RESUMEN
The psychosocial consequences of the COVID-19 pandemic caused multifaceted challenges in clinical and therapeutic practices. This was the case at the Therapeutic Apheresis Unit of the Padua University Hospital too. Several published reports describe the increase in alcohol and food addiction diseases. In this context, during the last months, the Padua Therapeutic Apheresis Unit treated many more patients with acute pancreatitis due to severe hypertriglyceridemia with therapeutic plasma exchange than in the previous ten years. Furthermore, retrospective cohort studies have been recently published describing the onset of acute pancreatitis during the COVID-19 infection even if, to date, there is still insufficient evidence to estabilish a direct causality. Anyway, the COVID-19 pandemic translated into changes of the overall disease prevalence scenario and therefore the Padua Therapeutic Apheresis Unit will need to reorganise its Therapeutic Apheresis activity.
Asunto(s)
Hipertrigliceridemia/complicaciones , Pancreatitis/etiología , Pancreatitis/fisiopatología , Pancreatitis/terapia , Intercambio Plasmático/métodos , Adulto , COVID-19 , Femenino , Humanos , Hipertrigliceridemia/fisiopatología , Masculino , Persona de Mediana Edad , SARS-CoV-2RESUMEN
In the field of advanced melanoma, there is an urgent need to investigate novel approaches targeting specific components of the cancer-immunity cycle beyond immune checkpoint inhibitors. The authors reviewed the basic understanding of the role of neutrophils in cancer biology, and the latest clinical evidence supporting the correlation between cancer-associated neutrophils and the prognosis and response to the immunotherapy of advanced melanoma. Finally, they propose that granulocyte and monocyte apheresis, an emerging non-pharmacological treatment in current dermatology, could become an investigative treatment targeting melanoma-associated neutrophils which could be potentially used in combination with the usual immune checkpoint inhibitors.
Asunto(s)
Eliminación de Componentes Sanguíneos , Melanoma , Humanos , Inhibidores de Puntos de Control Inmunológico , Melanoma/tratamiento farmacológico , Inmunoterapia , GranulocitosRESUMEN
The novel coronavirus disease 2019 has grown to be a global public health emergency. The rapid spread of the infection has raised many questions in the oncohematological scientific community regarding the appropriateness of high-dose chemotherapy with autologous stem cell transplantation (ASCT). We here report two cases of patients who received ASCT at our Institute during the epidemic in Italy, affected with Hodgkin lymphoma and germ cell tumor, respectively. The two patients underwent a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on hospital admittance and during the period of bone marrow aplasia. They were attended to exclusively by dedicated health care staff who followed specifically implemented protocols for bedside nursing and care. They completed the procedure without unexpected side effect. Our experience demonstrates how ASCT can be performed safely if procedures are reorganized ad hoc to reduce the risk of SARS-CoV-2 infection.
Asunto(s)
COVID-19/prevención & control , Tumor del Seno Endodérmico/terapia , Trasplante de Células Madre Hematopoyéticas/normas , Enfermedad de Hodgkin/terapia , Control de Infecciones/normas , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/transmisión , Prueba de COVID-19/normas , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/inmunología , Humanos , Masculino , Pandemias/prevención & control , Ropa de Protección/normas , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/normas , Trasplante Autólogo/normas , Resultado del TratamientoRESUMEN
In Italy therapeutic apheresis procedures were carried out for the first time in the '70s. in the '80s the Italian Society of Hemapheresis was founded, formerly named SIDE, now SIdEM (Italian Society of Hemapheresis and Cellular Manipulation). From the beginning, the collection and the analysis of activity data have been seen as a way to improve the knowledge on mechanisms of action, to identify the correct rationale in order to intervene in the most appropriate clinical indications. Over the years the data collection has been refreshed and today we can rely on information representing the evolution of TA in Italy, from an organizational/technological viewpoint and according to clinical indications. Over the years the aspects that have mainly changed are the technologies, the organizational and managerial aspects and, above all, the clinical indications. The primary indication for therapeutic apheresis is still today the thrombotic thrombocytopenic purpura, but corrently, whenever a disease recognizes an autoimmune pathogenesis, the use of apheresis may be a valid therapeutic tool in the event of failure or partial efficacy of conventional drug therapy. The continuous monitoring of apheresis activity through Registries is a useful tool to follow the evolution of the apheresis practice.
