RESUMEN
The present study presents an alternative analytical workflow that combines mid-infrared (MIR) microscopic imaging and deep learning to diagnose human lymphoma and differentiate between small and large cell lymphoma. We could show that using a deep learning approach to analyze MIR hyperspectral data obtained from benign and malignant lymph node pathology results in high accuracy for correct classification, learning the distinct region of 3900 to 850 cm-1 . The accuracy is above 95% for every pair of malignant lymphoid tissue and still above 90% for the distinction between benign and malignant lymphoid tissue for binary classification. These results demonstrate that a preliminary diagnosis and subtyping of human lymphoma could be streamlined by applying a deep learning approach to analyze MIR spectroscopic data.
Asunto(s)
Aprendizaje Profundo , Linfoma , Humanos , Linfoma/diagnóstico por imagen , Linfoma/patología , Diagnóstico Diferencial , Ganglios Linfáticos , Diagnóstico por ImagenRESUMEN
INTRODUCTION: We analyzed the expression of PD-L1 in human lymphomas using hyperspectral imaging (HSI) compared to visual assessment (VA) and conventional digital image analysis (DIA) to strengthen further the value of HSI as a tool for the evaluation of brightfield-based immunohistochemistry (IHC). In addition, fluorescent multiplex immunohistochemistry (mIHC) was used as a second detection method to analyze the impact of a different detection method. MATERIAL AND METHODS: 18 cases (6 follicular lymphomas and 12 diffuse large B-cell lymphomas) were stained for PD-L1 by IHC and for PD-L1, CD3, and CD8 by fluorescent mIHC. The percentage of positively stained cells was evaluated with VA, HSI, and DIA for IHC and VA and DIA for mIHC. Results were compared between the different methods of detection and analysis. RESULTS: An overall high concordance was found between VA, HSI, and DIA in IHC (Cohens Kappa = 0.810VA/HSI, 0.710 VA/DIA, and 0.516 HSI/DIA) and for VAmIHCversus DIAmIHC (Cohens Kappa = 0.894). Comparing IHC and mIHC general agreement differed depending on the methods compared but reached at most a moderate agreement (Cohens Kappa between 0.250 and 0.483). This is reflected by the significantly higher percentage of PD-L1+ cells found with mIHC (pFriedman = 0.014). CONCLUSION: Our study shows a good concordance for the different analysis methods. Compared to VA and DIA, HSI proved to be a reliable tool for assessing IHC. Understanding the regulation of PD-L1 expression will further enlighten the role of PD-L1 as a biomarker. Therefore it is necessary to develop an instrument, such as HSI, which can offer a reliable and objective evaluation of PD-L1 expression.
Asunto(s)
Neoplasias Pulmonares , Linfoma , Humanos , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Inmunohistoquímica , Imágenes Hiperespectrales , Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/diagnósticoRESUMEN
BACKGROUND: In patients with multiple myeloma (MM) free light chain-induced cast nephropathy is a serious complication associated with poor survival. High-cut-off (HCO) hemodialysis can reduce the amount of serum free light chains (sFLC), but data on its impact on clinical outcome is limited and contradictory. To gain further insights we collected real world data from two major myeloma and nephrology centers in Austria and the Czech Republic. METHODS: Sixty-one patients with MM and acute kidney injury, who were treated between 2011 and 2019 with HCO hemodialysis and bortezomib-based MM therapy, were analyzed. RESULTS: The median number of HCO hemodialysis sessions was 11 (range 1-42). Median glomerular filtration rate at diagnosis was 7 ± 4.2 ml/min/1.73m2. sFLC after the first HCO hemodialysis decreased by 66.5% and by 89.2% at day 18. At 3 and 6 months, 26 (42.6%) and 30 (49.2%) of patients became dialysis-independent. CONCLUSION: The widely used strategy combining HCO hemodialysis and bortezomib-based antimyeloma treatment is dissatisfactory for half of the patients undergoing it and clearly in need of improvement.
Asunto(s)
Lesión Renal Aguda , Mieloma Múltiple , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/terapia , Bortezomib/efectos adversos , Humanos , Cadenas Ligeras de Inmunoglobulina , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Diálisis Renal/efectos adversosRESUMEN
In a phase 3 trial of denosumab vs zoledronic acid in patients (n=1776) with bone metastases and solid tumors or multiple myeloma, denosumab was superior to zoledronic acid for the primary end point of prevention of skeletal-related events. There was no difference in overall survival between the two groups; however, an ad hoc overall survival analysis in the multiple myeloma subset of patients (n=180) favored zoledronic acid (hazard ratio (HR) 2.26; 95% confidence interval (CI) 1.13-4.50; P=0.014). In the present analysis, we found imbalances between the groups with respect to baseline risk characteristics. HRs with two-sided 95% CIs were estimated using the Cox model. After adjustment in a covariate analysis, the CI crossed unity (HR 1.86; 95% CI 0.90-3.84; P=0.0954). Furthermore, we found a higher rate of early withdrawals for the reasons of lost to follow-up and withdrawal of consent in the zoledronic acid group; after accounting for these, the HR was 1.31 (95% CI 0.80-2.15; P=0.278). In conclusion, the survival results in multiple myeloma patients in this trial were confounded and will eventually be resolved by an ongoing phase 3 trial.
Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Denosumab/uso terapéutico , Difosfonatos/uso terapéutico , Imidazoles/uso terapéutico , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Denosumab/administración & dosificación , Denosumab/efectos adversos , Difosfonatos/administración & dosificación , Difosfonatos/efectos adversos , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Imidazoles/administración & dosificación , Imidazoles/efectos adversos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias/patología , Trasplante Autólogo , Resultado del Tratamiento , Ácido ZoledrónicoRESUMEN
PURPOSE: The purpose of this study was to provide a clinician-friendly overview of decision-analytic models evaluating different treatment strategies for multiple myeloma (MM). METHODS: We performed a systematic literature search to identify studies evaluating MM treatment strategies using mathematical decision-analytic models. We included studies that were published as full-text articles in English, and assessed relevant clinical endpoints, and summarized methodological characteristics (e.g., modeling approaches, simulation techniques, health outcomes, perspectives). RESULTS: Eleven decision-analytic modeling studies met our inclusion criteria. Five different modeling approaches were adopted: decision-tree modeling, Markov state-transition modeling, discrete event simulation, partitioned-survival analysis and area-under-the-curve modeling. Health outcomes included survival, number-needed-to-treat, life expectancy, and quality-adjusted life years. Evaluated treatment strategies included novel agent-based combination therapies, stem cell transplantation and supportive measures. CONCLUSION: Overall, our review provides a comprehensive summary of modeling studies assessing treatment of MM and highlights decision-analytic modeling as an important tool for health policy decision making.
Asunto(s)
Toma de Decisiones , Técnicas de Apoyo para la Decisión , Simulación por Computador , Análisis Costo-Beneficio , Manejo de la Enfermedad , Humanos , Modelos Estadísticos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Análisis de SupervivenciaRESUMEN
Bortezomib-dexamethasone (Btz/Dex) is an active regimen in patients with multiple myeloma and has been used in few patients with amyloidosis. Here, we report a retrospective evaluation of the efficacy and toxicity of Btz/Dex in 26 patients with AL amyloidosis (AL). Eighteen patients (69%) received Btz/Dex as first-line treatment. Organs most frequently involved were kidneys (100%) and heart (35%); five patients (19%) had less than two organs involved. The overall response rate was 54% (14 of 26 patients), with eight patients (31%) achieving a hematologic complete remission (CR). All patients who reached a CR received Btz/Dex as first-line therapy. Median time to response was 7.5 weeks. Improvement in organ function was noticed in three patients (12%). Median progression-free survival (PFS) and overall survival (OS) was 5.0 and 18.7 months, respectively; in CR patients, however, median PFS and OS have not yet been reached. Toxicities were manageable, with hematological side effects being most common. No grade 3/4 neuropathy was observed. Our results confirm the activity of bortezomib/dexamethasone in patients with AL amyloidosis and suggest that patients achieving a CR have a marked benefit for survival.
Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ácidos Borónicos/uso terapéutico , Dexametasona/uso terapéutico , Pirazinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Amiloidosis/tratamiento farmacológico , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ácidos Borónicos/efectos adversos , Bortezomib , Dexametasona/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Masculino , Persona de Mediana Edad , Pirazinas/efectos adversos , Inducción de Remisión , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Trasplante de Médula Ósea/inmunología , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas , Inmunoglobulina G/uso terapéutico , Inmunosupresores/uso terapéutico , Ácido Micofenólico/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/fisiopatología , Daclizumab , Quimioterapia Combinada , Humanos , Inmunoglobulina G/efectos adversos , Inmunosupresores/efectos adversos , Ácido Micofenólico/análogos & derivados , Activación ViralRESUMEN
Hematopoietic stem cell transplantation (HSCT) is a treatment option for autoimmune diseases but can also cause clinical features similar to those of autoimmune diseases. In some of these cases the autoimmune-like condition is associated with autoimmune cytopenia, a complication that can be unresponsive to established treatment strategies and which may be fatal. The majority of cases reported on immune hemolytic anemia have been of alloimmune origin due to ABO red blood cell antigen incompatibilities between donor and recipient. We now report a patient with a lupus-like syndrome, presenting with severe thrombocytopenia and hemolytic anemia 9 months after HLA-mismatch, ABO compatible-related PBSCT who experienced no response to high-dose steroids, but who had a sustained response to repeated IvIG therapy.
