Immune dysregulation is an important factor in the underlying complications in Influenza infection. ApoH, IL-8 and IL-15 as markers of prognosis.

Introduction: Influenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression. Methods: We conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission. Results: Patients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C- reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis. RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71). Discussion: Therefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF.

Neurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study.

BACKGROUND: Neurological immune-related adverse events associated with immune checkpoint inhibitors can have several clinical manifestations, but the syndromes and prognostic factors are still not well known. We aimed to characterise and group the clinical features, with a special focus in patients presenting with encephalopathy, and to identify predictors of response to therapy and survival. METHODS: This retrospective observational study included patients with neurological immune-related adverse events from 20 hospitals in Spain whose clinical information, serum samples, and CSF samples were studied at Hospital Clinic de Barcelona, Barcelona, Spain. Patients with pre-existing paraneoplastic syndromes or evidence of alternative causes for their neurological symptoms were excluded. We reviewed the clinical information, classified their clinical features, and determined the presence of neural antibodies. Neurological status was assessed by the treating physician one month after adverse event onset (as improvement vs no improvement) and at the last evaluation (complete recovery or modified Rankin Scale score decrease of at least 2 points, indicating good outcome, vs all other modified Rankin Scale scores, indicating poor outcome); if the participant had died, the date and cause of death were recorded. We used Fisher's exact tests and Mann-Whitney U tests to analyse clinical features, and multivariable logistic regression to analyse prognostic factors. FINDINGS: From Jan 1, 2018, until Feb 1, 2023, 83 patients with suspected neurological immune-related adverse events after use of immune checkpoint inhibitors were identified, of whom 64 patients were included. These patients had a median age of 67 years (IQR 59-74); 42 (66%) were male and 22 (34%) were female. The predominant tumours were lung cancer (30 [47%] patients), melanoma (13 [21%] patients), and renal cell carcinoma (seven [11%] patients). Neural antibodies were detected in 14 (22%) patients; 52 (81%) patients had CNS involvement and 12 (19%) had peripheral nervous system involvement. Encephalopathy occurred in 45 (70%) patients, 12 (27%) of whom had antibodies or well defined syndromes consistent with definite paraneoplastic or autoimmune encephalitis, 24 (53%) of whom had encephalitis without antibodies or clinical features characteristic of a defined syndrome, and nine (20%) of whom had encephalopathy without antibodies or inflammatory changes in CSF or brain MRI. Nine (14%) of 64 patients had combined myasthenia and myositis, five of them with myocarditis. Even though 58 (91%) of 64 patients received steroids and 31 (48%) of 64 received additional therapies, 18 (28%) did not improve during the first month after adverse event onset, and 11 of these 18 people died. At the last follow-up for the 53 remaining patients (median 6 months, IQR 3-13), 20 (38%) had a poor outcome (16 deaths, one related to a neurological immune-related adverse event). Mortality risk was increased in patients with lung cancer (vs those with other cancers: HR 2·5, 95% CI 1·1-6·0) and in patients with encephalopathy without evidence of CNS inflammation or combined myocarditis, myasthenia, and myositis (vs those with the remaining syndromes: HR 5·0, 1·4-17·8 and HR 6·6, 1·4-31·0, respectively). INTERPRETATION: Most neurological immune-related adverse events involved the CNS and were antibody negative. The presence of myocarditis, myasthenia, and myositis, of encephalopathy without inflammatory changes, or of lung cancer were independent predictors of death. Most deaths occurred during the first month of symptom onset. If our findings are replicated in additional cohorts, they could confirm that these patients need early and intensive treatment. FUNDING: The Instituto de Salud Carlos III and the European Union.

Frequency and Referral Patterns of Neural Antibody Studies During the COVID-19 Pandemic: Experience From an Autoimmune Neurology Center.

