Mobilized and apheresis-collected endothelial progenitor cells with plerixafor.

BACKGROUND: Endothelial progenitor cells (EPCs) are immature cells able to proliferate and contribute to endothelial repair, vascular homeostasis, neovascularization, and angiogenesis. It therefore seems likely that circulating EPCs have therapeutic potential in ischemic and vascular diseases. In this study we evaluated the efficiency of EPC mobilization and collection by large volume leukapheresis in subjects with hematological diseases, treated with plerixafor in association with G-CSF. METHODS: Twenty-two patients with lymphoid malignancies underwent rHuG-CSF and plerixafor treatment followed by leukapheresis. Blood samples before and after treatment and apheresis liquid sample were taken and analyzed by flow cytometry in order to quantified EPC. RESULTS: The percentage of CD34+ cells and EPCs among circulating total nuclear cells (TNCs) increased significantly by approximately 2-fold and 3-fold, respectively, after plerixafor treatment. Consequently, the absolute number of CD34+ cells and EPCs were increased 4-fold after plerixafor treatment. The median PB concentration of EPCs before and after treatment were 0.77/µL (0.31-2.15) and 3.41/µL (1.78-4.54), respectively, P < .0001. The total EPCs collected per patient were 3.3×107 (0.8×107 -6.8×107 ). CONCLUSION: We have shown that plerixafor in combination with G-CSF allows the mobilization and collection of large amounts of EPCs along with CD34+ cells in lymphoid neoplasm patients. The possibility to collect and to store these cells could represent a promising therapeutic tool for the treatment of ischemic complications without the need of in vitro expansion.

Impact of Treatment Prior to Allogeneic Transplantation of Hematopoietic Stem Cells in Patients with Myelodysplastic Syndrome: Results of the Latin American Bone Marrow Transplant Registry.

It has been suggested that bridging therapy with intensive chemotherapy and/or hypomethylating agents followed by hematopoietic stem cell transplantation (HSCT) can be valuable in the treatment of patients with myelodysplastic syndromes (MDS). However, the influence of this approach on HSCT outcomes remains poorly defined. Therefore, our objective was to investigate the influence of treatment before HSCT in patients with MDS. We retrospectively analyzed data from the Latin American registry of 258 patients from 17 Latin American centers who underwent HSCT from 1988 to 2019. Our data showed that there was pre-HSCT. We detected no significant difference regarding the impact on overall survival of treated and untreated patients before HSCT. Despite these data, the type of previous treatment among treated patients showed a significant difference in overall survival. Treatment with hypomethylating agents together with pre-HSCT chemotherapy seems to result in better survival of the studied population. These data correspond to the first results obtained through cooperative work between various centers in Latin America comparing the different approaches to patients and reflecting their reality and challenges. Therefore, the selection of pretransplant bridge therapy should be analyzed and focus given primarily to those approaches that result in better survival of patients with MDS.

Autologous bone marrow-derived cells for venous leg ulcers treatment: a pilot study.

BACKGROUND: Chronic venous leg ulcers (VLUs) are a common problem in clinical practice and available treatments are not satisfactory. The use of adjuvant therapies in combination with lower limb compression may lead to improved healing rates. Chronic wounds are candidates for new strategies in the emergent field of regenerative medicine. Bone marrow-derived cells (BMDCs) contain cells and secrete cytokines known to participate in wound healing. Thus, BMDC therapy seems a logical strategy for the treatment of chronic wounds. Our objective was to evaluate feasibility, safety and initial clinical outcome of autologous BMDC therapy associated with standard treatment in patients with VLUs. METHODS: We conducted an open-label, single-arm, prospective pilot clinical trial in four patients with six chronic VLUs. The study protocol was approved by the institutional and national review boards and ethics committees. Bone marrow was harvest, processed and then administered by multiple injections into the ulcers. All patients received standard treatment and non-healing characteristics of the VLUs were confirmed at study entry. RESULTS: Ulcer size and wound pain evaluated 12 months after BMDC treatment were significantly reduced (P < 0.05). BMDC treatment was safe and well tolerated in long-term follow-up. DISCUSSION: Despite the low number of patients studied, our results showed that autologous BMDC treatment could be a useful, feasible and safe procedure to enhance ulcer healing. However, randomized controlled trials with more patients are needed to address this question and translate this approach into clinical practice.

