Macrophage-derived IL-18 and increased fibrinogen deposition are age-related inflammatory signatures of vascular remodeling.

Aging has been associated with pathological vascular remodeling and increased neointimal hyperplasia. The understanding of how aging exacerbates this process is fundamental to prevent cardiovascular complications in the elderly. This study proposes a mechanism by which aging sustains leukocyte adhesion, vascular inflammation, and increased neointimal thickness after injury. The effect of aging on vascular remodeling was assessed in the rat balloon injury model using microarray analysis, immunohistochemistry, and LINCOplex assays. The injured arteries in aging rats developed thicker neointimas than those in younger animals, and this significantly correlated with a higher number of tissue macrophages and increased vascular IL-18. Indeed, IL-18 was 23-fold more abundant in the injured vasculature of aged animals compared with young rats, while circulating levels were similar in both groups of animals. The depletion of macrophages in aged rats with clodronate liposomes ameliorated vascular accumulation of IL-18 and significantly decreased neointimal formation. IL-18 was found to inhibit apoptosis of vascular smooth muscle cells (VSMC) and macrophages, thus favoring both the formation and inflammation of the neointima. In addition, injured arteries of aged rats accumulated 18-fold more fibrinogen-γ than those of young animals. Incubation of rat peritoneal macrophages with immobilized IL-18 increased leukocyte adhesion to fibrinogen and suggested a proinflammatory positive feedback loop among macrophages, VSMC, and the deposition of fibrinogen during neointimal hyperplasia. In conclusion, our data reveal that concentration changes in vascular cytokine and fibrinogen following injury in aging rats contribute to local inflammation and postinjury neointima formation.

Hybrid operating room with ceiling mounted imaging system assisted pre-operative and intra-operative lung nodule localization for thoracoscopic resections: a 5-year case series.

BACKGROUND: Video-assisted thoracoscopic (VATS) lung resections are increasingly popular and localization techniques are necessary to aid resection. We describe our experience with hybrid operating room (OR) cone-beam computed tomography (CT) assisted pre-operative and intra-operative lesion localization of lung nodules for VATS wedge resections, including our novel workflow using the hybrid OR cone-beam CT to re-evaluate patients who have undergone pre-operative localization for those who are unsuitable for intra-operative localization. METHODS: Retrospective analysis of all consecutive patients with small (≤ 20 mm), deep (≥ 10 mm distance from pleura) and/or predominantly ground-glass nodules selected for lesion localization in the Interventional Radiology suite followed by re-evaluation with cone-beam CT in the hybrid OR (pre-operative), or in the hybrid OR alone (intra-operative), prior to intentional VATS wedge performed by a single surgeon at our centre from January 2017 to December 2021. RESULTS: 30 patients with 36 nodules underwent localization. All nodules were successfully resected with a VATS wedge resection, although 10% of localizations had hookwire or coil dislodgement. The median effective radiation dose in the pre-operative group was 10.4 mSV including a median additional radiation exposure of 0.9 mSV in the hybrid OR for reconfirmation of hookwire or coil position prior to surgery (p = 0.87). The median effective radiation dose in the intra-operative group was 3.2 mSV with a higher mean rank than the intra-operative group, suggesting a higher radiation dose (p = 0.01). CONCLUSIONS: We demonstrate that our multidisciplinary approach utilizing the hybrid OR is safe and effective. Intra-operative localization is associated with lower radiation doses. Routine use of cone-beam CT to confirm the position of the physical marker prior to surgery in the hybrid OR helps mitigate consequences of localization failure with only a modest increase in radiation exposure.

Relapsing COVID-19 infection as a manifestation of Good syndrome: a case report and literature review.

Good syndrome (GS) is a rare acquired immunodeficiency disease characterized by the presence of thymoma with combined B and T cell immunodeficiency in adults. Recurrent bacterial infections, particularly sinopulmonary infections caused by encapsulated bacteria, remain the most common infective presentation of GS; however, relapsing viral infections have also been reported, likely due to impaired T cell-mediated immunity. Relapsing COVID-19 infection, however, has not been previously reported as a manifestation of GS. We present two cases of relapsing COVID-19 infection in patients with GS; in one case, relapsing COVID-19 was the first manifestation of newly diagnosed GS.

Enhancing Part-to-Part Repeatability of Force-Sensing Resistors Using a Lean Six Sigma Approach.

