RESUMEN
BACKGROUND: A prior practice survey revealed variations in the management of patients with sickle cell disease (SCD) and stressed the need for comprehensive guidelines. Here we discuss: 1) common indications for red blood cell exchange (RCE), 2) options for access, 3) how to prepare the red blood cells (RBCs) to be used for RCE, 4) target hemoglobin (Hb) and/or hematocrit (Hct) and HbS level, 5) RBC depletion/RCE, and 6) some complications that may ensue. STUDY DESIGN AND METHODS: Fifteen physicians actively practicing apheresis from 14 institutions representing different areas within the United States discussed how they manage RCE for patients with SCD. RESULTS: Simple transfusion is recommended to treat symptomatic anemia with Hb level of less than 9 g/dL. RCE is indicated to prevent or treat complications arising from the presence of HbS. The most important goals are reduction of HbS while also preventing hyperviscosity. The usual goals are a target HbS level of not more than 30% and Hct level of less than 30%. CONCLUSION: Although a consensus as to protocol details may not be possible, there are areas of agreement in the management of these patients, for example, that it is optimal to avoid hyperviscosity and iron overload, that a target Hb S level in the range of 30% is generally desirable, and that RCE as an acute treatment for pain crisis in the absence of other acute or chronic conditions is ordinarily discouraged.
Asunto(s)
Anemia de Células Falciformes/terapia , Transfusión de Eritrocitos/métodos , Viscosidad Sanguínea , Manejo de la Enfermedad , Hemoglobina Falciforme/análisis , Humanos , Sobrecarga de Hierro/prevención & control , Estados UnidosRESUMEN
We reported that PIM1 kinase is expressed in the lymphocytes of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Quercetin, a naturally occurring flavonoid, is a dietary supplement and inhibits many kinases, including PIM1, in vitro. Under an Institutional Review Board-approved protocol, we performed an open-label, single-arm pilot study to evaluate the antitumor activity of quercetin in patients with CLL/SLL. Q-ForceTM chews were administered orally, 500 mg twice daily, for 3 months. Eligible patients had failed prior therapies, had had no other standard treatment, or refused other therapies. Response was assessed based on objective change in disease parameters. Patients were included if their lymphocyte counts were rising and ≥10,000/µL but not > 100,000/µL. Three patients received quercetin treatment. There was no toxicity. Two responded with stabilization of rising lymphocyte counts (p < 0.001 for each), which remained stable during their follow-up (5 and 11 months after cessation of treatment, respectively). The CLL cells in the nonresponder harbored a TP53 mutation. Although our data from this pilot translational study are based on a small sample, further studies of quercetin as a potential therapeutic agent in selected patients with CLL/SLL appear warranted.
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Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/metabolismo , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Quercetina/uso terapéutico , Anciano , Biomarcadores , Suplementos Dietéticos , Femenino , Humanos , Inmunohistoquímica , Leucemia Linfocítica Crónica de Células B/mortalidad , Persona de Mediana Edad , Selección de Paciente , Proyectos Piloto , Quercetina/administración & dosificación , Quercetina/efectos adversos , Resultado del TratamientoRESUMEN
We surveyed multiple apheresis centers represented by the authors for their clinical approach to the management of anticoagulation issues during therapeutic plasma exchange (TPE). We present the results of their practices and a review of the pertinent literature. As plasma is removed during TPE, replacement with all or partial non-plasma-containing fluids (eg, 5% albumin) may lead to significant changes in hemostasis. These changes are amplified in patients who are receiving anticoagulation. We discuss various anticoagulants as well as the monitoring and adjustment of anticoagulation before, during, and after TPE. No single guideline can be applied, but rather, patients must be monitored individually, taking into account their often complex clinical conditions and medication profiles.