Asunto(s)
Eliminación de Componentes Sanguíneos , Sistema de Registros , Eliminación de Componentes Sanguíneos/historia , Eliminación de Componentes Sanguíneos/métodos , Historia del Siglo XX , Historia del Siglo XXI , Humanos , ItaliaRESUMEN
INTRODUCTION: Therapeutic apheresis (TA) represents a treatment option for pre-existing conditions or diseases occurring during gestation. Although pregnancy is not a contraindication per se, due to the lack of evidence-based guidelines and presumed risk of maternal/fetal adverse events there is a general resistance to its application. MATERIAL AND METHODS: Between January 2005 and August 2017, at the Apheresis Unit of the University Hospital of Padua 936 TA procedures were performed during 57 pregnancies in 48 patients: 813 Plasma Exchange sessions, 119 Immunoadsorptions, 4 Red Blood Cell exchanges. The treated disease were as follows: antiphospholipid syndrome (18 patients), autoimmune congenital heart block (18), myasthenia gravis (3), Rh alloimmunization (2), systemic sclerosis (1), suspected autoimmune encephalitis (1), severe hypertriglyceridaemia (1), post partum hemolytic-uremic syndrome (1), sickle cell disease (1), lupus nephritis (1) and thrombotic thrombocytopenic purpura (1). RESULTS: In the time period considered the apheresis sessions applied to pregnant women were 7.1% of the total (nâ¯=â¯13.251). The median age at the first treatment was 33 years. The median week of gestation (WG) at the beginning of treatments was 21. Twenty (2.1%) sessions were complicated by adverse events, none requiring or prolonging hospitalization. There were 50 live births, 5 spontaneous abortions and 2 voluntary terminations of pregnancy. Median WG at delivery was 35 and caesarean section was performed in 46 cases. CONCLUSIONS: Our data showed that TA in pregnancy is well tolerated. Close collaboration between clinician, obstetrician and TA specialist is crucial to ensure a good outcome of high-risk pregnancies.
Asunto(s)
Intercambio Plasmático , Complicaciones del Embarazo/terapia , Resultado del Embarazo , Adulto , Femenino , Humanos , Embarazo , Complicaciones del Embarazo/sangre , Estudios RetrospectivosRESUMEN
Post-thrombotic syndrome (PTS) has been associated to DVT recurrence, increased FVIII, inflammatory biomarker plasma levels, and persistence of vein obstruction. These same features have also been widely reported in non-O blood type subjects. Our aim was to investigate the correlation between the incidence of PTS and ABO blood types. Consecutive patients referred to the Department of Medicine of University of Padua between January 2004 and January 2012 following the diagnosis of a first episode of proximal DVT were enrolled. The presence of PTS was assessed via the Villalta scale at predefined time points (3, 6, 12, 18, 24, 36 months). Hazard ratio (HR) for PTS development was calculated in non-O (exposed) vs O blood (unexposed) type patients. Out of 671 eligible patients, 606 were enrolled. Overall, 192 (31.7%) patients developed PTS: 142 (34.5%) non-O and 50 (25.6%) O blood type patients. Individuals with non-O blood group were associated with a significantly higher risk to develop PTS (HR 1.53, 95% CI, 1.05-2.24; p = 0.028) than O group. Non-O blood type might be a risk factor for the development of PTS.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/inmunología , Síndrome Postrombótico/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hospitales Universitarios , Humanos , Incidencia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Síndrome Postrombótico/sangre , Síndrome Postrombótico/epidemiología , Síndrome Postrombótico/inmunología , Prevalencia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Prevención Secundaria , Adulto JovenRESUMEN
Organ transplantation represents the preferred treatment option for many patients in terminal organ failure. The half-life of transplanted organs, however, is still far from being satisfactory with the vast majority of the organs failing within the first two decades following transplantation. At this stage, it has become apparent that rejection (prevalently mediated by humoral events) remains the primary cause of graft loss after the first year. In this light, studies are underway to better comprehend the immune events underlying graft rejection and novel immunosuppressive strategies are being explored. In this context, therapeutic apheresis techniques, that include therapeutic plasma exchange (TPE), immunoadsorption (IA) and extracorporeal photochemotherapy (ECP), represent an important adjunct in the current immunosuppressive armamentarium. This article briefly reviews our current understanding of the immune process underlying rejection of a solid organ transplant and describes the principal areas of application of therapeutic apheresis techniques in transplantation.