Absolute monocyte count as a prognostic parameter in diffuse large B cell lymphoma.

Background Prognosis of patients with Diffuse Large B Cell Lymphoma (DLBCL) is highly variable, and despite the use of modern immunochemotherapy regimens, almost 50% of patients will eventually relapse. Standard risk models, like the International Prognostic Index or the Revised International Prognostic Index (R_IPI) incorporate patient and tumor characteristics but do not consider variables related to host adaptive immunity which have been shown to be of significant prognostic value in non-Hodgkin lymphomas. Aim To analyze the prognostic significance of the absolute monocyte count at diagnosis in diffuse large-B-cell lymphoma in a retrospective setting. Material and Methods We reviewed data of 171 patients with DLBCL treated with Rituximab-based immunochemotherapy at two reference public Hospitals in Montevideo-Uruguay. The outcome measures were overall and relapse free survival. Results The absolute monocyte count, analyzed as a dichotomized variable predicted progression-free and overall survival in low risk patients according to the R-IPI score. Worse outcomes were observed in those with high monocyte count al diagnosis. Conclusions Absolute monocyte count could help in the identification of high-risk patients otherwise expected to have a good prognosis according to traditional scores.

[Adult T-cell leukemia/lymphoma. Report of a case in Uruguay]. / Un caso de leucemia/linfoma T del adulto en Uruguay.

Adult T-cell leukemia/lymphoma belongs to the group of mature T-cell malignancies according to the WHO classification. It constitutes a rare entity and has a strong association with infection by human T-lymphotropic virus 1. In Uruguay, this viral infection is very infrequent and, to our knowledge, no case of adult T-cell leukemia/lymphoma has been previously reported. We describe the case of a woman, immigrant from Peru, who presented with persistent lymphocytosis, intestinal parasitic diseases, and skin involvement. The diagnosis was delayed and the patient died before initiating oncological treatment. We therefore emphasize the relevance of an early clinical suspicion and serology for this virus, especially in patients coming from endemic countries like Peru.

A new ß(0) frameshift mutation, HBB: c.44delT (p.Leu14ArgfsX5), identified in an Argentinean family associated with secondary genetic modifiers of ß-thalassemia.

ß-Thalassemia intermedia (ß-TI) patients present with a wide spectrum of phenotypes depending on the presence of primary, secondary, and tertiary genetic modifiers which modulate, by different mechanisms, the degree of imbalance between α and ß chains. Here we describe a new ß(0) frameshift mutation, HBB: c.44delT (p.Leu14ArgfsX5), identified in four members of a family, associated with secondary genetic modifiers in three of them. The different genotype present in this family was suspected after hematological analysis and thorough observation of blood smears highlighting their importance in the identification of ß-TI patients among members of the same family.

Comparative analysis of persistence and remission with guselkumab versus secukinumab and ixekizumab in the United States.

Purpose: Real-world data comparing long-term performance of interleukin (IL)-23 and IL-17 inhibitors in psoriasis are limited. This study compared treatment persistence and remission among patients initiating guselkumab versus IL-17 inhibitors.Methods: Adults with psoriasis initiating guselkumab, secukinumab, or ixekizumab treatment (index date) were identified from Merative™ MarketScan® Research Databases (01/01/2016-10/31/2021). Persistence was defined as no index biologic supply gaps of twice the labeled maintenance dosing interval. Remission was defined using an exploratory approach as index biologic discontinuation for ≥6 months without psoriasis-related inpatient admissions and treatments.Results: There were 3516 and 6066 patients in the guselkumab versus secukinumab comparison, and 3805 and 4674 patients in guselkumab versus ixekizumab comparison. At 18 months, the guselkumab cohort demonstrated about twice the persistence rate as secukinumab (hazard ratio [HR] = 2.15; p < 0.001) and ixekizumab cohorts (HR = 1.77; p < 0.001). At 6 months after index biologic discontinuation, the guselkumab cohort was 31% and 40% more likely to achieve remission than secukinumab (rate ratio [RR] = 1.31; p < 0.001) and ixekizumab cohorts (RR = 1.40; p < 0.001).Conclusions: Guselkumab was associated with greater persistence and likelihood of remission than IL-17 inhibitors, indicating greater disease control and modification potential.

Venous Thromboembolism Risk and Adherence to Pharmacological Thromboprophylaxis in Hospitalized Patients in Uruguay: First Nationwide Study.