OBJECTIVE: To determine whether the frequency of paraneoplastic or autoimmune encephalitis antibodies examined in a referral center changed during the COVID-19 pandemic. METHODS: The number of patients who tested positive for neuronal or glial (neural) antibodies during pre-COVID-19 (2017-2019) and COVID-19 (2020-2021) periods was compared. The techniques used for antibody testing did not change during these periods and included a comprehensive evaluation of cell-surface and intracellular neural antibodies. The chi-square test, Spearman correlation, and Python programming language v3 were used for statistical analysis. RESULTS: Serum or CSF from 15,390 patients with suspected autoimmune or paraneoplastic encephalitis was examined. The overall positivity rate for antibodies against neural-surface antigens was similar in the prepandemic and pandemic periods (neuronal 3.2% vs 3.5%; glial 6.1 vs 5.2) with a mild single-disease increase in the pandemic period (anti-NMDAR encephalitis). By contrast, the positivity rate for antibodies against intracellular antigens was significantly increased during the pandemic period (2.8% vs 3.9%, p = 0.01), particularly Hu and GFAP. DISCUSSION: Our findings do not support that the COVID-19 pandemic led to a substantial increase of known or novel encephalitis mediated by antibodies against neural-surface antigens. The increase in Hu and GFAP antibodies likely reflects the progressive increased recognition of the corresponding disorders.

Algorithm to improve the diagnosis of paraneoplastic neurological syndromes associated with SOX1 antibodies.

SOX1 antibodies (SOX1-abs) are associated with paraneoplastic neurological syndromes (PNS) and small cell lung cancer (SCLC). In many clinical laboratories SOX1-abs are determined by commercial line blots without confirmation by cell-based assay (CBA) with HEK293 cells expressing SOX1. However, the diagnostic yield of commercial line blots is low and the accessibility to the CBA, that is not commercially available, limited. Here, we evaluated if the addition of the band intensity data of the line blot and the immunoreactivity in a tissue-based assay (TBA) improve the diagnostic performance of the line blot. We examined serum of 34 consecutive patients with adequate clinical information that tested positive for SOX1-abs in a commercial line blot. Samples were also assessed by TBA and CBA. SOX1-abs were confirmed by CBA in 17 (50%) patients, all (100%) had lung cancer (SCLC in 16) and 15/17 (88%) had a PNS. In the remaining 17 patients the CBA was negative and none had PNS associated with lung cancer. TBA was assessable in 30/34 patients and SOX1-abs reactivity was detected in 15/17 (88%) with positive and in 0/13 (0%) with negative CBA. Only 2 (13%) of the 15 TBA-negative patients were CBA-positive. The frequency of TBA-negative but CBA-positive increased from 10% (1/10) when the band intensity of the line blot was weak to 20% (1/5) in patients with a moderate or strong intensity band. Confirmation by CBA should be mandatory for samples (56% in this series) not assessable (4/34; 12%) or negative in the TBA (15/34; 44%).

The diagnosis of anti-LGI1 encephalitis varies with the type of immunodetection assay and sample examined.

Detection of Leucine-rich glioma inactivated 1 (LGI1) antibodies in patients with suspected autoimmune encephalitis is important for diagnostic confirmation and prompt implementation of immunomodulatory treatment. However, the clinical laboratory diagnosis can be challenging. Previous reports have suggested that the type of test and patient's sample (serum or CSF) have different clinical performances, however, there are no studies comparing different diagnostic tests on paired serum/CSF samples of patients with anti-LGI1 encephalitis. Here, we assessed the clinical performance of a commercial and an in house indirect immunofluorescent cell based assays (IIF-CBA) using paired serum/CSF of 70 patients with suspected anti-LGI1 encephalitis and positive rat brain indirect immunohistochemistry (IIHC). We found that all (100%) patients had CSF antibodies when the in house IIF-CBA was used, but only 88 (83%) were positive if the commercial test was used. In contrast, sera positivity rate was higher with the commercial test (94%) than with the in house assay (86%). If both serum and CSF were examined with the commercial IIFA-CBA, 69/70 (98.5%) patients were positive in at least one of the samples. These findings are clinically important for centers in which rat brain IIHC and in house IIFA-CBA are not available. Moreover, the observation that all patients with anti-LGI1 encephalitis have antibodies in CSF is in line with the concept that these antibodies are pathogenic.

Limitations of a Commercial Assay as Diagnostic Test of Autoimmune Encephalitis.