Asunto(s)
Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Hemofiltración , Trasplante de Órganos , Fotoféresis , Intercambio Plasmático , Rechazo de Injerto/patología , HumanosRESUMEN
INTRODUCTION: Despite prophylaxis, a small proportion of RhD-negative women may develop anti-D antibodies after a sensitizing event occurring during pregnancy or delivery of a D-positive baby. Intrauterine transfusion (IUT) is the treatment of choice in case of fetal anemia, but it cannot be performed early during pregnancy. Combined treatment with therapeutic plasma-exchange (TPE) and intravenous immunoglobulin (IVIG) can avoid or delay IUT. Immunoadsorption (IA) could represent a more effective treatment in selected cases. CASE REPORT: We report a D-negative female with a history of induced abortion and hydrops fetalis, referred at 8 weeks of gestation with a high anti-D titer. Despite implementing a TPE-IVIG protocol, the patient experienced a spontaneous abortion. At the beginning of her fourth pregnancy, only after a partially effective intensive TPE course, cycles of IA-IVIG were performed. Despite a suboptimal response on the anti-D titer, Doppler ultrasonographic measurements of the fetal middle cerebral artery peak systolic velocity first showed evidence of anemia at 30 weeks of gestation and a IUT was required. After the IUT, anemia persisted with a subsequent dramatic rise in titer, requiring an emergent cesarean section. The infant subsequently underwent successful treatment with IVIG, phototherapy and exchange transfusion and was discharged 7 weeks later without neurological deficits. DISCUSSION: The treatment of high titer anti-D antibodies during pregnancy may require a multidisciplinary approach with utilization of different apheresis strategies in order to have a successful pregnancy outcome.
Asunto(s)
Inmunoglobulinas Intravenosas/uso terapéutico , Plasmaféresis/métodos , Isoinmunización Rh/tratamiento farmacológico , Adulto , Femenino , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Embarazo , Isoinmunización Rh/mortalidad , Isoinmunización Rh/patologíaRESUMEN
Pyoderma gangrenosum is a neutrophilic dermatosis clinically characterised by the presence of painful skin ulcerations with erythematous and undetermined borders and histologically by the presence of neutrophilic infiltrates in the dermis. Granulocyte and monocyte adsorption apheresis, also called granulocytapheresis, is a therapeutic strategy for extracorporeal immunomodulation that selectively removes activated granulocytes and monocytes/macrophages from the peripheral blood. Here, we report a case of a 73-year-old patient affected by a severe form of pyoderma gangrenosum presenting with multiple painful ulcers and pustules on his trunk and extremities. The disease was resistant to high doses of methylprednisolone and methotrexate and successfully treated by granulocyte and monocyte adsorption apheresis. To the best of our knowledge, this is the first report on the efficacy of granulocyte and monocyte adsorption apheresis in pyoderma gangrenosum in Europe.
Asunto(s)
Adsorción/fisiología , Eliminación de Componentes Sanguíneos/métodos , Granulocitos/fisiología , Monocitos/fisiología , Piodermia Gangrenosa/terapia , Anciano , Europa (Continente) , Humanos , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: AL amyloidosis is a rare plasma cell dyscrasia with multiorgan involvement. Good risk patients are candidate to high dose chemotherapy and autologous stem cell transplantation. However both transplantation and stem cell collection entail significant risk in such patients. Plerixafor is a novel mobilizing agent approved for use in "poor mobilizer" patients with lymphoma and multiple myeloma; experience in systemic amyloidosis patients is limited. CASE REPORT: We describe a case of spontaneous splenic rupture following administration of G-CSF and plerixafor in a patient with AL amyloidosis who previously underwent heart transplantation due to amyloid heart involvement. RESULTS AND CONCLUSION: This is the first report of spontaneous splenic rupture following stem cell mobilization with G-CSF and plerixafor in AL amyloidosis. The role of plerixafor has to be established. AL amyloidosis patients undergoing stem cell mobilization need careful monitoring of signs and symptoms of spontaneous splenic rupture.
