Cost-effectiveness of the regimen proposed by the International Consortium on Acute Promyelocytic Leukemia for the treatment of newly diagnosed patients with Acute Promyelocytic Leukemia

ABSTRACT Introduction: We performed cost-effectiveness and cost-utility analyses of the modified International Consortium on Acute Promyelocytic Leukemia protocol in Mexico for the treatment of acute promyelocytic leukemia Acute Promyelocytic Leukemia. Methods: We performed a three-state Markov analysis: stable disease (first line complete response [CR]), disease event (relapse, second line response and CR) and death. The modified IC-APL protocol is composed of three phases: induction, consolidation and maintenance. Cost and outcomes were used to calculate incremental cost-effectiveness ratios (ICERs); quality-adjusted life-years were used to calculate incremental cost-utility ratios (ICURs). Results: The CR was achieved in 18 patients (90%), treated with the IC-APL protocol as the first-line option; one patient (5%) died in induction, another one never achieved CR (5%); of the 18 patients that achieved CR, 1 relapsed (5.5%). The median treatment cost of the IC-APL protocol was $21,523 USD. The average life-year in our study was 7.8 years, while the average quality-adjusted life-year (QALY) was 6.1 years. When comparing the ICER between the IC-APL and the all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) protocols, we found the different costs of $6497, $19,133 and $17,123 USD in Italy, the USA and Canada, respectively. In relation to the ICUR, we found the different costs to be $13,955 and $11,979 USD in the USA and Canada, respectively. Conclusion: Taking into account the similar response rates, lower cost and easy access to the modified IC-APL regimen, we consider it a cost-effective and cost-utility protocol, deeming it the treatment of choice for our population.

Cost-effectiveness of the regimen proposed by the International Consortium on Acute Promyelocytic Leukemia for the treatment of newly diagnosed patients with Acute Promyelocytic Leukemia.

INTRODUCTION: We performed cost-effectiveness and cost-utility analyses of the modified International Consortium on Acute Promyelocytic Leukemia protocol in Mexico for the treatment of acute promyelocytic leukemia Acute Promyelocytic Leukemia. METHODS: We performed a three-state Markov analysis: stable disease (first line complete response [CR]), disease event (relapse, second line response and CR) and death. The modified IC-APL protocol is composed of three phases: induction, consolidation and maintenance. Cost and outcomes were used to calculate incremental cost-effectiveness ratios (ICERs); quality-adjusted life-years were used to calculate incremental cost-utility ratios (ICURs). RESULTS: The CR was achieved in 18 patients (90%), treated with the IC-APL protocol as the first-line option; one patient (5%) died in induction, another one never achieved CR (5%); of the 18 patients that achieved CR, 1 relapsed (5.5%). The median treatment cost of the IC-APL protocol was $21,523 USD. The average life-year in our study was 7.8 years, while the average quality-adjusted life-year (QALY) was 6.1 years. When comparing the ICER between the IC-APL and the all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) protocols, we found the different costs of $6497, $19,133 and $17,123 USD in Italy, the USA and Canada, respectively. In relation to the ICUR, we found the different costs to be $13,955 and $11,979 USD in the USA and Canada, respectively. CONCLUSION: Taking into account the similar response rates, lower cost and easy access to the modified IC-APL regimen, we consider it a cost-effective and cost-utility protocol, deeming it the treatment of choice for our population.

Role of vitamin C in diabetic ketoacidosis: Is it ready for prime time?

Diabetic ketoacidosis (DKA) is life-threatening acute metabolic complication of diabetes mellitus (DM) that is characterized by acidosis, ketosis, and hyperglycemia, currently affecting mostly patients under 30 years of age with diabetes mellitus type 1. In both, DM and DKA, a pro-inflammatory state exists. This clinical entity occurs as a result of hyperglycemia-induced disturbances, resulting in an increased oxidative metabolism. For the latter reason, the use of vitamin C seems promising in DKA due to its antioxidant role in reducing the superoxide radicals that are consequence of the oxidative stress. This can decrease the pro-inflammatory state and avoids complications. Vitamin C, or also known as ascorbic acid, has been widely used in several illnesses, such as common cold, tissue healing, fertility, atherosclerosis, cancer prevention, immunity restoration, neuro-degenerative disease and also has been suggested to decrease the risk of DM, and this reason is giving place to believe that vitamin C can have an important role in treating diabetic complications such as DKA. In order to counteract these oxidative disturbances in DKA patients, we analyzed the current data regarding vitamin C and evaluate its role in any type treatment of this complication in the near future.