INTRODUCTION: Venous thromboembolism (VTE) is a serious, frequent, and preventable medical complication in hospitalized patients. Although the efficacy of prophylaxis (pharmacological and/or mechanical) has been demonstrated, compliance with prophylaxis is poor at international and national levels. AIM: To determine the indication and use of pharmacological thromboprophylaxis in hospitalized patients in Uruguay. METHODS: An observational, descriptive, cross-sectional, multicentre study involving 31 nationwide healthcare facilities was conducted. Baseline characteristics associated with hospital admission, the percentage of the population with an indication for thromboprophylaxis, and the percentage of patients receiving pharmacological thromboprophylaxis were assessed. The VTE risk was determined using the Padua score for medical patients; the Caprini score for surgical patients; the Royal College of Obstetricians and Gynaecologists (RCOG) guidelines for pregnant-postpartum patients. RESULTS: 1925 patients were included, representing 26% of hospitalized patients in Uruguay. 71.9% of all patients were at risk of VTE. Of all patients at risk of VTE, 58.6% received pharmacological thromboprophylaxis. The reasons for not receiving thromboprophylaxis were prescribing omissions in 16.1% of cases, contraindication in 15.9% and 9.4% of patients were already anticoagulated for other reasons. Overall, just 68% of patients were "protected" against VTE. Recommendations of major thromboprophylaxis guidelines were followed in 70.1% of patients at risk. CONCLUSIONS: Despite the progress made in adherence to thromboprophylaxis indications, nonadherence remains a problem, affecting one in six patients at risk of VTE in Uruguay.

[Comparison between CHOP-like and R-CHOP in diffuse large B cell and follicular lymphoma]. / Comparación entre CHOP-like y R-CHOP en pacientes con linfoma no Hodgkin difuso de grandes células B y folicular: 10 años de experiencia del Hospital de Clínicas de Montevideo, Uruguay.

BACKGROUND: The most common types of non-Hodgkin lymphoma (NHL) are diffuse large B cell (DLBCL) and follicular (FL). AIM: To analyze the benefit of Rituxi-mab in overall survival (OS) of patients with NHL. MATERIAL AND METHODS: Review of medical record of 230 adult patients with a first episode of NHL admitted between 2002 and 2011. We included 67 patients with DLBCL and 36 patients with FL. RESULTS: The overall response (OR) was 64% with 39% complete remissions (CR) in DLBCL treated with CHOP-like and 100% with 89% CR with R-CHOP. The median OS with CHOP-like was 21 months versus not attained R-CHOP (p = 0.016). There was a statistically significant difference in median event-free survival (EvFS) in favor of R-CHOP: not attained versus 8.3 months for CHOP-like (log rank (p = 0.002)). In FL, the OR in patients treated with R-CHOP or R-CHOP-like was 85%) with 54% CR. With CHOP-like the OR was 59%> with 18% CR. The OS at 24 and 36 months in patients treated with R-CHOP or R-CHOP-like was 83 and 65%. The figures for patients treated with CHOP-like were 80 and 66%> respectively. The progression free survival (PFS) was 21 months with CHOP-like versus not attained with R-QT (p = 0,043). CONCLUSIONS: When Rituximab was added to CHOP, there was a higher CR, EvFS and OS in DLBCL and higher CR and PFS in FL.

[Cytarabine and skin reactions in acute myeloid leukemia]. / Citarabina y reacciones cutáneas en leucemia aguda mieloide.

Cytarabine is an antimetabolite used in the treatment of acute myeloid leukemia (AML). It has many adverse effects as: myelosuppression, toxic reactions involving central nervous system, liver, gastrointestinal tract, eyes or skin. Dermatologic toxicity is often described as rare; nevertheless there are differences in the reported frequency. We performed a retrospective study including all AML treated with chemotherapy that involved cytarabine between 1st July of 2006 and 1st July of 2012; 46 patients were included with a median age of 55 years. The overall incidence of skin reactions was 39% (n = 18). Sex, age, history of atopy, history of drug reactions, or dose of cytarabine used, were not associated with them. Skin reactions were observed from 2 to 8 days after treatment started. Considering injury degree: 27.8% had grade 1, 38.9% grade 2 and 33.3% grade 3. We did not find any injury grade 4 or death associated with skin toxicity. As for the type of injury: 55.6% presented macules, 22.2% papules and 22.2% erythema. Lesions distribution was diffuse in 52% of patients, acral in 39.3%, and at flexural level in 8.7%. Adverse cutaneous reactions secondary to the administration of cytarabine are frequent in our service and include some cases with severe involvement. Although these reactions usually resolve spontaneously, they determine an increased risk of infection and a compromise of the patient quality of life.