Asunto(s)
Amiloidosis/terapia , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Movilización de Célula Madre Hematopoyética/efectos adversos , Compuestos Heterocíclicos/efectos adversos , Rotura del Bazo/etiología , Adulto , Amiloidosis/patología , Bencilaminas , Ciclamas , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Compuestos Heterocíclicos/administración & dosificación , Humanos , Rotura Espontánea , Rotura del Bazo/patologíaRESUMEN
It is widely known that pregnancy does not represent a contraindication to therapeutic apheresis (TA) techniques. In fact, since the first experiences of TA in pregnancy for the prevention of hemolytic disease of the newborn, several diseases are at present treated with TA, mainly within 6 clinical categories: (a) TA is a priority and has no alternative equally effective treatment (e.g., thrombotic thrombocytopenic purpura); (b) TA is a priority but there are alternative therapies not contraindicated in pregnancy (e.g., myasthenia gravis); (c) TA is an effective tool of saving/avoiding drugs contraindicated in pregnancy (e.g., systemic lupus erythematosus); (d) TA is a treatment of specific conditions/complications of pregnancy with maternal and/or fetal risk (e.g., antiphospholipid syndrome); (e) TA is a treatment of specific conditions of pregnancy with exclusive fetal risk (e.g., hemolytic disease of the newborn); (f) TA is a treatment of disease which is strongly indicated and can exceptionally occur during pregnancy (e.g., Goodpasture's syndrome). When dealing with TA pregnant patients, some technical aspects due to the physiological changes of gestation have to be carefully considered, in particular the increase of the circulating blood volume. Moreover a multidisciplinary medical team, including an obstetrician, a clinical consultant, specialist in TA and in transfusion medicine, and a neonatologist stand as a basic requirement for the proper management of some clinical conditions that may be characterized by high maternal and fetal risk.
Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Eritroblastosis Fetal/prevención & control , Complicaciones Hematológicas del Embarazo/terapia , Femenino , Humanos , Guías de Práctica Clínica como Asunto , EmbarazoRESUMEN
Primary hyperthyroidism is an endocrine disorder characterized by excessive thyroid hormone synthesis and secretion by the thyroid gland. Clinical manifestations of hyperthyroidism can vary from subclinical to overt forms. In rare cases, hyperthyroidism may represent a clinical emergency, requiring admission to an intensive care unit due to an acute and severe exacerbation of thyrotoxicosis, known as a thyroid storm. First-line treatment of hyperthyroidism is almost always based on medical therapy (with thioamides, beta-adrenergic blocking agents, glucocorticoids), radioactive iodine or total thyroidectomy, tailored to the patient's diagnosis. In cases of failure/intolerance/adverse events or contraindication to these therapies, as well as in life-threatening situations, including a thyroid storm, it is necessary to consider an alternative treatment with extracorporeal systems, such as therapeutic plasma exchange (TPE). This approach can promptly resolve severe conditions by removing circulating thyroid hormones. Here we described two different applications of TPE in clinical practice: the first case is an example of thyrotoxicosis due to amiodarone treatment, while the second one is an example of a severe adverse event to antithyroid drugs (agranulocytosis induced by methimazole).
RESUMEN
Despite the relatively high long-term disease-free survival (DFS) rate for patients with Hodgkin lymphoma (HL) with modern combination chemotherapy or combined modality regimens, â¼20% of patients die from progressive or relapsed disease. The standard treatment for relapsed and primary refractory HL is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), which has shown a 5-year progression-free survival rate of â¼50%-60%. Recent developments in a number of diagnostic and therapeutic modalities have begun to improve these results. Functional imaging, refinement of clinical prognostic factors, and development of novel biomarkers have improved the predictive algorithms, allowing better patient selection and timing for ASCT. In addition, these algorithms have begun to identify a group of patients who are candidates for more aggressive treatment beyond standard ASCT. Novel salvage regimens may potentially improve the rate of complete remission prior to ASCT, and the use of maintenance therapy after ASCT has become a subject of current investigation. We present a summary of developments in each of these areas.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/cirugía , Terapia Combinada , Supervivencia sin Enfermedad , Enfermedad de Hodgkin/patología , Humanos , Pronóstico , Recurrencia , Terapia Recuperativa , Acondicionamiento Pretrasplante , Resultado del TratamientoRESUMEN