Detection of neuronal surface antibodies (NSAb) is important for the diagnosis of autoimmune encephalitis (AE). Although most clinical laboratories use a commercial diagnostic kit (Euroimmun, Lübeck, Germany) based on indirect immunofluorescence on transfected cells (IIFA), clinical experience suggests diagnostic limitations. Here, we assessed the performance of the commercial IIFA in serum and CSF samples of patients with suspected AE previously examined by rat brain immunohistochemistry (Cohort A). Of 6213 samples, 404 (6.5%) showed brain immunostaining suggestive of NSAb: 163 (40%) were positive by commercial IIFA and 241 (60%) were negative. When these 241 samples were re-assessed with in-house IIFA, 42 (18%) were positive: 21 (9%) had NSAb against antigens not included in the commercial IIFA and the other 21 (9%) had NSAb against antigens included in the commercial kit (false negative results). False negative results occurred more frequently with CSF (29% vs 10% in serum) and predominantly affected GABABR (39%), LGI1 (17%) and AMPAR (11%) antibodies. Results were reproduced in a separate cohort (B) of 54 AE patients with LGI1, GABABR or AMPAR antibodies in CSF which were missed in 30% by commercial IIFA. Patients with discordant GABABR antibody results (positive in-house but negative commercial IIFA) were less likely to develop full-blown clinical syndrome; no significant clinical differences were noted for the other antibodies. Overall, NSAb testing by commercial IIFA led to false negative results in a substantial number of patients, mainly those affected by anti-LG1, GABABR or AMPAR encephalitis. If these disorders are suspected and commercial IIFA is negative, more comprehensive antibody studies are recommended.

Thymoma and Autoimmune Encephalitis: Clinical Manifestations and Antibodies.

OBJECTIVE: To report the clinical, neuroimaging, and antibody associations in patients with autoimmune encephalitis (AE) and thymoma. METHODS: A retrospective cohort study of 43 patients was conducted. Antibody determination and immunoprecipitation to characterize novel antigens were performed using reported techniques. RESULTS: Patients' median age was 52 years (range: 23-88 years). Forty (93%) had neuronal surface antibodies: gamma-aminobutyric acid receptor A (GABAAR) (15), amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) (13), contactin-associated protein-like 2 (CASPR2) (4), leucine-rich, glioma inactivated 1 (LGI1) (3), glycine receptor (GlyR) (3), and unknown antigens (2). Concurrent antibodies against intracellular antigens occurred in 13 (30%; 9 anti-collapsin response mediator protein 5 [CRMP5]) and were more frequent in anti-AMPAR encephalitis (54% vs 20%; p = 0.037). The most common clinical presentation was encephalitis with multiple T2/fluid-attenuated inversion recovery hyperintense lesions in 23 (53%) patients (15 GABAAR, 5 AMPAR, and 1 unknown neuropil antibody), followed by encephalitis with peripheral nerve hyperexcitability in 7 (16%; 4 CASPR2, 2 LGI1, and 1 unknown antibody), limbic encephalitis in 6 (14%; 4 AMPAR, 1 LGI1, and 1 antibody negative), progressive encephalomyelitis with rigidity and myoclonus in 4 (9%; 3 GlyR and 1 AMPAR antibodies), and encephalitis with normal MRI in 3 (7%; AMPAR antibodies). Anti-GABAAR encephalitis was more prevalent in Japanese patients compared with Caucasians and other ethnicities (61% vs 16%; p = 0.003). In anti-AMPAR encephalitis, 3/4 patients with poor and 0/6 with good outcome had concurrent CRMP5 antibodies (p = 0.033). Immunoprecipitation studies identified metabotropic glutamate receptor 3 antibodies that were additionally found in 5 patients (3 with and 2 without encephalitis). CONCLUSIONS: AE in patients with thymoma include several clinical-radiologic syndromes that vary according to the associated antibodies. Anti-GABAAR encephalitis was the most frequent AE and occurred more frequently in Japanese patients.

Presence of Extra-Criteria Antiphospholipid Antibodies Is an Independent Risk Factor for Ischemic Stroke.