Hemoglobin Denver, a cause of desaturated pulse oximetry. A pediatric case report. / Hemoglobina Denver, una causa de desaturación en oximetría de pulso. Reporte de caso en un paciente pediátrico.

Hemoglobinopathies are genetic disorders that affect the hemoglobin (Hb) molecule. Mutations in the alpha or beta chains altering the Hb tetramer may modify the molecule's oxygen-binding capacity. Hemoglobinopathies with low oxygen affinity may occur with cyanosis and an altered pulse oximetry reading, leading to unnecessary and sometimes invasive tests to rule out cardiovascular and respiratory conditions. In the case report described here, we present an asymptomatic pediatric patient who consulted for desaturated pulse oximetry. Her initial laboratory tests showed normocytic, normochromic anemia. Venous blood gas samples showed an elevated p50. After using extensive diagnostic tools, a variant of Hb with low oxygen affinity was diagnosed: Hb Denver.

Las hemoglobinopatías son trastornos genéticos que afectan a la molécula de hemoglobina (Hb). Las mutaciones en las cadenas a o b que alteran el tetrámero de Hb pueden modificar la capacidad de la molécula para unirse al oxígeno. Las hemoglobinopatías con baja afinidad al oxígeno pueden presentarse con cianosis y una lectura alterada de la oximetría de pulso, lo que lleva a pruebas innecesarias y, a veces, invasivas para descartar afecciones cardiovasculares y respiratorias. En el siguiente reporte de caso, presentamos a una paciente pediátrica, asintomática, que se presentó a la consulta por detección de desaturación en oximetría de pulso. Las pruebas de laboratorio iniciales mostraron una anemia normocítica, normocrómica. Las muestras de gas venoso demostraron una p50 elevada. Después de extensas herramientas de diagnóstico, se diagnosticó una variante de Hb con baja afinidad al oxígeno, Hb Denver.

Increasing access to hematopoietic cell transplantation in Latin America: results of the 2018 LABMT activity survey and trends since 2012.

A total of 5642 hematopoietic cell transplants (HCT) in 5445 patients (2196-40% allogeneic and 3249-60% autologous) were reported by 127 teams in 14 Latin American countries that answered the 2018 LABMT/WBMT Global Transplant Activity survey. The transplant rate (defined as the number of first transplants per 10 million inhabitants per year) was 85 (51 autologous and 34 allogeneic) in 2018. The main indications for allogeneic HCT were acute leukemias (60%), while plasma cell disorders and lymphomas were the most common conditions warranting autologous HCT (50 and 36%, respectively). In the allogeneic HCT, HLA-identical siblings were the main type of donor (44%) followed by related mismatched/haploidentical donors (32%). Peripheral blood stem cells were used in 98% of the autologous and in 64% of the allogeneic transplants. From 2012 to 2018, there was a 64% increase of reported HCT (54% in autologous and 80% in allogeneic). In the allogeneic setting, the most pronounced increase in donor type was observed in haploidentical relatives (from 94 procedures in 2012 up to 710 in 2018), surpassing unrelated donors as of 2017. Significant trends detected in Latin America include rising numbers of the procedures reported, a faster increase in allogeneic HCT compared with autologous HCT and a significant increase in family mismatched/haploidentical donors. The LABMT/WBMT activity survey provides useful data to understand the HCT activity and trends in Latin America.

5-Azacytidine restores interleukin 6-increased production in mesenchymal stromal cells from myelodysplastic patients.