Chemotherapy-induced peripheral neurotoxicity is a major problem because it represents the dose-limiting side effect of a significant number of antineoplastic drugs, such as vinca alkaloids. Hereditary neuropathies usually predispose to severe vincristine neurotoxicity. Here, we report the case of a 56-year-old man with Machado-Joseph disease, also known as spinocerebellar ataxia type 3, treated with a vinca alkaloid without exacerbation of neurological symptoms.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Enfermedad de Machado-Joseph/tratamiento farmacológico , Vincristina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Tomografía de Emisión de Positrones , Pronóstico , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Glycogen Synthase Kinase-3 (GSK-3) α and ß are two serine-threonine kinases controlling insulin, Wnt/ß-catenin, NF-κB signaling and other cancer-associated transduction pathways. Recent evidence suggests that GSK-3 could function as growth-promoting kinases, especially in malignant cells. In this study, we have investigated GSK-3α and GSK-3ß function in multiple myeloma (MM). METHODS: GSK-3 α and ß expression and cellular localization were investigated by Western blot (WB) and immunofluorescence analysis in a panel of MM cell lines and in freshly isolated plasma cells from patients. MM cell growth, viability and sensitivity to bortezomib was assessed upon treatment with GSK-3 specific inhibitors or transfection with siRNAs against GSK-3 α and ß isoforms. Survival signaling pathways were studied with WB analysis. RESULTS: GSK-3α and GSK-3ß were differently expressed and phosphorylated in MM cells. Inhibition of GSK-3 with the ATP-competitive, small chemical compounds SB216763 and SB415286 caused MM cell growth arrest and apoptosis through the activation of the intrinsic pathway. Importantly, the two inhibitors augmented the bortezomib-induced MM cell cytotoxicity. RNA interference experiments showed that the two GSK-3 isoforms have distinct roles: GSK-3ß knock down decreased MM cell viability, while GSK-3α knock down was associated with a higher rate of bortezomib-induced cytotoxicity. GSK-3 inhibition caused accumulation of ß-catenin and nuclear phospho-ERK1, 2. Moreover, GSK-3 inhibition and GSK-3α knockdown enhanced bortezomib-induced AKT and MCL-1 protein degradation. Interestingly, bortezomib caused a reduction of GSK-3 serine phosphorylation and its nuclear accumulation with a mechanism that resulted partly dependent on GSK-3 itself. CONCLUSIONS: These data suggest that in MM cells GSK-3α and ß i) play distinct roles in cell survival and ii) modulate the sensitivity to proteasome inhibitors.
Asunto(s)
Ácidos Borónicos/farmacología , Regulación de la Expresión Génica , Glucógeno Sintasa Quinasa 3/metabolismo , Mieloma Múltiple/metabolismo , Pirazinas/farmacología , Transporte Activo de Núcleo Celular , Antineoplásicos/farmacología , Apoptosis , Bortezomib , Muerte Celular , Núcleo Celular/metabolismo , Proliferación Celular , Silenciador del Gen , Glucógeno Sintasa Quinasa 3 beta , Humanos , Potenciales de la Membrana , Fosforilación , Interferencia de ARN , Transducción de SeñalRESUMEN
We present the case of a woman with a severe clinical history of antiphospholipid syndrome and persistent positivity for lupus anticoagulant, IgG anticardiolipin and IgG anti-ß2Glycoprotein I antibodies. An acute clinical onset characterized by severe abdominal pain immediately followed by circulatory shock and histological colonic small vessel thrombosis pattern pointed to a diagnosis of ischemic colitis. The subsequent rapid onset of pulmonary alveolitis and heart failure associated to subendocardial hypoperfusion led to a diagnosis of definite catastrophic antiphospholipid syndrome (CAPS). Conventional triple therapy together with a broad-spectrum preventive antibiotic therapy were quickly initiated, and the outcome was favorable. We evaluated the patients with ischemic colitis in CAPS described in the literature between 1992 and May 2019 and our CAPS case. In accordance with the "two-hit" hypothesis and on the basis of the patients' data, we would like to speculate that the colonic wall necrosis related to ischemic colitis damaged the intestinal barrier causing loss of resistance to bacteria and leading to endotoxemia and bacteremia with bacteria translocation through the circulatory stream to the lungs and heart. The bacteria acted as the priming factor which favored the binding of ß2Glycoprotein I to the endothelium vessels in the colon, lungs, and heart following activation of anti-ß2Glycoprotein I antibodies which attached to the domain I of ß2Glycoprotein I. This was followed by complement activation which triggered the thrombotic and cytokine storm. If further clinical studies confirm this hypothesis, the treatment of CAPS could be more targeted and effective.