Polymer nanocomposites have found wide acceptance in research applications as pressure sensors under the designation of force-sensing resistors (FSRs). However, given the random dispersion of conductive nanoparticles in the polymer matrix, the sensitivity of FSRs notably differs from one specimen to another; this condition has precluded the use of FSRs in industrial applications that require large part-to-part repeatability. Six Sigma methodology provides a standard framework to reduce the process variability regarding a critical variable. The Six Sigma core is the DMAIC cycle (Define, Measure, Analyze, Improve, and Control). In this study, we have deployed the DMAIC cycle to reduce the process variability of sensor sensitivity, where sensitivity was defined by the rate of change in the output voltage in response to the applied force. It was found that sensor sensitivity could be trimmed by changing their input (driving) voltage. The whole process comprised: characterization of FSR sensitivity, followed by physical modeling that let us identify the underlying physics of FSR variability, and ultimately, a mechanism to reduce it; this process let us enhance the sensors' part-to-part repeatability from an industrial standpoint. Two mechanisms were explored to reduce the variability in FSR sensitivity. (i) It was found that the output voltage at null force can be used to discard noncompliant sensors that exhibit either too high or too low sensitivity; this observation is a novel contribution from this research. (ii) An alternative method was also proposed and validated that let us trim the sensitivity of FSRs by means of changing the input voltage. This study was carried out from 64 specimens of Interlink FSR402 sensors.

Real-World Evidence of Epidemiology and Clinical Outcomes in Multiple Myeloma, Findings from the Registry of Hemato-Oncologic Malignancies in Colombia, Observational Study.

INTRODUCTION/BACKGROUND: Multiple Myeloma (MM) is a plasma cell derived clonal disorder that represents around 1% of all newly diagnosed neoplasms. Limited data regarding MM treatment in Latin America is available, and access to novel agents for a substantial portion of the population is limited by their high costs. MATERIALS (OR PATIENTS) AND METHODS: RENEHOC is a bidirectional (retrospective and prospective) multicenter observational registry of hematological malignancies in Colombia. MM patients included up to July 2020 were analyzed on this report. RESULTS: 890 are reported with a median follow-up of 18 months (IQR: 7-42 months). Patients were classified by age group (≤ or > 65 years). Median age at diagnosis was 67 years (IQR: 59-75 years) and 47.1% of patients were women. 709 patients (79.6%) received Bortezomib-based schemes as part of the first line. Two hundred and fifty-two patients (28.3%) were consolidated with Autologous Stem Cell Transplantation (ASCT) in first-line. ASCT consolidation and age were the main independent factors influencing outcomes; in the non-ASCT cohort, 5-year overall survival was 48.7% (CI 41.8-55.2) compared to 80.7% (CI 73-86.4) in ASCT patients. CONCLUSION: This data depicts the reality of MM in Colombia, which likely reflects other Latin American countries, where access barriers to diagnosis and treatment are echoed in advanced stage diagnosis and a low rate of transplants. These seem to negatively impact survival despite the availability of most novel drugs approved for this disease. Thus, emphasizing the paradox that prevails in most of the region: availability without equitable access.

Detection of viable SARS-CoV-2 in deep respiratory specimens despite negative nasopharyngeal SARS-CoV-2 RT-PCR: Occult COVID-19 as an unsuspected cause of pulmonary infiltrates in immunocompromised patients.

Background: Prolonged shedding/relapse of COVID-19 infection has been reported, particularly in patients who received anti-CD20 agents (eg. rituximab). However, cases of occult COVID-19, in which SARS-CoV-2 persistence in lung parenchyma is diagnosed despite clearance from nasopharyngeal (NP) specimens, are uncommon. Case summary: We describe two cases of occult COVID-19 in immunocompromised patients. Both patients had received rituximab previously. Both cases initially presented as ground-glass infiltrates on lung imaging; the diagnosis was originally not suspected due to repeated demonstration of negative SARS-CoV-2 from NP specimens, and alternative etiologies were originally considered. Persistence of SARS-CoV-2 in lung parenchyma, however, was demonstrated on bronchoalveolar lavage (BAL) specimens; additionally, isolation of viable SARS-CoV-2 virus and detection of SARS-CoV-2 nucleocapsid and spike-protein antigen in lung tissue on immunohistochemistry close to 3-months from primary infection strongly suggested ongoing viral persistence and replication as a driver of the lung parenchymal changes, which resolved after antiviral treatment. Discussion: Occult COVID-19 can be a cause of unexplained ground-glass infiltrates on lung imaging; negative NP samples do not rule out SARS-CoV-2 persistence and invasive sampling must be considered. The unsuspected presence of viable virus on BAL, however, highlights that procedurists perfoming aerosol-generating-procedures during an ongoing pandemic wave must also practise appropriate infection-prevention precautions to limit potential exposure.