Asunto(s)
Anticoagulantes/uso terapéutico , Intercambio Plasmático/métodos , Manejo de la Enfermedad , Monitoreo de Drogas/métodos , Humanos , Intercambio Plasmático/efectos adversosRESUMEN
The human BCL6 gene encodes a transcriptional repressor that is crucial for germinal center B cell development and T follicular helper cell differentiation. It is involved in the pathogenesis of certain human lymphomas. In an effort to identify targets of BCL6 repression, we used a previously described cell system in which BCL6 repressive effects are inhibited, followed by subtractive hybridization, and identified the integral membrane 2B gene (ITM2B, formerly BRI2) as a potential target. Here we show that BCL6 can bind to its preferential consensus binding site within the first intron of ITM2B and represses its transcription. Knockdown of endogenous BCL6 in a human B cell lymphoma line increases ITM2B expression. Further, there is an inverse relationship between the expression levels of BCL6 and ITM2B proteins in 16 human B- and T-cell lymphomas studied by immunohistochemistry. Both the BCL6 and ITM2B proteins are expressed ubiquitously. Similar to some other targets of BCL6, a short form of the ITM2B protein generated by alternative splicing induces apoptosis in hematopoietic cell lines. Molecular alterations in the ITM2B gene are associated with two neurodegenerative diseases, Familial British and Familial Danish dementia. ITM2B dysfunction also may be relevant for the development of Alzheimer's disease. Our data confirm ITM2B as a target of BCL6 repression in lymphoma. A further understanding of the genes that function as regulators of the ITM2B protein may provide insights for the development of new molecular tools not only for targeted lymphoma therapy but also for the treatment of these dementias.
Asunto(s)
Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Linfoma/genética , Glicoproteínas de Membrana/genética , Enfermedades Neurodegenerativas/genética , Proteínas Adaptadoras Transductoras de Señales , Animales , Northern Blotting , Western Blotting , Catarata/genética , Catarata/metabolismo , Catarata/patología , Línea Celular Tumoral , Ataxia Cerebelosa/genética , Ataxia Cerebelosa/metabolismo , Ataxia Cerebelosa/patología , Proteínas de Unión al ADN/metabolismo , Sordera/genética , Sordera/metabolismo , Sordera/patología , Demencia/genética , Demencia/metabolismo , Demencia/patología , Humanos , Inmunoprecipitación , Linfoma/metabolismo , Linfoma/patología , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Linfoma de Células B/patología , Glicoproteínas de Membrana/metabolismo , Ratones , Células 3T3 NIH , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Unión Proteica , Proteínas Proto-Oncogénicas c-bcl-6 , Interferencia de ARNRESUMEN
Diffuse large B-cell lymphomas in humans are associated with chromosomal rearrangements (â¼40%) and/or mutations disrupting autoregulation (â¼16%) involving the BCL6 gene. Studies of lymphoma development in humans and mouse models have indicated that lymphomagenesis evolves through the accumulation of multiple genetic alterations. Based on our prior studies, which indicated that carcinogen-induced DNA mutations enhance the incidence of lymphomas in our mouse model expressing a human BCL6 transgene, we hypothesized that mutated genes are likely to play an important cooperative role in BCL6-associated lymphoma development. We used retroviral insertional mutagenesis in an effort to identify which genes cooperate with BCL6 in lymphomagenesis in our BCL6 transgenic mice. We identified PIM1 as the most frequently recurring cooperating gene in our murine BCL6-associated lymphomas (T- and B-cell types), and we observed elevated levels of PIM1 mRNA and protein expression in these neoplasms. Further, immunohistochemical staining, which was performed in 20 randomly selected BCL6-positive human B- and T-cell lymphomas, revealed concurrent expression of BCL6 and PIM1 in these neoplasms. As PIM1 encodes a serine/threonine kinase, PIM1 kinase inhibition may be a promising therapy for BCL6/PIM1-positive human lymphomas.