Background: Ischemic stroke is the most common and severe arterial thrombotic event in Antiphospholipid syndrome (APS). APS is an autoimmune disease characterized by the presence of thrombosis and antiphospholipid antibodies (aPL), which provide a pro-coagulant state. The aPL included in the classification criteria are lupus anticoagulant, anti-cardiolipin (aCL) and anti-ß2-glycoprotein-I antibodies (aB2GPI) of IgG and IgM isotypes. Extra-criteria aPL, especially IgA aB2GPI and IgG/IgM anti-phosphatidylserine/prothrombin antibodies (aPS/PT), have been strongly associated with thrombosis. However, their role in the general population suffering from stroke is unknown. We aim (1) to evaluate the aPL prevalence in ischemic stroke patients, (2) to determine the role of aPL as a risk factor for stroke, and (3) to create an easy-to-use tool to stratify the risk of ischemic stroke occurrence considering the presence of aPL and other risk factors. Materials and Methods: A cohort of 245 consecutive ischemic stroke patients was evaluated in the first 24 h after the acute event for the presence of classic aPL, extra-criteria aPL (IgA aB2GPI, IgG, and IgM aPS/PT) and conventional cardiovascular risk factors. These patients were followed-up for 2-years. A group of 121 healthy volunteers of the same age range and representative of the general population was used as reference population. The study was approved by the Ethics Committee for Clinical Research (Reference numbers CEIC-14/354 and CEIC-18/182). Results: The overall aPL prevalence in stroke patients was 28% and IgA aB2GPI were the most prevalent (20%). In the multivariant analysis, the presence of IgA aB2GPI (OR 2.40, 95% CI: 1.03-5.53), dyslipidemia (OR 1.70, 95% CI: 1.01-2.84), arterial hypertension (OR 1.82, 95% CI: 1.03-3.22), atrial fibrillation (OR 4.31, 95% CI: 1.90-9.78), and active smoking (OR 3.47, 95% CI: 1.72-6.99) were identified as independent risk factors for ischemic stroke. A risk stratification tool for stroke was created based on these factors (AUC: 0.75). Conclusions: IgA aB2GPI are an important independent risk factor for ischemic stroke. Evaluation of aPL (including extra-criteria) in cardiovascular risk factor assessment for stroke can potentially increase the identification of patients at risk of thrombotic event, facilitating a decision on preventive treatments.

IL-6-based mortality risk model for hospitalized patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic. Because the severity of the disease is highly variable, predictive models to stratify patients according to their mortality risk are needed. OBJECTIVE: Our aim was to develop a model able to predict the risk of fatal outcome in patients with COVID-19 that could be used easily at the time of patients' arrival at the hospital. METHODS: We constructed a prospective cohort with 611 adult patients in whom COVID-19 was diagnosed between March 10 and April 12, 2020, in a tertiary hospital in Madrid, Spain. The analysis included 501 patients who had been discharged or had died by April 20, 2020. The capacity of several biomarkers, measured at the beginning of hospitalization, to predict mortality was assessed individually. Those biomarkers that independently contributed to improve mortality prediction were included in a multivariable risk model. RESULTS: High IL-6 level, C-reactive protein level, lactate dehydrogenase (LDH) level, ferritin level, d-dimer level, neutrophil count, and neutrophil-to-lymphocyte ratio were all predictive of mortality (area under the curve >0.70), as were low albumin level, lymphocyte count, monocyte count, and ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2). A multivariable mortality risk model including the SpO2/FiO2 ratio, neutrophil-to-lymphocyte ratio, LDH level, IL-6 level, and age was developed and showed high accuracy for the prediction of fatal outcome (area under the curve 0.94). The optimal cutoff reliably classified patients (including patients with no initial respiratory distress) as survivors and nonsurvivors with 0.88 sensitivity and 0.89 specificity. CONCLUSION: This mortality risk model allows early risk stratification of hospitalized patients with COVID-19 before the appearance of obvious signs of clinical deterioration, and it can be used as a tool to guide clinical decision making.

Perfil cardiovascular en pacientes con disfunción eréctil tratados en un centro de alta complejidad en la ciudad de Medellín, Colombia / Cardiovascular Profile in Patients with Erectile Dysfunction Treated in a High Complexity Center in Medellín City, Colombia

Objetivo Determinar el perfil cardiovascular de los pacientes con disfunción eréctil en un centro de alta complejidad de Medellín. Métodos Estudio descriptivo, retrospectivo, en el que se incluyeron pacientes con diagnóstico de disfunción eréctil confirmado por el departamento de Urología, tratados en un centro de alta complejidad de Medellín entre 2010 y 2017; excluyendo aquellos con historia clínica con información incompleta o con desenlace cardiovascular previo al diagnóstico de disfunción eréctil. Los datos se obtuvieron de fuentes secundarias y se realizó su registro en una base de datos para su análisis mediante paquete estadístico (SPSS 24 Inc, Chicago, IL). Resultados Se captaron, durante el periodo de estudio, 67 pacientes con disfunción eréctil que cumplieron los criterios de elegibilidad. Con una media de edad de 47,5 años. El 82% presentó disfunción eréctil severa, que estuvo asociada con el antecedente de angina, enfermedad coronaria y síndrome coronario agudo. Así mismo, más del 80% de los pacientes con diabetes, hipertensión, dislipidemia, tabaquismo, enfermedad renal crónica, obesidad y alcoholismo considerados como marcadores importantes de riesgo cardiovascular, presentaron disfunción eréctil severa. Conclusión La comorbilidad cardiovascular en pacientes con DE es alta, existiendo una relación al compartir factores de riesgo y vías fisiopatológicas. Los pacientes con DE severa presentan mayor número de patologías asociadas, volviéndolos más propensos a desenlaces cardio-cerebrovasculares.