Improving Recruitment for a Newborn Screening Pilot Study with Adaptations in Response to the COVID-19 Pandemic.

Seven months after the launch of a pilot study to screen newborns for Duchenne Muscular Dystrophy (DMD) in New York State, New York City became an epicenter of the coronavirus disease 2019 (COVID-19) pandemic. All in-person research activities were suspended at the study enrollment institutions of Northwell Health and NewYork-Presbyterian Hospitals, and study recruitment was transitioned to 100% remote. Pre-pandemic, all recruitment was in-person with research staff visiting the postpartum patients 1-2 days after delivery to obtain consent. With the onset of pandemic, the multilingual research staff shifted to calling new mothers while they were in the hospital or shortly after discharge, and consent was collected via emailed e-consent links. With return of study staff to the hospitals, a hybrid approach was implemented with in-person recruitment for babies delivered during the weekdays and remote recruitment for babies delivered on weekends and holidays, a cohort not recruited pre-pandemic. There was a drop in the proportion of eligible babies enrolled with the transition to fully remote recruitment from 64% to 38%. In addition, the proportion of babies enrolled after being approached dropped from 91% to 55%. With hybrid recruitment, the proportion of eligible babies enrolled (70%) and approached babies enrolled (84%) returned to pre-pandemic levels. Our experience adapting our study during the COVID-19 pandemic led us to develop new recruitment strategies that we continue to utilize. The lessons learned from this pilot study can serve to help other research studies adapt novel and effective recruitment methods.

Idiopathic recurrent serositis-Off the beaten track.

A 63-year-old female presented with chest pain and fever, and was found to have recurrent pleuropericardial effusions. Extensive investigations including infection screen and serologies, autoimmune screen and pleural and pericardial biopsy revealed no secondary aetiologies. She was diagnosed with idiopathic recurrent serositis (IRS). Our patient developed rash to naproxen, so she was started on colchicine monotherapy and responded well clinically. A review of the literature demonstrated that pleuropericardial effusions are rare occurrences, with patients occasionally being perceived as a medical enigma. This case study recommends an approach to guide physicians in their diagnosis and management of patients with pleuropericardial syndrome. Our case had an inflammatory phenotype, either autoimmune or seronegative serositis of unclear aetiology, which was recurrent and required pharmacological treatment. While the treatment for IRS lies in combined therapy with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and colchicine, monotherapy with colchicine was effective in the treatment and preventing recurrence in our unique case.

B careful: Humoral responses and COVID-19 severity.

Neutralizing antibody responses to SARS-CoV-2, though often of limited longevity, have generally been assumed to be protective against COVID-19 disease.

Reactivation of Chagas disease after autologous hematopoietic stem cell transplantation.

Chagas disease (CD) is a protozoan zoonosis caused by Trypanosoma cruzi. Reactivation of CD occurs via drug-induced immunosuppression before and during transplantation. Here, we report the case of a 62-year-old man diagnosed with classic Hodgkin lymphoma who received highly aggressive conditioning chemotherapy before undergoing stem cell transplantation (SCT). The patient tested positive for CD in pre-transplantation evaluation. The patient exhibited persistent fever and elevated C-reactive protein levels before and after SCT, and was treated with antibiotics. Micro-Strout test showed evidence of trypomastigotes and he was treated with benznidazole until tested negative. Post-transplantation seropositive patients should be screened for possible reactivation.

Cardiovascular Disease in Latin American Women Gaps and opportunities

Abstract Cardiovascular disease (CVD) remains the leading cause of death in women. This review will address the known disparities in cardiovascular care concerning diagnosing and treating of heart disease in Latin American (LA) women. Gender-specific differences regarding the incidence, treatment, and outcomes of common cardiovascular pathology are increasingly recognized. Today, we identify that women have cardiovascular risk factors (CRFs), specifying the traditional, emerging, unique, or sex-specific determinants and the social and biological determinants that play a leading role in the prevention of CVD. The purpose of this article is to review the literature on cardiovascular disease in LA women, focusing on ischemic heart disease (IHD), valve disease (VD), heart failure, and cardiac rehabilitation (CR), where disparities continue to affect outcomes. Understanding the unique cardiovascular risk profile and barriers to optimal treatment outcomes in women is imperative to eliminate the current disparities in CVD.