Asunto(s)
Anemia Hemolítica/tratamiento farmacológico , Enfermedad Injerto contra Huésped/diagnóstico , Trombocitopenia/tratamiento farmacológico , Trasplante Homólogo/efectos adversos , Adulto , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/etiología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/etiología , Diagnóstico Diferencial , Supervivencia sin Enfermedad , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Prueba de Histocompatibilidad/efectos adversos , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Lupus Vulgar/diagnóstico , Masculino , Recuento de Plaquetas , Trombocitopenia/diagnóstico , Trombocitopenia/etiologíaRESUMEN
Competitive inhibition of interleukin 2-dependent lymphocytes by daclizumab demonstrates some beneficial effects in the treatment of graft-versus-host disease (GVHD). Sixteen patients with steroid refractory GVHD received daclizumab (1 mg/kg BW) on d 1, 2 (-5), 7, 14 and 21. Twelve patients suffered from grade III-IV acute GVHD and four patients from extensive chronic GVHD. Responses were observed in nine patients (six acute, three chronic GVHD). Fourteen out of 16 patients acquired infections during daclizumab treatment and three deaths were infection related. Daclizumab demonstrates limited activity and is associated with an increased incidence of infectious complications.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Inmunoglobulina G/uso terapéutico , Inmunosupresores/uso terapéutico , Receptores de Interleucina-2/inmunología , Enfermedad Aguda , Adulto , Anticuerpos Monoclonales Humanizados , Enfermedad Crónica , Daclizumab , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Hepatopatías/tratamiento farmacológico , Hepatopatías/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/inmunología , Insuficiencia del TratamientoRESUMEN
GVHD continues to be a major complication after allogeneic hematopoietic stem cell transplantation even when the recipient is given immunosuppression for the prophylaxis of this severe disease. There have been many advances in the prevention and treatment of GVHD, using compounds such as cyclosporine, FK506, mycophenolate mofetil or monoclonal IL-2 receptor antagonist. New strategies seem to include sequential therapy involving the blocking of both endogenous cytokines and alloreactive donor cells. However, further clinical and laboratory studies are needed in order to improve the therapy of established GVHD.
Asunto(s)
Enfermedad Injerto contra Huésped/terapia , Enfermedad Aguda , Adulto , Anticuerpos Monoclonales/uso terapéutico , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inmunosupresores/uso terapéutico , Leucemia/terapia , Masculino , Persona de Mediana Edad , Trasplante HomólogoAsunto(s)
Antibióticos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/efectos adversos , Enfermedades Pulmonares/inducido químicamente , Antibióticos Antineoplásicos/administración & dosificación , Bleomicina/administración & dosificación , Cisplatino/administración & dosificación , Etopósido/administración & dosificación , Germinoma/tratamiento farmacológico , Humanos , Ifosfamida/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
We measured the levels of the cytokines IL-1-alpha, IL-1-beta, IL-2, IL-6, TNF-alpha, and IFN-gamma in culture supernatants of stimulated whole blood cells derived from 23 tumor patients undergoing a 4-week oral treatment with a spagyric extract from Echinacea angustifolia, Eupatorium perfoliatum, and Thuja occidentalis (Echinacea complex). All patients had had curative surgery for a localized solid malignant tumor. Blood was taken before treatment and after 2 and 4 weeks of therapy. Twelve untreated tumor patients at the same clinical stage, also after curative surgery, served as a control group. In the blood cell cultures of all patients, a rather wide range of cytokine levels was found. After therapy with Echinacea complex, no significant alteration in the production of the cytokines could be seen in comparison to the controls, and also the leukocyte populations remained constant. We conclude that at this application and dosage, the therapy with Echinacea complex has no detectable effect on tumor patients' lymphocytes activity as measured by their cytokine production.
Asunto(s)
Citocinas/metabolismo , Leucocitos/efectos de los fármacos , Extractos Vegetales/farmacología , Plantas Medicinales , Administración Oral , Adulto , Anciano , Antígenos CD/inmunología , Antineoplásicos/farmacología , Femenino , Humanos , Interferón gamma/metabolismo , Interleucinas/metabolismo , Recuento de Leucocitos , Leucocitos/química , Masculino , Persona de Mediana Edad , Mitógenos/farmacología , Neoplasias/terapia , Extractos Vegetales/uso terapéutico , Linfocitos T/clasificación , Linfocitos T/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
To investigate the interaction of herpes simplex virus type 1 (HSV-1) with the cell surface, we studied the formation of complexes by HSV-1 virion proteins with biotinylated cell membrane components. HSV-1 virion proteins reactive with surface components of HEp-2 and other cells were identified as gC, gB, and gD. Results from competition experiments suggested that binding of gC, gB, and gD occurred in a noncooperative way. The observed complex formation could be specifically blocked by monospecific rabbit antisera against gB and gD. The interaction of gD with the cell surface was also inhibited by monoclonal antibody IV3.4., whereas other gD-specific monoclonal antibodies, despite their high neutralizing activity, were not able to inhibit this interaction. Taken together, these data provide direct evidence that at least three of the seven known HSV-1 glycoproteins are able to form complexes with cellular surface structures.