Objective To determine the cardiovascular profile of patients with erectile dysfunction in a high complexity center in Medellín. Methods Descriptive, retrospective study, in patients diagnosed with erectile dysfunction confirmed by the Department of Urology, treated in a high complexity center of Medellín between 2010 and 2017; excluding those with a clinical history with incomplete information or with a cardiovascular outcome prior to the diagnosis of erectile dysfunction. The data were obtained from secondary sources and their registration was made in a database for analysis by statistical package (SPSS 24 Inc, Chicago, IL). Results 67 patients with erectile dysfunction were selected during the study period, who met the eligibility criteria. With an average age of 47.5 years. 82% had severe erectile dysfunction, and it was associated with a history of angina, coronary disease and acute coronary syndrome. Likewise, more than 80% of patients with diabetes, hypertension, dyslipidemia, smoking, chronic kidney disease, obesity and alcoholism, considered important markers of cardiovascular risk, presented severe erectile dysfunction. Conclusion Cardiovascular comorbidity in patients with ED is high, there is a relationship, sharing risk factors and pathophysiological pathways. Patients with severe ED have a greater number of associated pathologies, making them more prone to cardio-cerebrovascular outcomes.

Bloqueo de rama izquierda como equivalente ST, ¿cuándo sí, cuándo no? / Left bundle branch block as equivalent of ST-segment elevation myocardial infarction: when yes, when not?

Resumen La presencia de un bloqueo de rama izquierda del haz de His nuevo o presumiblemente nuevo junto con síntomas isquémicos se ha considerado tradicionalmente un equivalente electrocardiográfico de infarto agudo de miocardio con elevación del segmento ST, el cual debe ser llevado a reperfusión emergente. Para su definición se han propuesto varios criterios, pero ninguno ha alcanzado un rendimiento diagnóstico óptimo. A continuación detallaremos dichos criterios, sus principales problemas y las ventajas que han demostrado.

Abstract A new or presumably new left bundle branch block along with ischemic symptoms has traditionally been considered an electrocardiographic equivalent of ST-segment elevation myocardial infarction, which should be brought to emergent reperfusion. However, several criteria have been proposed for its definition, but none has reached out an optimal diagnostic yield. Below we detail these criteria, their main problems and the advantages they have shown.

Health economic evaluation of Human Papillomavirus vaccines in women from Venezuela by a lifetime Markov cohort model.

BACKGROUND: Cervical cancer (CC) and genital warts (GW) are a significant public health issue in Venezuela. Our objective was to assess the cost-effectiveness of the two available vaccines, bivalent and quadrivalent, against Human Papillomavirus (HPV) in Venezuelan girls in order to inform decision-makers. METHODS: A previously published Markov cohort model, informed by the best available evidence, was adapted to the Venezuelan context to evaluate the effects of vaccination on health and healthcare costs from the perspective of the healthcare payer in an 11-year-old girls cohort of 264,489. Costs and quality-adjusted life years (QALYs) were discounted at 5%. Eight scenarios were analyzed to depict the cost-effectiveness under alternative vaccine prices, exchange rates and dosing schemes. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Compared to screening only, the bivalent and quadrivalent vaccines were cost-saving in all scenarios, avoiding 2,310 and 2,143 deaths, 4,781 and 4,431 CCs up to 18,459 GW for the quadrivalent vaccine and gaining 4,486 and 4,395 discounted QALYs respectively. For both vaccines, the main determinants of variations in the incremental costs-effectiveness ratio after running deterministic and probabilistic sensitivity analyses were transition probabilities, vaccine and cancer-treatment costs and HPV 16 and 18 distribution in CC cases. When comparing vaccines, none of them was consistently more cost-effective than the other. In sensitivity analyses, for these comparisons, the main determinants were GW incidence, the level of cross-protection and, for some scenarios, vaccines costs. CONCLUSIONS: Immunization with the bivalent or quadrivalent HPV vaccines showed to be cost-saving or cost-effective in Venezuela, falling below the threshold of one Gross Domestic Product (GDP) per capita (104,404 VEF) per QALY gained. Deterministic and probabilistic sensitivity analyses confirmed the robustness of these results.