Asunto(s)
Proteínas de Unión al ADN/genética , Linfoma/genética , Linfoma/patología , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Proteínas Proto-Oncogénicas c-pim-1/genética , Animales , Proteínas de Unión al ADN/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Ratones Transgénicos , Mutagénesis Insercional/genética , Proteínas Proto-Oncogénicas c-bcl-6 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Retroviridae/genética , Análisis de SupervivenciaRESUMEN
The BCL6 gene, which is expressed in certain B- and T-cell human lymphomas, is involved with chromosomal rearrangements and mutations in a number of these neoplasms. Lymphomagenesis is believed to evolve through a multi-step accumulation of genetic alterations in these tumors. We used retroviral insertional mutagenesis in transgenic mice expressing the human BCL6 transgene in order to identify genes that cooperate with BCL6 during lymphomatous transformation. We previously reported PIM1 as the most frequently recurring cooperating gene in this model. We now report three newly identified cooperating genes-GFI1B, EVI5, and MYB-that we identified in the lymphomas of retroviral-injected BCL6 transgenic mice (but not in retroviral-injected non-transgenic controls); mRNA and protein expression of GFI1B and EVI5 were decreased in the murine tumors, whereas MYB mRNA and protein expression were increased or decreased. These findings correlated with protein expression in human lymphomas, both B- and T-cell. Improved therapy of lymphomas may necessitate the development of combinations of drugs that target the alterations specific to each neoplasm.
Asunto(s)
Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Linfoma de Células B/genética , Linfoma de Células T/genética , Proteínas Oncogénicas v-myb/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Factores de Transcripción/genética , Animales , Proteínas de Ciclo Celular , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Proteínas de Unión al ADN/metabolismo , Femenino , Proteínas Activadoras de GTPasa , Vectores Genéticos , Humanos , Inmunohistoquímica , Linfoma de Células B/metabolismo , Linfoma de Células B/patología , Linfoma de Células T/metabolismo , Linfoma de Células T/patología , Masculino , Ratones , Ratones Transgénicos , Proteínas Oncogénicas v-myb/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-6 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Represoras/metabolismo , Retroviridae/genética , Transducción de Señal , Factores de Transcripción/metabolismoRESUMEN
Ammonia concentration increases in red cell units (RBCs) during storage. We measured absolute amounts of ammonia (AA) per unit serially in stored RBCs and before and after removal of the supernatant by volume reduction (VR) or washing. Ammonia increased 6.4-fold in untreated units over 31 days. VR decreased AA 3.7-fold, whereas washing decreased it 38-fold (p<0.0001). At least for certain patients, e.g., infants receiving large volume transfusions and patients in liver failure, it may be advisable to use RBCs as fresh as possible and to limit infusion (by VR or washing) of ammonia in the supernatant.
Asunto(s)
Conservación de la Sangre/métodos , Transfusión de Eritrocitos/efectos adversos , Eritrocitos , Hiperamonemia/prevención & control , Amoníaco/sangre , Transfusión de Eritrocitos/métodos , Humanos , Hiperamonemia/etiologíaRESUMEN
In a patient with suspected lymphoma, it is considered desirable to confirm the diagnosis by excisional biopsy of enlarged lymph nodes. However, sometimes the ideal nodes are positioned internally, requiring a deep invasive procedure for access, or the patient may have underlying medical conditions that make it risky to perform such an invasive procedure. Under a protocol approved by our institution's review board (IRB), we reviewed five patients in whom superficial lymph nodes were biopsied which were smaller than usually considered optimal for diagnosis (=2 cm). In each of these cases, the biopsy yielded diagnostic information upon which treatment could be based, sparing the patient a deep invasive procedure. We suggest that in situations in which large internal lymph nodes are not easily accessible and/or the patient's clinical situation precludes more invasive procedures, including deep core needle biopsy of a large mass, it is worthwhile to consider the removal of smaller, superficial lymph nodes with minimal risk which may suffice for diagnosis.