Autologous hematopoietic stem cell transplantation in a patient with refractory seropositive myasthenia gravis: A case report.

Myasthenia gravis is a neuromuscular autoimmune disease characterized by fatigable weakness of skeletal muscles that results from an antibody-mediated immunological attack directed at acetylcholine postsynaptic receptors. Autologous hematopoietic stem cell transplantation is considered as a treatment option in refractory cases of myasthenia gravis. A 56-year-old Colombian male presented with six months of progressive hoarseness and dysphagia, with a positive repetitive stimulation test suggestive of end plate neuromuscular disease. Myasthenia gravis was confirmed with serology testing that reported presence of circulating acetylcholine postsynaptic receptors antibodies. The patient received several lines of pharmacological treatment and thymectomy without control of symptoms, requiring admission to the intensive care unit and mechanical ventilation in two occasions. Patient underwent autologous hematopoietic stem cell transplantation and has been in complete clinical remission for 65 months. Hematopoietic stem cell transplantation is a well-tolerated treatment that should be considered over conventional therapy in selected patients with refractory myasthenia gravis.

Reactivation of Chagas disease after autologous hematopoietic stem cell transplantation

Abstract Chagas disease (CD) is a protozoan zoonosis caused by Trypanosoma cruzi. Reactivation of CD occurs via drug-induced immunosuppression before and during transplantation. Here, we report the case of a 62-year-old man diagnosed with classic Hodgkin lymphoma who received highly aggressive conditioning chemotherapy before undergoing stem cell transplantation (SCT). The patient tested positive for CD in pre-transplantation evaluation. The patient exhibited persistent fever and elevated C-reactive protein levels before and after SCT, and was treated with antibiotics. Micro-Strout test showed evidence of trypomastigotes and he was treated with benznidazole until tested negative. Post-transplantation seropositive patients should be screened for possible reactivation.

Lesión miocárdica en una paciente con lupus eritematoso sistémico: Un reto diagnóstico / Myocardial lesion in a patient with systemic lupus erythematosus: A diagnostic challenge

Resumen Mujer de 37 años con antecedentes de lupus eritematoso sistémico (LES), tromboembolia pulmonar y trombosis venosa profunda, quien consultó por dolor torácico, con hallazgos de elevación de la troponina, disfunción sistólica del ventrículo izquierdo y alteraciones de la contractilidad segmentaria, además de anti-DNA elevado y complemento consumido. La angiografía coronaria mostró estenosis grave en el tercio medio de la arteria descendente anterior, que fue intervenida con angioplastia más stent medicado. La resonancia magnética cardiaca reveló infarto agudo de miocardio extenso en el territorio de la arteria descendente anterior, sin miocarditis. Se descartó compromiso cardiaco por LES, se continuó igual terapia inmunosupresora, se añadió manejo para enfermedad coronaria y egresó por buena evolución. El enfoque de las causas de lesión miocárdica en un paciente con LES supone un reto, dadas las múltiples posibilidades en el espectro de compromiso cardiaco, ya que varias estructuras se pueden ver afectadas. La miocarditis y la pericarditis se consideran las más frecuentes, pero el compromiso coronario no puede descartarse, independientemente de la edad y de la presencia de factores de riesgo tradicionales, puesto que el componente inflamatorio de la patología autoinmunitaria confiere un desarrollo acelerado de ateroesclerosis. La multimodalidad diagnóstica y el enfoque interdisciplinario son necesarios para aclarar el mecanismo de la lesión y así brindar un tratamiento dirigido.