Splenic myeloid metaplasia in warm autoimmune hemolytic anemia (wAIHA): a retrospective study.

BACKGROUND: Splenic myeloid metaplasia (SMM) is a kind of extramedullary hematopoiesis, whereas its clinical significance in wAIHA remains unclear. The aim of this study is evaluating the frequency and clinical characteristics of SMM, compared with splenic-congestion (SC). METHODS: We included patients with wAIHA treated in a Mexican tertiary hospital between January 1992 and December 2015. All patients received steroids as first-line treatment and splenectomy as second-line treatment. RESULTS: Among the thirty-six splenectomized patients, 15 (41.6%) and 21 (58.4%) were diagnosed as SMM and SC, respectively. No differences were found in clinical characteristics between two groups. SMM patients showed lower platelet count (147×109/L vs. 240×109/L, P=0.02) and higher presence of anti-dsDNA antibodies (40% vs. 4.7%, P=0.01) than SC patients. Although the complete response (CR) rate with first-line treatment was lower in SMM patients (13.3% vs. 47.6%; P=0.04), post-splenectomy median disease-free-survival (DFS) was longer (16.2 mo vs. 5.1 mo; P=0.19). Univariate/multivariate analysis showed that achieving CR during first-line treatment (OR 0.3, 95% CI: 0.03-0.94, P=0.03) and higher platelet count (OR 0.99, 95% CI: 0.98-0.99, P=0.03) were protective factors for SMM; and anti-dsDNA titer higher than 9.6 IU/dL was a risk factor for SMM (OR 2.76, 95% CI: 1.48-5.14, P<0.001). CONCLUSION: The wAIHA patients with SMM have different biological profiles with those without SMM. This study is the first trial evaluating the significance of histopathological spleen findings and their association with rheumatologic profile.

Importance of CD117 in the Assignation of a Myeloid Lineage in Acute Leukemias.

The correct classification of acute leukemias (AL) is an essential part in the evaluation of any patient with this disease. Historically, CD117 has been an important asset in the diagnosis of patients with mixed-phenotype acute leukemia (MPAL). In an attempt to simplify the diagnosis of MPAL with fewer and more lineage specific markers, the World Health Organization (WHO) proposed in 2008 a new criteria for the diagnosis of this type of AL, which excluded CD117 from the myeloid markers that are utilized to diagnose MPAL. In order to assess whether CD117 is necessary in the diagnosis of MPAL, we evaluated the sensitivity and specificity of CD117 for acute myeloid leukemia (AML) in 331 patients with AL. The calculated sensitivity of CD117 for AML was 85.88% (103/120), while the specificity was 83.9% (177/211). Besides myeloperoxidase (MPO), which was used as the gold standard in differentiating AML from other type of ALs, the most specific markers for AML in our study were CD14 and CD64 (99.5 and 95.6%). Although the specificity of CD117 in this study is not as high as CD14 and CD64, markers concomitantly used in this this study and in the WHO classification, based on the results of other researches (i.e. the specificity of CD117 for AML was 100% in one study) and due to the fact that its specificity for AML in this study is relatively high, we recommend the use CD117 in assigning a myeloid lineage in MPAL.

Possible role of intronic polymorphisms in the PHACTR1 gene on the development of cardiovascular disease.

Cardiovascular disease (CVD) is a complex multifactorial and polygenetic disease in which the interaction of numerous genes, genetic variants, and environmental factors plays a major role in its development. In an attempt to demonstrate the association between certain genetic variants and CVD, researchers have run large genomic wild association studies (GWAS) in recent decades. These studies have correlated several genomic variants with the presence of CVD. Recently, certain polymorphisms in the phosphatase and actin regulator 1 (PHACTR1) gene have been shown to be associated with CVD (i.e., coronary artery disease, coronary artery calcification, early onset myocardial infarction, cervical artery dissection and hypertension) in different ethnic groups. It is important to state that all of the described PHACTR1 genetic variants associated with CVD are located in non-translating gene regions known as introns. Thus, the purpose of this article is to hypothesize the effect of certain intronic polymorphisms in the PHACTR1 gene on pathological processes in the cardiovascular system. In addition, we present compelling evidence that supports this hypothesis as well as a methodology that could be used to assess the allelic effect using in vitro and in vivo models, which will ultimately demonstrate the pathophysiological contribution of PHACTR1 intronic polymorphisms to the development of CVD.