INTRODUCTION: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematological diseases. In addition to defects in hematologic progenitor and stem cells, dysfunctions in the bone marrow microenvironment (BMM) participate in the MDS pathogenesis. Furthermore, the immune response is deregulated by the pro-inflammatory response prevailing in low-risk MDS, while immunosuppression predominates in high-risk MDS. Mesenchymal stromal cells (MSC), part of the BMM, are characterized by plastic adherent growth and multipotentiality. They exhibit immunomodulatory properties and sustain hematopoiesis. There is conflicting evidence regarding their status in MDS. The aim of this study was to characterize MDS-MSC and evaluate the effect of 5-Azacytidine. METHODS: The MSC from MDS patients and controls were cultured and characterized according to the International Society of Cell Therapy recommendations. Immunomodulatory properties were assessed by studying the MSD cytokine production, using the cytometric bead array. We evaluated the effect of 5-Azacytidine on the MSC cytokine production. RESULTS: We included 35 MDS patients and 22 controls. The MSC from patients and controls were cultured and characterized. The MSC from patients showed morphological differences, but there were no differences in immunophenotype or multipotentiality. The interleukin 6 (IL-6) was the main MSC secreted cytokine. The MDS-MSC produced higher levels of IL-6, IL-17, interferon gamma, or interferon γ (INF-γ), and tumor necrosis factor alpha (TNF-α). The in vitro 5-Azacytidine treatment induced a significant decrease in the IL-6 production by MDS-MSC. CONCLUSIONS: The MDS-MSC show an increased production of pro-inflammatory cytokines. The in vitro treatment with 5-Azacytidine lead to a significant reduction in the IL-6 production by the MDS-MSC, restoring the IL-6 levels to those found in controls. The MSC produced inflammatory cytokines involved in the MDS pathogenesis, representing a potential future therapeutic target. Moreover, 5-Azacytidine may have a stromal effect, modulating the immune response in MDS.

Hb S-San Martin: a new sickling hemoglobin with two amino acid substitutions [ß6(A3)Glu→Val;ß105(G7)Leu→Pro] in an Argentinean family.

A new sickling hemoglobin (Hb) detected in an Argentinean family from San Martín, Buenos Aires, Argentina, is hereby described. Two mutations were identified on the same ß-globin gene resulting in a new variant named Hb San Martin. One mutation was found on exon 1, corresponding to Hb S [ß6Glu→Val, GAG>GTG] and the second one on exon 3 at ß105(G7)Leu→Pro, CTC>CCC. The replacement of leucine by proline will likely impair the structure breaking helix G and causing instability of the molecule and the clinical manifestations typical of unstable Hbs. The mutation at ß105 seemed to be a de novo one in our patients, arising on a previously mutated gene, due to the fact that Hb S is the most frequent structural variant.

Phenotypic and genotypic characterization of glucose-6-phosphate dehydrogenase deficiency in Argentina. Retrospective and descriptive study. / Caracterización fenotípica y genotipica de la deficiencia de glucosa-6-fosfato deshidrogenasa en Argentina. Estudio retrospectivo y descriptivo.

Glucose-6-phosphate dehydrogenase deficiency is an erythrocyte enzyme disorder caused by mutations in the G6PD gene, which has an X-linked inheritance. Here we analyze the clinical and laboratory characteristics of 24 subjects with G6PD deficiency over 25 years. Their median age at diagnosis was 10.2 years (range: 0.6-56.4). No symptoms were observed in 54.2 % of patients, whereas 25 % had chronic non-spherocytic hemolytic anemia; 12.5 %, neonatal jaundice and postinfectious hemolytic anemia; and 8.3 %, acute hemolytic anemia after ingestion of fava beans. The 24 studied patients had variants that had been previously described in the bibliography. The clinical characteristics observed here were consistent with the variants found. A total of 21 women from the maternal line of affected subjects were identified as deficiency carriers using molecular biology techniques, so they received the corresponding genetic counseling.

La deficiencia de glucosa-6-fosfato deshidrogenasa es la enzimopatía eritrocitaria causada por mutaciones en el gen G6PD, cuya herencia está ligada al cromosoma X. Se analizan las características clínicas y de laboratorio de 24 individuos con deficiencia de G6PD durante 25 años. La edad mediana al momento del diagnóstico fue 10,2 años (rango: 0,6-56,4). El 54,2 % de los pacientes fueron asintomáticos, mientras que el 25 % presentó anemia hemolítica crónica no esferocítica; el 12,5 %, ictericia neonatal y anemia hemolítica posinfecciones, y el 8,3 %, anemia hemolítica aguda pos ingesta de habas. Los 24 pacientes estudiados presentaron variantes descritas previamente en la literatura. Las características clínicas observadas estuvieron acordes con las variantes encontradas. Veintiuna mujeres, pertenecientes a la rama materna de los individuos afectados, pudieron ser identificadas por biología molecular como portadoras de la deficiencia, por lo que recibieron el consejo genético correspondiente.