Abstract A 37-year-old woman with a history of systemic lupus erythematosus (SLE), pulmonary thromboembolism and deep vein thrombosis consulted for chest pain, with findings of elevated troponin, left ventricular systolic dysfunction, and segmental contractility abnormalities, as well as elevated anti-DNA and complement consumption. Coronary angiography showed severe stenosis of the middle third of the anterior descending artery, which was treated with angioplasty plus a medicated stent. Cardiac magnetic resonance imaging revealed an extensive acute myocardial infarction in the area supplied by the anterior descending artery, without myocarditis. Cardiac involvement in SLE was ruled out, immunosuppressive treatment was maintained, coronary disease treatment was added, and she was discharged due to improvement. Identifying the causes of myocardial insult in a patient with SLE is challenging, given the multiple possibilities across the cardiac involvement spectrum, in which several structures may be affected. Myocarditis and pericarditis are considered to be the most frequent, but coronary involvement cannot be ruled out, regardless of age or the presence of traditional risk factors, since the inflammatory component of the autoimmune disease accelerates the development of atherosclerosis. Multimodal diagnostics and an interdisciplinary approach are necessary to clarify the mechanism of injury and provide targeted treatment.

Sarcopenia and frailty in older adults hospitalized in internal medicine wards / Sarcopenia y fragilidad en adultos mayores hospitalizados en salas medicina interna

Abstract Introduction: sarcopenia and frailty are mutual risk clinical syndromes and adverse outcome indicators. There are currently no data in Latin America regarding the prevalence of these conditions in hospitalized patients. Objective: to determine the prevalence and clinical characteristics of patients age 65 and older with sarcopenia in internal medicine wards. Materials and methods: an observational, descriptive, prospective cross-sectional study, including men and women age 65 and older. The EWGSOP (European Working Group on Sarcopenia in Older People) and PRISMA 7 criteria were applied to determine sarcopenia and frailty, respectively. Results: out of 124 patients, 41.13% had sarcopenia, 34.68% had frailty and 18.55% had both. The median age was 74; 50.8% were women and 49.2% men. Conclusion: sarcopenia and frailty are highly prevalent in our population, with higher figures than those reported in the available literature. Subsequent studies may determine the effect of these conditions on clinical outcomes and costs. (Acta Med Colomb 2020; 45. DOI:https://doi.org/10.36104/amc.2020.1242)

Resumen Introducción: la sarcopenia y la fragilidad son síndromes clínicos de riesgo mutuo e indicadores de desenlaces adversos. Actualmente no hay datos en Latinoamérica sobre la prevalencia de estas condiciones en pacientes hospitalizados. Objetivo: determinar la prevalencia y características clínicas de los pacientes de 65 años o más con sarcopenia en salas de medicina interna. Material y métodos: estudio observacional, descriptivo, prospectivo, transversal. Incluyó hombres y mujeres de 65 años o más. Se aplicaron criterios de la EWGSOP (European Working Group on Sarcopenia in Older People) y PRISMA 7 para la determinación de sarcopenia y fragilidad respectivamente. Resultados: de 124 pacientes, 41.13% tenían sarcopenia, 34.68% fragilidad y las dos condiciones 18.55%. La mediana de edad fue 74 años, 50.8% mujeres y 49.2% hombres. Conclusión: la sarcopenia y la fragilidad tienen una alta prevalencia en nuestra población, cifras superiores a las reportadas en la literatura disponible. Estudios posteriores podrán determinar el efecto de estas condiciones en desenlaces clínicos y costos. (Acta Med Colomb 2020; 45. DOI:https://doi.org/10.36104/amc.2020.1242).

Sparing bilateral neck level IB in oropharyngeal carcinoma and xerostomia outcomes.

OBJECTIVES: To assess whether sparing neck-level IB in target delineation of node-positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes without compromising locoregional control (LRC). METHODS: A total of 125 N+ OPC patients with a median age of 57 years underwent chemoradiation between May 2010 and December 2011. A total of 74% of patients had T1-T2 disease, 26% T3-T4, 16% N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other. Patients were divided into those who had target delineation sparing of bilateral level IB (the spared cohort) versus no sparing (the treated cohort). Sparing of contralateral high-level II nodes was also performed more consistently in the spared cohort. A prospective xerostomia questionnaire (patient reported) was given at each patient follow-up visit to this cohort of patients to assess late xerostomia. Clinical assessment (observer rated) at each patient follow-up visit was also recorded. RESULTS: The 2-year LRC for the spared and treated cohorts was 97.5% and 93.8%, respectively (median follow-up, 23.2 mo). No locoregional failures occurred outside of treatment fields. The spared cohort experienced significant benefits in patient-reported xerostomia summary scores (P=0.021) and observer-rated xerostomia scores (P=0.006). In addition, there were significant reductions in mean doses to the ipsilateral submandibular gland (63.9 vs. 70.5 Gy; P<0.001), contralateral submandibular gland (45.0 vs. 56.2 Gy; P<0.001), oral cavity (35.9 vs. 45.2 Gy; P<0.001), and contralateral parotid gland (20.0 vs. 24.4 Gy; P<0.001). CONCLUSIONS: Target delineation sparing of bilateral level IB nodes in N+ OPC reduced mean doses to salivary organs without compromising LRC. Patients with reduced target volumes had better patient-reported xerostomia outcomes.

Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain.

BACKGROUND: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. OBJECTIVE: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. METHODS: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. RESULTS: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. CONCLUSION: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition.

INTRODUCCIÓN: La información de la expresión de genes consignada en bases de datos, ha permitido extraer y analizar información acerca procesos moleculares implicados tanto en la homeostasis cerebral y su alteración en algunas neuropatologías. OBJETIVOS: Correlacionar los niveles de transcripción de 19 genes localizados en la región crítica del cromosoma 21, asociada a Síndrome de Down (DSCR), con la localización cerebral y su coexpresión en diferentes subestructuras del cerebro humano. MÉTODOS: A partir de valores de expresión génica disponibles en la base de datos del proyecto cerebro humano del Atlas del Cerebro del "Allen Institute for Brain Sciences" (http://human.brain-map.org/), se construyeron perfiles de expresión de 19 genes DSCR en 42 subestructuras cerebrales. Además, utilizando métodos estadísticos multivariados se analizaron los patrones de coexpresión de genes DSCR en el cerebro normal. RESULTADOS: En el núcleo caudado, el núcleo accumbens y el putamen además de las Áreas centrales 2, 3 y 4, se determinaron los valores de expresión más elevados para los genes incluidos RCAN1, que codifica para una proteína involucrada en el proceso de transducción de señales de SNC; PCP4 cuya proteína interviene en la unión a la calmodulina y TTC3 una proteína que interviene en la diferenciación de neuronas. Las subestructuras identificadas con una elevada expresión de estos genes, están asociadas con procesos de aprendizaje, en diferentes tipos de memoria y habilidades motoras. CONCLUSIONES: La regulación de la expresión de los genes DSCR es clave para mantener la homeostasis cerebral, especialmente en aquellas áreas de mayor expresión, las cuales están asociadas con procesos sumamente importantes.

Terapia secuencial: una opción en el paciente hemofílico que no responde al manejo con monoterapia con agentes puente, estudio observacional del GrHeCol (Grupo Hemofilia Colombia) / Sequential therapy: an option for hemophiliac patients not responding to monotherapy with bypassing agents. Observational study of the GrHeCol (Grupo Hemofilia Colombia)

RESUMEN Introducción: la hemofilia A y B severa son condiciones que predisponen al sangrado espontáneo. Una de las complicaciones de la terapia con concentrados de factores de coagulación es el desarrollo de anticuerpos o inhibidores contra los factores VIII o IX. El tratamiento en casos de inhibidores de título alto, para el control de la hemorragia, es la administración de agentes puente como el complejo protrombínico activado y Factor VII recombinante activado. La respuesta a cada uno de ellos no es predecible, en algunos casos puede ser necesario el uso de la terapia secuencial cuando esta estrategia falla. Objetivo: reportar cinco casos de hemofilia A severa e inhibidores de título alto con sangrado severo, sin respuesta clínica con monoterapia y que recibieron terapia secuencial. Métodos: estudio multicéntrico, descriptivo, observacional. Las variables cualitativas se presentan con frecuencias absolutas y relativas, y las cuantitativas se resumen con medidas de tendencia central. Resultados: cuatro pacientes evaluados que aportaron cinco eventos, la mediana de edad 20 años; mediana de días de monoterapia 10; 8,6 días de terapia secuencial, tiempo a resolver el sangrado cuatro días. Ausencia de complicaciones trombóticas. Conclusiones: la terapia secuencial es una opción para aquellos pacientes que no responden a la monoterapia y requieren control hemostático. En los cinco casos reportados, la terapia secuencial logró controlar el sangrado sin complicaciones.