Expression of HER2/Neu in B-Cell Acute Lymphoblastic Leukemia.

BACKGROUND: The expression of HER2/neu in B-cell acute lymphoblastic leukemia has been reported in previous studies. OBJECTIVE: The objective of this research was to study the expression of HER2/neu on the blasts of patients with acute leukemia from the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. METHODS: From June 2015 to February 2016, a HER2/neu monoclonal antibody was added to the panel of antibodies that we routinely use in patients with acute leukemia. An expression of ≥ 30% was considered positive. RESULTS: We studied 33 patients: 19 had de novo leukemia (57.6%), three (9.1%) were in relapse, and in 11 (33.3%) their status could not be specified. Seventeen patients (51.5%) were classified as B-cell acute lymphoblastic leukemia with a median expression of HER2/neu of 0.3% (range 0-90.2). Three patients with B-cell acute lymphoblastic leukemia were positive for HER2/neu: 89.4%, 90.9%, and 62.4%. The first and third patient had de novo B-cell acute lymphoblastic leukemia. The second patient was in second relapse after allogeneic stem cell transplant. All three patients were categorized as high-risk at the time of diagnosis. CONCLUSIONS: In the studied Mexican population, we found a positive expression of HER2/neu in 17% of the B-cell acute lymphoblastic leukemia patients, similar to previous studies in which the expression was found in 15-50%.

Atypical Proliferating Trichilemmal Cyst with Malignant Breast Skin Transformation: A Case Report and Review of the Literature.

Proliferating trichilemmal tumors (PTTs) are benign adnexal skin neoplasms that arise from the outer root sheath of the hair follicle. These tumors are most commonly observed on the scalp and occur, most of the time, in elderly women. Malignant transformation of these neoplasms is a rare event; less than 50 cases have been reported in the English medical literature. We present the case of a 39-year-old Hispanic woman with a tumor located on the skin of one of her breasts that in her third surgical procedure the histologic examination revealed the presence of a malignant proliferating trichilemmal tumor (MPTT). Furthermore, a review of the medical literature and a discussion of the clinical and pathologic features of this rare entity are provided.

[Protein supplement consumption and its possible association with kidney damage in Mexican elite athletes]. / Consumo de suplemento proteico y su posible asociación con daño renal en atletas mexicanos de alto rendimiento.

BACKGROUND: Protein supplements are one of the most used ergogenic supplements by elite athletes. Nonetheless, it has been postulated that the use of these type of supplements may cause chronic renal failure. The objective of this study is to analyze the effects of the consumption of protein supplements in the renal function of elite athletes of the Mexican Olympic Training Center. METHODS: 74 athletes provided urine samples in order to quantify urinary proteins. Some of them were excluded since they had conditions that could cause proteinuria or alter the quality of the samples. Those that were not excluded were divided into two groups: the experimental group, which included those individuals that had the antecedent of consuming protein supplements, and the control group, that encompassed those individuals that did not had the antecedent of consuming protein supplements. RESULTS: Of the 74 analyzed athletes, 44 were excluded, 11 individuals were included in the experimental group, and 19 in the control group. Microproteinuria was encountered in only one urine sample (control group), and it was determined that there was no significant differences between both groups. CONCLUSION: From the gathered results it can be concluded that protein supplements do not affect renal function. Nonetheless, in the future protein supplements should be evaluated in groups with pathologies or conditions that may compromise renal function.

