Are delays in diagnosis and treatment of acute leukemia in a middle-income country associated with poor outcomes? A retrospective cohort study.

INTRODUCTION: Acute leukemias (ALs) are aggressive diseases that lead to death without medical attention. We evaluated the association between delays in diagnosis and poor outcomes in AL by evaluating the symptom onset to treatment intervals in adults with newly diagnosed AL and their effect on an early death (ED). METHODS: We assessed adults diagnosed with AL between 2015 and 2020 and evaluated baseline characteristics, the patient interval (PI), diagnostic interval (DI), treatment interval (TI) and the total time interval (TTI) to determine ED-associated factors. MAIN RESULTS: We assessed 102 patients with acute lymphoblastic leukemia (ALL), 57 with acute myeloblastic leukemia (AML) and 29 with acute promyelocytic leukemia (APL). Median interval days were PI 14, DI 10, TI 4 and TTI 31.5. The TI and TTI intervals were lower in APL than in ALL and AML; TI 1 vs. 4 and 3 (p = 0.001) and TTI 21 vs. 31 and 35 (p = 0.016). The 30-day and 60-day EDs were 13.8% and 20.7%, mainly infections. ECOG > 2 (OR = 15.0) and PI < 7 days (OR = 4.06) were associated with 30-day ED; AML (OR = 2.69), high-risk (OR = 3.34), albumin < 3.5 g/dl (OR = 5) and platelets < 20 × 103/uL (OR = 2.71) with a 60-day ED. CONCLUSION: None of the interval-delays were associated with an ED. Intervals seemed to be longer in patients without an ED, except for the TI, probably because of "the waiting time paradox." Aggressive manifestations of disease may lead to shorter diagnostic intervals, but increased mortality.

Clinical presentation in thrombotic thrombocytopenic purpura: Real-world data from two Mexican institutions.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease that can be fatal if not treated early. We aimed to describe the clinical characteristics of Mexican patients with idiopathic TTP. STUDY DESIGN AND METHODS: We conducted a retrospective study, including all adult patients diagnosed with idiopathic TTP from 2011 to 2017 in two Mexican centers. We further compared our results with the published literature. RESULTS: Twenty patients were included; 70% were female, with a median age of 38.5 years at diagnosis (range 16-63). The median time from onset of symptoms to hospital admission was 1.5 days (range 0-16). Most patients (85%) presented with at least one systemic manifestation at admission (including fever) and 90% had neurological symptoms, most of them major (70%) including loss of consciousness, transient focal abnormalities, headache, and confusion. Only one patient (5%) had the classical pentad at the time of admission. Kidney failure was present in 25% of patients and hemorrhagic symptoms in 60%. Digestive and cardiorespiratory symptoms were less common (45% and 15%, respectively). Median platelet count and lactate dehydrogenase were 10 500/µL and 1319 IU/L, respectively. Eighty percent of patients achieved remission following treatment. Patients admitted within the first 48 hours (after the onset of symptoms) tended to have better overall survival. CONCLUSION: Clinical presentation in Mexican TTP patients is similar to that in other countries. Early admission and a high suspicion for the disease will avoid delays in the initial work-up and initiation of therapy, further improving prognosis.

Iron deficiency anemia referral to the hematologist. Real-world data from Mexico: the need for targeted teaching in primary care.

OBJECTIVES: To determine the referral patterns and etiology of iron deficiency anemia (IDA) at an academic hematology center in northeast Mexico. METHODS: We included all consecutive outpatients older than 16 years, non-pregnant, with IDA diagnosed in the Hematology Service of the Dr. José E. González University Hospital between January 2012 and May 2017. Appropriate data were collected retrospectively from the electronic medical record. Data regarding first medical contact (primary care physician or hematologist) were compared. RESULTS: One hundred fifty-three patients were included in this study. The median age was 43 years (interquartile range, 35-51) and 85.6% were female; 128 (83.7%) patients were seen by a primary care physician before our evaluation. Abnormal uterine bleeding (AUB) was the cause of IDA in 76 patients (49.6%), gastrointestinal bleeding (GIB) in 31 (20.2%), H. pylori infection in 12 (7.8%), urinary tract bleeding in three (1.9%) and malabsorption-syndrome in two (1.3%). The etiology remained unknown in 29 (18.9%). The p value was <0.05 between groups according to the first medical contact, including frequency of at least one sign or symptom of IDA, previous use of iron supplementation and blood transfusion, comorbidities, complete blood count at diagnosis, and resolution rates of anemia. CONCLUSION: The majority of our IDA patients were referred by another physician. Nearly half of the patients with IDA had AUB. IDA remains a diagnostic challenge for first contact physicians requiring a targeted educational intervention to improve IDA awareness and diagnostic skills.

Danazol as First-Line Therapy for Myelodysplastic Syndrome.