SUMMARY Introduction and objectives: Patients diagnosed with severe hemophilia are at risk of developing inhibitors of low or high title, being the treatment of choice for this latter group of patients the immune tolerance therapy (ITI). In cases where the immune tolerance fails or presents bleeding events, we can use activated prothrombin complex (APCC) or Recombinant activated factor VII (rFVIIa); however, patients may fail to these agents as monotherapy. The aim of this paper is to report five cases of severe hemophilia and high titer inhibitors with mayor bleeding, which fail to respond to monotherapy and required sequential therapy. Methods: Case report study, qualitative variables are presented as absolute and relative frequencies and quantitative are summarized with measures of central tendency. Results: Five patients with median age 20 years; monotherapy treatment with median 10 days; 8.6 days of sequential therapy, time to control the bleeding: 4 days. There were no thrombotic complications. Conclusions: Sequential therapy is an option for patients who do not respond to monotherapy and requires hemostatic control. In all the cases of this report, the patients were responsive with bleeding control.

Descripción de las caracteristicas clínicas de las neoplasias mieloproliferativas crónicas (NMPC). Primer informe del registro colombiano de NMPC / Description of the clinical characteristics of chronic myeloproliferative neoplasms (MPNs). First report of the colombian registry of MPNs

Resumen Introducción y objetivos: las neoplasias mieloproliferativas crónicas (NMPC) son relativamente raras, con incidencias que varían entre 0.47-1.03/100 000 habitantes. Se presenta el primer informe del trabajo del registro colombiano de NMPC, cuyo objetivo es describir las características clínicas de estos pacientes en nuestro país. Material y métodos: estudio descriptivo observacional, multicéntrico, retrospectivo y prospectivo en ocho centros del país, de abril de 2013 a diciembre de 2014. Las variables cualitativas se presentan con frecuencias absolutas y relativas; y las cuantitativas se resumen en medidas de tendencia central y dispersión. Resultados: once centros fueron aprobados, ocho ingresaron pacientes. En los primeros 179 casos reportados, 50% eran hombres, la edad promedio al diagnóstico 58.7 años (rango 19-92). Noventa y tres muestran trombocitemia esencial (TE); 55, policitemia vera (PV); y 31, mielofibrosis (MF). El 41% tenía esplenomegalia al diagnóstico; el 20% tuvo complicaciones trombóticas; y 12.85%, sangrado. Sólo en 57.5% se realizó JAK; de ellos, en 53.5% fue positivo, en especial sólo 60% de las PV. El 8% de los casos no tenía estudio de médula ósea, el 29.3% tiene algún grado de fibrosis. El hallazgo más frecuente fue hiperplasia megacariocítica en 59.78%. Más de 50% de pacientes estaban sintomáticos al diagnóstico. Sólo el 11% no recibió tratamiento farmacológico; los más frecuentes fueron hidroxiurea en 149 casos y ASA en 79. Con promedio de seguimiento de 52.6 meses; el 97.21% de los pacientes están vivos. Conclusiones: los hallazgos sugieren que algunas características de las NMPC podrían ser diferentes a lo reportado en otras series, lo que valida la importancia del esfuerzo de recoger información local.

Abstract Introduction and objectives: chronic MPNs are relatively rare, with incidences varying between 0.47-1.03 / 100 000 inhabitants. The first report of the work of the Colombian registry of chronic MPNs, whose objective is to describe the clinical characteristics of these patients in our country, is presented. Materials and methods: descriptive observational, multicenter, retrospective and prospective study in eight centers of the country, from April 2013 to December 2014. Qualitative variables are presented with absolute and relative frequencies, and the quantitative ones are summarized in measures of central tendency and dispersion. Results: eleven centers were approved; 8 admitted patients. In the first 179 cases reported, 50% were men; the average age at diagnosis was 58.7 years (range 19-92). Ninety-three present essential thrombocythemia (ET); 55, polycythemia vera (PV); and 31, myelofibrosis (MF). 41% had splenomegaly at diagnosis; 20% had thrombotic complications, and 12.85%, bleeding. JAK was performed in only 57.5%. Of them, in 53.5% was positive, especially in only 60% of the PV. 8% of the cases had no bone marrow study; 29.3% had some degree of fibrosis. The most frequent finding was megakaryocytic hyperplasia in 59.78%. More than 50% of patients were symptomatic at diagnosis. Only 11% did not receive pharmacological treatment, being the most frequent hydroxyurea in 149 cases and ASA in 79, with an average follow-up of 52.6 months. 97.21% of patients are alive. Conclusions: the findings suggest that some characteristics of chronic MPNs could be different from those reported in other series, which validates the importance of the effort to collect local information.