Trastornos adquiridos y congénitos de la deficiencia de vitamina B12 en niños / Acquired and inherited disorders of vitamin B12 deficiency in children

Vitamin B12 is an essential micronutrient for cell growth and the development of the central nervous system. Its deficiency can manifest clinically as megaloblastic anemia, peripheral neuropathy, myelopathy and neuropsychiatric disorders. Early detection and treatment are essential as it can cause irreversible neurological sequelae. Diagnosis is often challenging as it is based on clinical and biochemical features. Clinically, the symptoms are nonspecific and equivocal. Biochemically, there is no gold standard to detect Cobalamin deficiency. The available biomarkers do not have a defined cut-off value or are not sensitive or specific enough. This article exposes the different causes of vitamin B12 deficiency, analyzes the advantages and disadvantages of biochemical markers and, for the first time, proposes an algorithmic diagnosis using biomarkers and therapeutic tests. The ultimate goal is to alert pediatricians to the difficulties of diagnosing vitamin B12 deficiency and strategies are proposed to differentiate between acquired and congenital cobalamin conditions. Finally, the treatment according to the etiology is described in a practical manner, as well as the expected time for improvement of the biochemical parameters.

La vitamina B12 es un micronutriente fundamental para el crecimiento celular y el desarrollo del sistema nervioso central. Su deficiencia puede manifestarse clínicamente como anemia megaloblástica, neuropatía periférica, mielopatía y trastornos neuropsiquiátricos. La detección y el tratamiento tempranos son esenciales, ya que esta deficiencia puede generar secuelas neurológicas irreversibles. El diagnóstico suele ser un desafío, ya que se basa en pilares clínicos y bioquímicos. Clínicamente, los síntomas son inespecíficos y equívocos. Bioquímicamente no existe un gold standard para diagnosticar la deficiencia de cobalamina. Los biomarcadores existentes no presentan un valor de corte definido o no son lo suficientemente sensibles o específicos. Este trabajo expone las diferentes causas de deficiencia de vitamina B12, analiza las ventajas y desventajas de los marcadores bioquímicos y por primera vez se plantea un algoritmo diagnóstico mediante biomarcadores y pruebas terapéuticas. El objetivo último es alertar a los pediatras acerca las dificultades que representa el diagnóstico de deficiencia de vitamina B12 y se proponen estrategias para diferenciar cuadros adquiridos versus congénitos de la deficiencia de cobalamina. Por último, se describe de manera práctica el tratamiento según la etiología así como el tiempo esperado para la mejoría de los parámetros bioquímicos.

Digital Ischemia as an Unusual Manifestation of Hodgkin's Lymphoma.

Digital ischemia is associated with atherosclerotic, thromboembolic, or connective tissue diseases. Less often, it can be related to malignancy. Paraneoplastic vascular acrosyndromes (Raynaud's syndrome, acrocianosis, and acronecrosis) are associated with adenocarcinoma and less frequently with hematological malignancies. We report the case of a 45-year-old male, smoker, with a 10-day history of pain, cyanosis, and progressive digital necrosis in both hands. In the previous four months, he noticed painless mass in the right axillary gap, drenching night sweats, and weight loss. Physical examination at admission highlighted necrotic lesions on the distal phalanges of both hands (except the thumbs), enlarged lymph nodes in right axillary, and right supraclavicular gaps. Arteriography of upper limbs demonstrated a distal stop in all bilateral digital arteries. Digital ischemia was interpreted as a paraneoplastic phenomenon after other common etiologies were ruled out. Amputation of three phalanges was required due to necrosis. Biopsy of axillary nodes demonstrated nodular sclerosis classical Hodgkin's lymphoma (HL). The patient started conventional ABVD protocol (doxorubicin, bleomycin, vinblastine, and dacarbazine). After 6 cycles, he remained asymptomatic and symptoms of digital ischemia were completely resolved. It was concluded that the presence of acral vascular syndromes should alert the physician about the possibility of underlying malignant disease. Prompt investigation and treatment should be rapidly performed to avoid digital sequelae.