BACKGROUND: Allogeneic stem cell transplantation (ASCT) represents the only option with a potential cure rate of 30% to 50% in myelodysplastic syndrome (MDS); however, < 5% of patients are optimal candidates for this management. Therapeutic options are limited in patients unsuitable for ASCT. Evidence that androgens might be beneficial in MDS is controversial. We aimed to document the clinical outcomes of patients diagnosed with MDS treated with danazol as first-line therapy. PATIENTS AND METHODS: We retrospectively reviewed patients diagnosed in our center with MDS according to the World Health Organization 2008 criteria and treated with danazol between 2005 and 2015. Response was defined according to international working group criteria. RESULTS: We included 42 patients treated exclusively with danazol. Median dose was 400 mg/d (range, 100-600 mg/d). Median follow-up was 12 (range, 3-76) months. Twenty-four of these patients (60%) achieved clinical response. Median overall survival was 24 months (95% confidence interval, 5.1-42). Responders were older than nonresponders (P = .025) and had higher baseline hemoglobin concentration (P = .009). No patients discontinued danazol because of toxicity. Fifteen patients died (35.7%) and 5 progressed to acute myeloid leukemia. CONCLUSION: Danazol as first-line therapy is an acceptable treatment option with low side effects for patients with MDS who cannot receive ASCT.

Estudio comparativo de dos métodos para la determinación de autoanticuerpos en hepatitis autoinmune / Comparative study of two methods in the determination of autoantibodies in autoimmune liver diseases / Estudo comparativo de dois métodos para a determinaþÒo de anticorpos no hepatite auto-imune

La hepatitis autoinmune es una inflamación hepatocelular que se caracteriza por diversos autoanticuerpos circulantes. En el presente trabajo se evaluó la concordancia entre los resultados obtenidos por la técnica ELISA y por la técnica de inmunofluorescencia indirecta (IFI) para la determinación de autoanticuerpos en hepatitis autoinmune. Se incluyeron 123 pacientes con hepatitis autoinmune, 91 (74%) del sexo femenino y 32 (26%) de sexo masculino, mayores de 18 años, en los cuales se realizó un estudio comparativo entre ELISA e inmunofluorescencia indirecta para la detección de los anticuerpos antinucleares (78 pacientes), anticuerpos antimitocondriales (84 pacientes) y antimicrosoma hepatorrenal (85 pacientes). De acuerdo al valor kappa obtenido se encontró que para el anticuerpo antimicrosoma hepatorrenal el nivel de concordancia fue muy bueno (k=1,0, p<0,001); para el anticuerpo antinuclear el nivel de concordancia fue débil, sin embargo fue significativo (k=0,37, p<0,001) mientras que para el anticuerpo antimitocondrial el nivel de concordancia fue pobre (k=0,05, p<0,476). La determinación del anticuerpo antimicrosoma hepatorrenal fue la prueba con mayor sensibilidad, especificidad y concordancia entre ambas técnicas analizadas y se estableció que la técnica de ELISA para el anticuerpo antimitocondrial solo concuerda con la técnica de inmunofluorescencia indirecta en sujetos con títulos altos.(AU)

Autoimmune hepatitis is a hepatocellular inflammation which is characterized by different circulating autoantibodies. In this paper, the correlation between the results obtained by ELISA and indirect immunofluorescence technique for the determination of autoantibodies in autoimmune hepatitis was evaluated. One hundred and twenty-three patients with autoimmune hepatitis, 91 (74%) female and 32 (26%) male, over 18 years were included. In these patients, a comparative study between ELISA and indirect immunofluorescence detection of the antinuclear antibodies (78 patients), anti-mitochondrial antibodies (84 patients) and anti-liver kidney microsome (85 patients) was performed. According to the kappa value obtained, it was found that for anti-liver kidney microsome the level of agreement was very good (k=1.0, p<0.001) for antinuclear antibody, the level of concordance was weak but significant (k=0.37, p<0.001,) meanwhile antimitochondrial antibody level of concordance was poor (k=0.05, p<0.476).The determination of the antibody anti-liver kidney microsome was the test with greater sensitivity, specificity and concordance between the two techniques discussed and it was established that the ELISA technique for antimitochondrial antibody is only in concordance with the indirect immunofluorescence in patients with high titers.(AU)

A hepatite autoimune é uma inflamaþÒo hepatocelular, que se caracteriza pelos diferentes anticorpos circulantes. Neste trabalho foi avaliada a correlaþÒo entre os resultados obtidos através da técnica ELISA e da técnica de imunofluorescÛncia indireta (IFI) para a determinaþÒo de auto-anticorpos na hepatite auto-imune. Foram incluídos 123 pacientes com hepatite autoimune, 91 (74%) do sexo feminino e 32 (26%) do sexo masculino, maiores de 18 anos, nos quais foi realizado um estudo comparativo entre ELISA e ImunofluoresÛncia Indireta para a detecþÒo dos anticorpos antinucleares (78 pacientes), anticorpos antimitocondriais (84 pacientes) e antimicrossomal hepatorrenal (85 pacientes). De acordo ao valor kappa obtido, foi encontrado que para o anticorpo antimicrossomal hepatorrenal o nivel de concordÔncia foi muito bom (k=1,0, p<0,001); para o anticorpo antinuclear o nivel de concordÔncia foi fraco, porém foi significativo (k=0,37, p<0,001) enquanto que para o anticorpo antimitocondrial o nivel de concordÔncia foi pobre (k=0,05, p<0,476). A determinaþÒo do anticorpo antimicrossomal hepatorrenal foi o teste com maior sensibilidade, especificidade e concordÔncia entre ambas técnicas analisadas e se estabeleceu que a técnica de ELISA, para o anticorpo antimitocondrial, só concorda com a técnica de ImunofluorescÛncia Indireta em sujeitos com títulos altos.(AU)

