susceptibilidad a Enfermedades , Fascitis Necrotizante/complicaciones , Fascitis Necrotizante/diagnóstico por imagen , Fascitis Necrotizante/patología , Fascitis Necrotizante/cirugía , Fibroblastos/patología , Humanos , Masculino , Persona de Mediana Edad , MusloRESUMEN
Medullary carcinoma of the thyroid requires aggressive treatment because of its potential to metastasize and because of the current limitations of preoperative localization and systemic therapy. If these tumors could be made to fluoresce in vivo with tagged fluorophore antibodies against tumor antigens, surgeons would be able to obtain additional information in the operating room to facilitate a more complete resection. Based on the success of our previous work in breast and colon cancer models, we conducted an animal study of in vivo tumor fluorescence of a human medullary thyroid cell line in which bright tumor fluorescence is visible during dissection. To accomplish this, we used an inexpensive and commercially available handheld, blue (470 nm), light-emitting diode flashlight and filtered goggles (520 nm). This procedure, which we call the fluorescent antibody-assisted surgical technique (FAAST), is easy to perform, requires no complex or expensive technical equipment, and has the potential to be applied to a wide variety of tumors. To the best of our knowledge, this is the first experiment of its kind to be reported in the literature.
Asunto(s)
Carcinoma Medular/diagnóstico , Técnica del Anticuerpo Fluorescente/instrumentación , Neoplasias de la Tiroides/diagnóstico , Animales , Carcinoma Medular/patología , Carcinoma Medular/cirugía , Ratones , Proyectos Piloto , Pronóstico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugíaRESUMEN
BACKGROUND: : Primitive peripheral neuroectodermal tumors (PNETs) of the uterus are rare. Recent data have demonstrated improved response rates with adjuvant chemotherapy. CASE: : A 26-year-old, gravida 2, para 1, Filipina female underwent an emergent cesarean section for fetal indications. Intraoperative findings were remarkable for a soft tissue mass in the lower uterine segment. Histologic features, immunohistochemical findings, and chromosomal analysis were consistent with a PNET. The patient underwent radical surgery, adjuvant chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VAC/IE), and whole pelvic radiation therapy. CONCLUSION: : Only 14 case reports of primitive neuroectodermal tumors of the uterus have been published in the English literature to date. No definitive conclusions concerning the therapeutic management and prognosis have been ascertained.
Asunto(s)
Tumores Neuroectodérmicos Periféricos Primitivos/diagnóstico , Tumores Neuroectodérmicos Periféricos Primitivos/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapia , Adulto , Femenino , Humanos , Embarazo , Complicaciones Neoplásicas del Embarazo/diagnósticoRESUMEN
Hairy cell leukemia (HCL) is a rare chronic B-cell lymphoproliferative disorder characterized by splenomegaly, pancytopenia, and circulating atypical lymphocytes with circumferential cytoplasmic projections. Although uncommon, HCL cases refractory to standard therapy occur, and effective alternatives are limited. There is evolving literature supporting monoclonal antibody therapy in the treatment of B-cell lymphoid malignancies, including anti-CD52 (Campath-1H, alemtuzumab). We have examined nine cases of HCL and one case of HCL variant by flow cytometry for CD52 expression. All cases expressed CD52 antigen in 92-100% of the malignant cells. The demonstration of CD52 antigen expression on HCL cells provides the rationale for the use of alemtuzumab in refractory HCL.
Asunto(s)
Antígenos CD/análisis , Antígenos de Neoplasias/análisis , Glicoproteínas/análisis , Leucemia de Células Pilosas/patología , Adulto , Anciano , Alemtuzumab , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Anticuerpos Antineoplásicos/uso terapéutico , Células de la Médula Ósea/inmunología , Antígeno CD52 , Estudios de Cohortes , Citometría de Flujo , Humanos , Inmunofenotipificación , Leucemia de Células Pilosas/tratamiento farmacológico , Leucocitos/inmunología , Masculino , Persona de Mediana EdadRESUMEN
An immunocompetent 29-year-old male presented with an embolic stroke from an unusual primary cardiac lymphoma. The cardiac lesion consisted of a polypoid, left atrial, mural fibrin thrombus with anaplastic tumor cells lining the surface of the clot. Histologic, immunophenotypic, and molecular characterizations were consistent with a diagnosis of CD30+ large B-cell lymphoma with anaplastic cytology. While tumor emboli from invasive primary cardiac lymphomas have been reported, this noninvasive fibrin thrombus-associated lymphoma appears to be unique and previously unreported.