[Magnetic resonance as initial screening diagnosis of secondary involvement of central nervous system in NHL diffuse large B cell lymphoma] / Resonancia magnética como screening inicial de diagnóstico de compromiso secundario del sistema nervioso central en LNH difuso de grandes Células B.

Background: Background: Central Nervous System (CNS) relapse in Diffuse Large B-cell Lymphoma occurs mostly 6-8 months after disease onset. This has led to propose that CNS infiltration is an early event in the evolution of the disease. We intend to evaluate the role of magnetic resonance imaging (MR) at diagnosis to detect early SNC compromise. Methods: Prospective longitudinal cohort's study in DGCB patients treated at Hospital de Clínicas between 2013 and 2015. Skull MRI was performed in all patients at diagnosis and lumbar puncture was done according to predefined risk factors. Results: 35 patients were analyzed. Median age: 68 years (24-85 years). Stage III-IV: 62%, 57% good prognosis according to RIPI score and 43% poor prognosis. MRI was performed in all patients, with no pathological findings in any of them. Twenty-one patients fullfilled criteria for cerebrospinal fluid study. Twenty-two patients were studied and received intrathecal methotrexate prophylaxis. Meningeal relapse was observed in a single patient who had negative studies at diagnosis and had received complete prophylaxis at the end of the 6 R-CHOP series. Conclusions: Only one of the 35 patients relapsed in the CNS. This patient had a noral MRI and CSF study at diagnosis and had received prophylaxis with intrathecal chemotherapy. This results lead us to believe that the value of MRI to detect early infiltration in asymptomatic patients at diagnosis is low.

Antecedentes: la recaída en el Sistema Nervioso Central (SNC) del Linfoma No Hodgkin Difuso de Grandes Células B ocurre más frecuentemente 6-8 meses del debut de la enfermedad. Esto ha levado a plantear que la infiltración en SNC es un evento temprano en esta enfermedad. Nos proponemos evaluar el valor de la realización de estudio imagenológico por Resonancia Magnética (RM) al debut para detectar compromiso precoz. Materiales y métodos: Estudio longitudinal prospectivo de cohortes en LNH DGCB tratados en el Hospital de Clínicas entre 2013 y 2015. A todos los pacientes se les realizó RM de cráneo al debut y estudio de líquido cefaloraquídeo (LCR) según factores de riesgo predefinidos. Resultados: Se analizaron 35 pacientes. Mediana de edad: 68 años (24-85 años). Estadío III-IV: 62%; 57% presentaron buen pronóstico según score RIPI al debut y 43% mal pronóstico. Se realizó RM a todos los pacientes, no habiéndose encontrado hallazgos patológicos en ninguno de ellos. Veintitres pacientes tuvieron criterio de estudio del LCR de los cuales veintidós se estudiaron y recibieron profilaxis con metotrexate intratecal. Se observó recaída meníngea en una única paciente con estudios negativos al debut y profilaxis completa al mes de finalizadas las 6 series de R-CHOP. Conclusiones: De 35 pacientes uno sólo recayó en el SNC; el mismo había recibido profilaxis con quimioterapia intratecal y presentó una RM normal al debut de su enfermedad. Los resultados nos conducen a pensar que el valor de la RM para detectar precozmente infiltración en pacientes asintomáticos al debut es bajo.

Development validation and evaluation of the knowledge test on cardiopulmonary resuscitation and correct use of the automated external defibrillator in Asunción 2023

Introduction: in out-of-hospital cardiac arrest, early and efficient intervention through cardiopulmonary resuscitation (CPR) maneuvers and the use of the automated external defibrillator (AED) are the cornerstone for survival. Instruments that improve education would increase the responsiveness of lay personnel. Objectives: to develop, validate and evaluate a knowledge test on cardiopulmonary resuscitation and correct use of the automated external defibrillator in Asunción during 2023. Methodology: observational cross-sectional study, non-probabilistic sample for convenience of lay personnel users of mass attendance centers in Asunción. An exclusive questionnaire was developed on knowledge in cardiopulmonary resuscitation and the use of the automated external defibrillator (KOR-AED) based on the chain of survival in out-of-hospital cardiac arrest. Content, construct, and internal consistency were validated using expert opinion, factor analysis and Cronbach's alpha. Results: a total of 200 lay people participated, mostly shopping mall customers, with a predominance of men (63.5 %) (127), between 25-29 years old 28.5% (57). 61.5 % (123) had a university education, 75.5 % (151) had not related to health, 52 % (104) had prior knowledge of CPR, but 81.5 % (163) did not. The test showed reliability and suitability for factor analysis (Cronbach's alpha 0.75, Kaiser-Meyers-Olkin; 0.78, Bartlett p<0.05). The questions covered the first three links in the chain of survival, with items of medium to high difficulty. Women performed significantly better (p=0.04). Conclusion: the KOR-AED test is a valid and reliable instrument to improve the education of the layperson in CPR and use of the AED based on the chain of survival.