Introducción: los suplementos proteicos son unos de los suplementos ergogénicos más utilizados por los atletas de alto rendimiento. Sin embargo, se ha postulado que el consumo de estos pudiese ser causa de insuficiencia renal crónica. El objetivo fue analizar los efectos del consumo de suplementos proteínicos en la función renal de los atletas de alto rendimiento del Centro Deportivo Olímpico Mexicano. Métodos: se evaluaron 74 atletas, en cuya muestra de orina se cuantificaron las proteínas. Se excluyeron los atletas con antecedentes o condiciones que pudiesen causar proteinuria o que pudieran alterar la calidad de la muestra. Los elegidos se dividieron en dos grupos con base en el antecedente de consumo de suplemento proteico: el grupo experimental lo conformaron los consumidores y el control los no consumidores. Resultados: de 74 atletas analizados, 44 fueron excluidos, 11 se incluyeron al grupo experimental y 19 al grupo control. Se obtuvo un resultado positivo para microproteinuria en este último grupo. Se determinó estadísticamente que ambos grupos eran similares y se estableció, en relación con el resultado positivo de microproteinura, que no existe una diferencia significativa entre ambos grupos. Conclusión: el consumo de suplemento proteico no ha afectado la función renal de los atletas analizados. Pese a esto, consideramos que la seguridad del suplemento proteico debe ser evaluada en un futuro en ciertos grupos con patologías o antecedentes que pudieran comprometer la función renal.

Mixed-phenotype acute leukemia: suboptimal treatment when the 2008/2016 WHO classification is used.

BACKGROUND: Different criteria have been used to diagnose mixed-phenotype acute leukemia (MPAL), which has impacted the number of individuals diagnosed with this pathology. Better outcomes have been reported when using acute lymphoblastic leukemia (ALL)-type chemotherapy in the treatment of MPAL. METHODS: We compared the outcome of 4 groups of patients with MPAL. Group 1 included patients diagnosed using the 2008/2016 World Health Organization (WHO) classification; group 2 included patients diagnosed using the European Group for the Immunological Characterization of Leukemias (EGIL) criteria; group 3 included patients diagnosed using either the EGIL or the 2008/2016 WHO criteria; and group 4 was comprised of patients diagnosed with MPAL using the EGIL classification only. RESULTS: We found a significantly worse disease-free survival (groups 1-4) and overall survival (OS) (groups 2 and 3) when comparing MPAL patients to other acute leukemia (AL) patients. A significantly better OS was obtained in patients (groups 2-4) treated with ALL-type chemotherapy compared to acute myeloid leukemia (AML)-type regimens. CONCLUSION: In light of these results, and because a trend (P=0.06) was found with regard to a better OS in group 4 when compared to other AL patients, an argument can be made that the 2008/2016 WHO classification is underpowered to diagnose all MPAL cases, potentially resulting in the suboptimal treatment of some individuals with AL.

Impact of Aberrant Antigens in the Outcome of Patients with Acute Leukemia at a Referral Institution in Mexico City.

BACKGROUND: Patients with acute leukemia can express aberrant markers, defined as antigens that are normally restricted to a different lineage. The reported significance and frequency of these markers is inconclusive. We assessed the frequency and impact of aberrant markers in patients with acute leukemia in a referral institution in Mexico City. METHODS: We included 433 patients, diagnosed and treated between 2005 and 2015 in our institution. RESULTS: Aberrant markers were expressed in 128 patients (29.6%); CD13 and CD33 were the most frequent aberrant markers in patients with acute lymphoblastic leukemia, while CD7 and CD19 were the most frequent in patients with acute myeloid leukemia. In the univariate analysis, the group with aberrant markers had a lower disease-free survival when compared with the aberrant-free group (8 vs. 13 months) (p = 0.03). Aberrant expression of CD10, CD20, and CD33 correlated with a worse outcome in a statistically significant manner. In the multivariate analysis, male gender, lymphoid lineage, secondary leukemia, high risk at diagnosis, and the presence of aberrant markers had a significantly negative impact on disease-free survival. CONCLUSION: The use of more aggressive treatment strategies could be considered in patients with acute leukemia and an aberrant expression of CD10, CD20, and CD33.