Asunto(s)
Biopsia con Aguja/métodos , Ganglios Linfáticos/patología , Linfoma/diagnóstico , Linfoma/patología , Adulto , Anciano , Histocitoquímica , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los ÓrganosAsunto(s)
ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Proteínas Portadoras/metabolismo , ADN Helicasas/metabolismo , Reticulocitos/metabolismo , ATPasas Asociadas con Actividades Celulares Diversas/inmunología , Western Blotting , Proteínas Portadoras/inmunología , Citoplasma/metabolismo , ADN Helicasas/inmunología , Eritrocitos/citología , Eritrocitos/metabolismo , Enfermedades Hematológicas/metabolismo , Enfermedades Hematológicas/patología , Humanos , Inmunohistoquímica , Reticulocitos/citologíaAsunto(s)
Púrpura Trombocitopénica Idiopática/diagnóstico , Autoanticuerpos/inmunología , Recuento de Células Sanguíneas , Plaquetas/inmunología , Enfermedad Crónica , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/inmunologíaRESUMEN
BACKGROUND: Patients who receive heart transplants may undergo therapeutic plasma exchange to reduce high levels of HLA antibodies which may increase the risk of allograft rejection. Plasma exchange may predispose to hypocalcemia because of chelation of calcium by sodium citrate, used as an anticoagulant both during the procedure and in thawed fresh frozen plasma often used for replacement. METHODS: We report three adults with dilated cardiomyopathy who underwent cardiac transplantation and serial plasma exchange for high levels of HLA antibodies. We followed these patients' pre-exchange serum calcium levels and the quantity of calcium supplementation they received. Further, we examined myocardial tissue sections post-transplantation for calcium deposition. RESULTS: Our patients' serum calcium levels were initially normal, but, despite aggressive calcium repletion, remained low (nadirs for pre-exchange ionized calcium in two patients 4.48 and 3.8mg/dL, respectively, reference range 4.6-5.4mg/dL). For patient 3, pre-exchange total calcium on day 2 was 7.9mg/dL (reference range 8.4-10.2mg/dL). Two patients had intermittent symptoms of hypocalcemia. Studies of cardiac tissue sections (available only from these two patients) were consistent with the presence of calcium deposition post transplantation. In comparison, six patients who underwent lung transplantation and plasma exchange for high levels of HLA antibodies did not manifest significant hypocalcemia. CONCLUSIONS: We emphasize the need for prompt and sufficient calcium replacement, monitored by serum ionized calcium levels, in the early post-cardiac transplantation period when plasma exchange is performed with thawed fresh frozen plasma replacement. The persistently low serum calcium levels we observed post heart transplantation were possibly contributed to by increased myocardial calcium influx.
Asunto(s)
Autoanticuerpos/sangre , Rechazo de Injerto/prevención & control , Antígenos HLA , Trasplante de Corazón , Hipocalcemia/sangre , Hipocalcemia/terapia , Intercambio Plasmático , Anciano , Calcio/sangre , Cardiomiopatía Dilatada/sangre , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/cirugía , Femenino , Humanos , Hipocalcemia/patología , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Miocardio/patología , Factores de Tiempo , Trasplante HomólogoRESUMEN
We have previously reported that the human programmed cell death-2 gene (PDCD2), a target of BCL6 repression, is likely to be important in the pathogenesis of certain human lymphomas. We now demonstrate that transfection of a construct expressing PDCD2 induces apoptosis in human cell lines, that this occurs, at least in part, through activation of the caspase cascade, and, furthermore, that caspase inhibitors block this effect. Immunohistochemical studies in human benign lymphoid and lymphoma tissues support these findings. In addition, transfection of a VP16-BCL6 zinc fingers fusion protein, which competes with the binding of endogenous BCL6 in a Burkitt lymphoma cell line, increases PDCD2 protein expression and apoptosis, and knockdown of the PDCD2 protein in this cell line by PDCD2-specific small interfering RNA duplexes inhibits apoptosis. These studies indicate that one function of PDCD2 is to promote apoptosis in several human and mammalian cell lines and tissues, including lymphoma. Although the pathways involved in lymphomagenesis are likely to be multiple and complex, it is plausible that repression of PDCD2 expression by BCL6, which, in turn, leads to downregulation of apoptosis, is one mechanism involved in BCL6-associated lymphomatous transformation. The usefulness of increasing PDCD2 expression in the treatment of certain lymphomas merits further investigation.