Introducción: en la parada cardíaca extrahospitalaria la actuación precoz y eficiente mediante maniobras de reanimación cardiopulmonar (RCP) y uso del desfibrilador externo automático (DEA) constituyen la piedra angular para la supervivencia. Instrumentos que mejoren la educación aumentarían la respuesta del personal lego. Objetivos: desarrollar, validar y evaluar una prueba de conocimientos sobre reanimación cardiopulmonar y uso correcto del desfibrilador externo automático en Asunción durante el 2023. Metodología: estudio observacional corte transversal, muestro no probabilístico por conveniencia de personal lego usuarios de centros de concurrencia masiva de Asunción. Se desarrolló un cuestionario exclusivo sobre conocimientos en reanimación cardiopulmonar y uso del desfibrilador externo automático (COR-DEA) basado en la cadena de supervivencia en parada cardíaca extrahospitalaria. Se validó el contenido, el constructo y la consistencia interna mediante la opinión de experto, análisis de factores y el alfa de Cronbach. Resultados: participaron 200 legos mayormente clientes de shoppings, predominando hombres 63,5 % (127) entre 25-29 años 28,5 % (57). Con educación universitaria 61,5 % (123), no relacionados con la salud 75,5 % (151), con conocimientos previos en RCP 52 % (104), pero no en DEA 81,5 % (163). El test mostró fiabilidad y adecuación para análisis factorial (Alfa de Cronbach 0.75, Kaiser-Meyers-Olkin; 0.78, Bartlett p<0.05). Las preguntas abarcarón los tres primeros eslabones de la cadena de supervivencia, con ítems de dificultad media a alta. Las mujeres tuvieron significativamente mejor desempeñó (p=0.04). Conclusión: la prueba COR-DEA es un instrumento válido y fiable para mejorar la educación del lego en RCP y uso del DEA basado en la cadena de supervivencia.

Hemoglobina Denver, una causa de desaturación en oximetría de pulso. Reporte de caso en un paciente pediátrico / Hemoglobin Denver, a cause of desaturated pulse oximetry. A pediatric case report

Las hemoglobinopatías son trastornos genéticos que afectan a la molécula de hemoglobina (Hb). Las mutaciones en las cadenas a o b que alteran el tetrámero de Hb pueden modificar la capacidad de la molécula para unirse al oxígeno. Las hemoglobinopatías con baja afinidad al oxígeno pueden presentarse con cianosis y una lectura alterada de la oximetría de pulso, lo que lleva a pruebas innecesarias y, a veces, invasivas para descartar afecciones cardiovasculares y respiratorias. En el siguiente reporte de caso, presentamos a una paciente pediátrica, asintomática, que se presentó a la consulta por detección de desaturación en oximetría de pulso. Las pruebas de laboratorio iniciales mostraron una anemia normocítica, normocrómica. Las muestras de gas venoso demostraron una p50 elevada. Después de extensas herramientas de diagnóstico, se diagnosticó una variante de Hb con baja afinidad al oxígeno, Hb Denver.

Hemoglobinopathies are genetic disorders that affect the hemoglobin (Hb) molecule. Mutations in the alpha or beta chains altering the Hb tetramer may modify the molecule's oxygen-binding capacity. Hemoglobinopathies with low oxygen affinity may occur with cyanosis and an altered pulse oximetry reading, leading to unnecessary and sometimes invasive tests to rule out cardiovascular and respiratory conditions. In the case report described here, we present an asymptomatic pediatric patient who consulted for desaturated pulse oximetry. Her initial laboratory tests showed normocytic, normochromic anemia. Venous blood gas samples showed an elevated p50. After using extensive diagnostic tools, a variant of Hb with low oxygen affinity was diagnosed: Hb Denver.