Estudio comparativo de dos métodos para la determinación de autoanticuerpos en hepatitis autoinmune / Comparative study of two methods in the determination of autoantibodies in autoimmune liver diseases / Estudo comparativo de dois métodos para a determinação de anticorpos no hepatite auto-imune

La hepatitis autoinmune es una inflamación hepatocelular que se caracteriza por diversos autoanticuerpos circulantes. En el presente trabajo se evaluó la concordancia entre los resultados obtenidos por la técnica ELISA y por la técnica de inmunofluorescencia indirecta (IFI) para la determinación de autoanticuerpos en hepatitis autoinmune. Se incluyeron 123 pacientes con hepatitis autoinmune, 91 (74%) del sexo femenino y 32 (26%) de sexomasculino, mayores de 18 años, en los cuales se realizó un estudio comparativo entre ELISA e inmunofluorescencia indirecta para la detección de los anticuerpos antinucleares (78 pacientes), anticuerpos antimitocondriales (84pacientes) y antimicrosoma hepatorrenal (85 pacientes). De acuerdo al valor kappa obtenido se encontró que para el anticuerpo antimicrosoma hepatorrenalel nivel de concordancia fue muy bueno (k=1,0, p<0,001); para el anticuerpoantinuclear el nivel de concordancia fue débil, sin embargo fue significativo(k=0,37, p<0,001) mientras que para el anticuerpo antimitocondrialel nivel de concordancia fue pobre (k=0,05, p<0,476). La determinación del anticuerpo antimicrosoma hepatorrenal fue la prueba con mayor sensibilidad, especificidad y concordancia entre ambas técnicas analizadas y se estableció que la técnica de ELISA para el anticuerpo antimitocondrial solo concuerda con la técnica de inmunofluorescencia indirecta en sujetos con títulos altos.

Autoimmune hepatitis is a hepatocellular inflammation which is characterized by different circulating autoantibodies. In this paper, the correlation between the results obtained by ELISA and indirect immunofluorescence technique for the determination of autoantibodies in autoimmune hepatitis was evaluated. One hundred and twenty-three patients with autoimmune hepatitis, 91 (74%) female and 32 (26%) male, over 18 years were included. In these patients, a comparative study between ELISA and indirect immunofluorescence detection of the antinuclear antibodies (78 patients), anti-mitochondrial antibodies (84 patients) and anti-liver kidney microsome (85 patients) was performed. According to the kappa value obtained, it was found that for anti-liver kidney microsome the level of agreement was very good (k=1.0, p<0.001) for antinuclear antibody, the level of concordance was weak but significant (k=0.37, p<0.001,) meanwhile antimitochondrial antibody level of concordance was poor (k=0.05, p<0.476).The determination of the antibody anti-liver kidney microsome was the test with greater sensitivity, specificity and concordance between the two techniques discussed and it was established that the ELISA technique for antimitochondrial antibody is only in concordance with the indirect immunofluorescence in patients with high titers.

A hepatite autoimune é uma inflamação hepatocelular, que se caracteriza pelos diferentes anticorpos circulantes. Neste trabalho foi avaliada a correlação entre os resultados obtidos através da técnica ELISA e da técnica de imunofluorescência indireta (IFI) para a determinação de auto-anticorpos na hepatite auto-imune. Foram incluídos 123 pacientes com hepatite autoimune, 91 (74%) do sexo feminino e 32 (26%) do sexo masculino, maiores de 18 anos, nos quais foi realizado um estudo comparativo entre ELISA e Imunofluoresência Indireta para a detecção dos anticorpos antinucleares (78 pacientes), anticorpos antimitocondriais (84 pacientes) e antimicrossomal hepatorrenal (85 pacientes). De acordo ao valor kappa obtido, foi encontrado que para o anticorpo antimicrossomal hepatorrenal o nivel de concordância foi muito bom (k=1,0, p<0,001); para o anticorpo antinuclear o nivel de concordância foi fraco, porém foi significativo (k=0,37, p<0,001) enquanto que para o anticorpo antimitocondrial o nivel de concordância foi pobre (k=0,05, p<0,476). A determinação do anticorpo antimicrossomal hepatorrenal foi o teste com maior sensibilidade, especificidade e concordância entre ambas técnicas analisadas e se estabeleceu que a técnica de ELISA, para o anticorpo antimitocondrial, só concorda com a técnica de Imunofluorescência Indireta em sujeitos com títulos altos.