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Caspasa 3/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Linfoma/metabolismo , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Apoptosis , Proteínas Reguladoras de la Apoptosis/genética , Inhibidores de Caspasas , Humanos , Inmunohistoquímica , Células K562 , Riñón/citología , Linfoma/genética , Linfoma/inmunología , Proteínas Proto-Oncogénicas c-bcl-6/genética , ARN Interferente Pequeño/genética , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Dedos de ZincRESUMEN
We reported that the integral membrane 2B gene (ITM2B, also called BRI2) is a target of BCL6 repression in lymphomas. Molecular alterations in ITM2B are associated with 2 neurodegenerative diseases, Familial British and Danish dementia, and dysregulation of ITM2B function has been implicated in the pathogenesis of Alzheimer disease (AD). Although ITM2B expression has been studied, the distribution of BCL6 in human brain has not been described. Our goal is to analyze BCL6 and ITM2B localization in normal human brains and in AD by immunohistochemistry to understand their relationship. We found that, in general, they have a reciprocal relationship. BCL6 expression is present in isolated cortical neurons, granule cells in the cerebellum, scattered glial cells, and in some cells of the ependyma and choroid plexus. ITM2B is expressed in most cortical neurons, neurons of the hippocampus and dentate nucleus, cerebellar Purkinje and granule cells, and (newly described here) in focal neurons in the basal ganglia, many neurons of the thalamus and brainstem, many cells in the ependyma and choroid plexus, and in the smooth muscle of blood vessels. ITM2B expression is prominent in plaques in AD-containing dystrophic neurites but absent in neurofibrillary tangles; BCL6 expression is absent in neurofibrillary tangles and in the nuclei of cells associated with plaques in AD. It is essential to understand the localization of BCL6 and ITM2B in the brain before considering manipulation of their expression as a potential therapeutic tool.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Regulación de la Expresión Génica , Glicoproteínas de Membrana/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-6/biosíntesis , Proteínas Adaptadoras Transductoras de Señales , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Encéfalo/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The human BCL6 gene, which is involved in the pathogenesis of certain human lymphomas, encodes a transcriptional repressor that is needed for germinal center B cell development and T follicular helper cell differentiation. Our goal was to identify BCL6 target genes using a cell system in which BCL6 repressive effects are inhibited followed by subtractive hybridization, and we detected the RUVBL1 (Pontin, TIP49) gene as a potential target of BCL6 repression. Here we show that the BCL6 protein significantly represses RUVBL1 transcription (6.8-fold). Knockdown of endogenous BCL6 in a human B cell lymphoma line leads to significant upregulation of RUVBL1, and there is an inverse expression pattern between the BCL6 and RUVBL1 proteins in certain human lymphomas. RUVBL1 is part of the AAA+ superfamily and participates in multiple processes, including gene transcription regulation, chromatin remodeling, and DNA repair, which, if dysregulated, may promote lymphoma development. A further understanding of the relationship between RUVBL1 and BCL6 should improve our understanding of the pathogenesis of human lymphomas.
RESUMEN
The thrombotic thrombocytopenic purpura syndrome (TTP) can be mistaken for a number of other conditions, and it is important to diagnose correctly and treat appropriately. We describe the features of TTP that can help make a positive diagnosis and other conditions in the differential diagnosis with symptoms that can overlap and mimic those of TTR. We discuss TTP and its variants, hemolytic uremic syndrome, disseminated intravascular coagulation, heparin-induced thrombocytopenia, antiphospholipid syndrome, Evans syndrome, preeclampsia/eclampsia, HELLP syndrome, acute fatty liver of pregnancy, and multiorgan failure.