Síndrome de Wiskott-Aldrich: Caso clínico / Wiskott-Aldrich syndrome: Case report

El síndrome de Wiskott-Aldrich es una inmunodeficiencia primaria; con una incidencia de 3,5 a 5,2 por cada millón de recién nacidos masculinos. Se caracteriza por tener un patrón de herencia recesiva ligada al cromosoma X. En estos pacientes; se ha descrito la tríada clásica de inmunodeficiencia; microtrombocitopenia y eczema. Presentamos un paciente de 5 años de edad; hispánico; con antecedentes de numerosas infecciones desde el primer año de vida. Actualmente; presenta desnutrición crónica; talla baja secundaria y retraso en el desarrollo del lenguaje. Se diagnosticó una mutación poco frecuente del gen asociado al síndrome de Wiskott-Aldrich.

The Wiskott-Aldrich syndrome is a rare X-linked recessive immunodeficiency, with an estimated incidence of 3.5 to 5.2 cases per million males. It is characterizedby immunodeficiency, microthrombocytopenia and eczema. We present a 5-year-old Hispanic male, with a medical history of numerous infectious diseases, compromised health, chronic malnutrition, language delay and failure to thrive. An infrequent mutation in the Wiskott-Aldrich syndrome gene was found.

Síndrome de Wiskott-Aldrich: Caso clínico / Wiskott-Aldrich syndrome: Case report

El síndrome de Wiskott-Aldrich es una inmunodeficiencia primaria; con una incidencia de 3,5 a 5,2 por cada millón de recién nacidos masculinos. Se caracteriza por tener un patrón de herencia recesiva ligada al cromosoma X. En estos pacientes; se ha descrito la tríada clásica de inmunodeficiencia; microtrombocitopenia y eczema. Presentamos un paciente de 5 años de edad; hispánico; con antecedentes de numerosas infecciones desde el primer año de vida. Actualmente; presenta desnutrición crónica; talla baja secundaria y retraso en el desarrollo del lenguaje. Se diagnosticó una mutación poco frecuente del gen asociado al síndrome de Wiskott-Aldrich.(AU)

The Wiskott-Aldrich syndrome is a rare X-linked recessive immunodeficiency, with an estimated incidence of 3.5 to 5.2 cases per million males. It is characterizedby immunodeficiency, microthrombocytopenia and eczema. We present a 5-year-old Hispanic male, with a medical history of numerous infectious diseases, compromised health, chronic malnutrition, language delay and failure to thrive. An infrequent mutation in the Wiskott-Aldrich syndrome gene was found.(AU)

The possibility of inventing new technologies in the detection of cancer by applying elements of the canine olfactory apparatus.

In order to find better tools in the diagnosis of cancer in an earlier and more precise manner, researchers have explored the use of volatile organic compound (VOCs) as a way to detect this disease. Interestingly, the canine olfactory apparatus was observed to detect cancer in two anecdotal reports. After the description of these events, researchers began to study this phenomenon in a structured way in order to assess the ability of canines in detecting cancer-related VOCs. Due to the fact that some of these studies have shown that the canine olfactory apparatus is highly proficient in the detection of cancer-related VOCs, in this article we assess the possibility of constructing a bioelectronic-nose, based on canine olfactory receptors (ORs), for the purpose of diagnosing cancer in a more sensitive, specific, and cost effective manner than what is available nowadays. Furthermore, in order to prove the feasibility and the need of the proposed apparatus, we searched for the following type of articles: all of the studies that have examined, to our knowledge, the ability of dogs in detecting cancer; articles that assess the dog olfactory receptor (OR) gene repertoire, since a central part of the proposed bioelectronic nose is being able to recognize the odorant that emanates from the cancerous lesion, and for that purpose is necessary to express the canine ORs in heterologous cells; examples of articles that depict different devices that have been built for the purpose of detecting cancer-related VOCs, so as to assess if the construction of the proposed apparatus is needed; and articles that describe examples of already constructed bioelectronic noses, in order to demonstrate the existence of a technical precedent and thus the plausibility of the proposed device.

[Wiskott-Aldrich syndrome: Case report]. / Síndrome de Wiskott-Aldrich: Caso clínico.

The Wiskott-Aldrich syndrome is a rare X-linked recessive immunodeficiency, with an estimated incidence of 3.5 to 5.2 cases per million males. It is characterized by immunodeficiency, microthrombocytopenia and eczema. We present a 5-year-old Hispanic male, with a medical history of numerous infectious diseases, compromised health, chronic malnutrition, language delay and failure to thrive. An infrequent mutation in the Wiskott-Aldrich syndrome gene was found.