Asunto(s)
Púrpura Trombocitopénica Trombótica , Diagnóstico Diferencial , Femenino , Humanos , Embarazo , Púrpura Trombocitopénica Trombótica/clasificación , Púrpura Trombocitopénica Trombótica/diagnóstico , Púrpura Trombocitopénica Trombótica/terapiaRESUMEN
We report the development of squamous cell carcinomas (SCCs) of the skin at or near the site of ear tags composed of a nickel-copper alloy and used for identification during the course of a long-term study of incipient congenic FVB/N mice containing the human BCL6 transgene (FVB.Cg-Tg[tetO-BCL6]Bbn Tg[EmicroSR-tTa]83Bop), their littermate controls, and wild-type FVB/N. Of a total population of 160 mice, 14 (8.8%) developed SCCs in the tagged (right) ear after a median observation period of 25 months, but none of the animals developed tumors in the opposite ear (P = 0.0001). Nine of the fourteen mice with SCCs had to be euthanized because they were thought to be in distress from the ear condition, but the remaining five died or were euthanized for other reasons related to the research study. These animals ranged in age from 331 to 921 days at the time of death. Five of the tumors were well-differentiated (grade 1) SCCs; the remainder were grade 3 and tended to be deeply invasive neoplasms with undifferentiated areas containing a spindle cell component. One of these metastasized to kidney. When using the FVB/N mouse strain for long-term studies, it is necessary to consider that nearly 9% of the population may develop SCCs at or near ear-tag sites that may necessitate early removal of the animal.
Asunto(s)
Envejecimiento/patología , Aleaciones/toxicidad , Sistemas de Identificación Animal , Carcinoma de Células Escamosas/inducido químicamente , Oído Externo , Neoplasias Cutáneas/inducido químicamente , Animales , Carcinoma de Células Escamosas/secundario , Cobre , Oído Externo/patología , Ratones , Ratones Endogámicos , Ratones Transgénicos , Níquel , Neoplasias Cutáneas/patologíaRESUMEN
Lipoprotein X (LpX) is an abnormal lipoprotein found in conditions such as lecithin:cholesterol acyltransferase deficiency and cholestatic states (e.g., primary biliary cirrhosis and primary sclerosing cholangitis). Management of severe hypercholesterolemia due to LpX with drugs and physical removal methods is not well established in the literature. A case is discussed of a 51-year-old woman who presented with multiple electrolyte abnormalities, xanthomas and neuropathy found to be secondary to LpX in the setting of primary sclerosing cholangitis. This case highlights that oral medications, including statins, may be insufficient to normalize lipid levels or improve clinical symptoms of LpX and presents therapeutic plasma exchange as a safe and effective therapeutic option to treat the morbid sequela of LpX hyperlipidemia.
RESUMEN
The growing interest in scientometry stems from ethical concerns related to the proper evaluation of scientific contributions of an author working in a hard science. In the absence of a consensus, institutions may use arbitrary methods for evaluating scientists for employment and promotion. There are several indices in use that attempt to establish the most appropriate and suggestive position of any scientist in the field he/she works in. A scientist's Hirsch-index (h-index) quantifies their total effective published output, but h-index summarizes the total value of their published work without regard to their contribution to each publication. Consequently, articles where the author was a primary contributor carry the same weight as articles where the author played a minor role. Thus, we propose an updated h-index named Hirsch(p,t)-index that informs about both total scientific output and output where the author played a primary role. Our measure, h(p,t) = h(p),h(t), is composed of the h-index h(t) and the h-index calculated for articles where the author was a key contributor; i.e. first/shared first or senior or corresponding author. Thus, a h(p,t) = 5,10 would mean that the author has 5 articles as first, shared first, senior or corresponding author with at least 5 citations each, and 10 total articles with at least 10 citations each. This index can be applied in biomedical disciplines and in all areas where the first and last position on an article are the most important. Although other indexes, such as r- and w-indexes, were proposed for measuring the authors output based on the position of researchers within the published articles, our simpler strategy uses the already established algorithms for h-index calculation and may be more practical to implement.