Cáncer de mama: la enfermedad del siglo XXI / Breast cancer: the disease of the 21st century

El cáncer de mama es considerado en la actualidad como una de las patologías más comunes en la población femenina. Su incidencia va en aumento y se asocia a factores de riesgo tales como la edad, el sexo, factores hormonales y antecedentes tanto familiares como personales. Se ha asociado también a ciertos genes (BRCA 1 y BRCA 2), pero en su patogenia están involucrados otros factores como la dieta, el consumo de alcohol y la hiperinsulinemia. El diagnóstico debe ser abordado desde tres lineamientos: clínico, imagenológico e inmunohistoquímico, pues el tratamiento y el pronóstico dependen de la clasificación definitiva del tumor.

Breast cancer is currently considered as one of the most common pathologies in female population. Incidence is increasing and is associated with risk factors such as age, sex, hormonal factors and both family and personal history. It has also been associated with certain genes (BRCA 1 and BRCA 2), but factors such as diet, alcohol consumption and hyperinsulinemia are also involved in its pathogenesis. The diagnosis must be approached from three guidelines: clinical, imaging and immunohistochemical because the treatment and prognosis depend from the definitive classification of the tumor

Diagnóstico y tratamiento de la neutropenia febril en niños con cáncer: Consenso de la Sociedad Latinoamericana de Infectología Pediátrica / Diagnosis and treatment of febrile neutropenia in pediatric cancer patients: Consensus of the Sociedad Latinoamericana de Infectología Pediátrica

La Sociedad Latinoamericana de Infectología Pediátrica, a través de su Comité de Infecciones en Niños Inmunocomprometidos, propone un documento de consenso sobre "Diagnóstico y tratamiento de la neutropenia febril en niños con cáncer". Este documento-guía aborda el manejo de la neutrope-nia febril orientado a la atención de niños con cáncer en América Latina. Se realizó una búsqueda exhaustiva de la literatura, y se consideró particularmente la experiencia publicada proveniente de centros de nuestro continente, que aporta una mirada regional y adecuada a la realidad de nuestros países. El manuscrito contiene un panorama epidemiológico de la Región y recomendaciones para la evaluación clínica y de laboratorio necesarios para el manejo de estos pacientes, establece criterios de categorización de riesgo de infecciones bacterianas invasoras, analiza las medidas de cuidado general de los pacientes en el ambiente hospitalario y extra-hospitalario, propone diferentes enfoques terapéuticos de acuerdo a las realidades epidemiológicas institucionales, parámetros clínicos y de categorización de riesgo, establece diferentes algoritmos de seguimiento según la evolución de cada paciente, especifica las situaciones en que está indicada algún tipo de profilaxis y da los lineamientos generales sobre el tipo y oportunidad de terapia antifúngica a utilizar en ellos. Se ha puesto especial énfasis en entregar, de forma práctica, y con la mayor evidencia posible, las recomendaciones para el mejor manejo de los niños con cáncer, fiebre y neutropenia, buscando la equidad y la excelencia en todos los centros oncológicos latinoamericanos.

This document is a consensus guideline on the "Diagnosis and treatment of febrile neutropenia in children with cancer" developed by the Committee for Infectious Diseases in Immunocompromised Children of the Sociedad Latinoamericana de Infectología Pediátrica. This guideline discusses the management of febrile neutropenia focused on Latin American children with cancer. It is based on a thorough review of the literature, with particular attention to experiences reported by centers within the continent in order to provide recommendations applicable to the region. The manuscript includes a description of the regional epidemiology of cancer and infections in children, recommendations for clinical and laboratory studies required for patient management, description of a classification method to identify patients at different risk for invasive bacterial infections, outpatient and inpatient general care strategies and differential treatment strategies adjusted to local epidemiological realities, different algorithms for patient follow-up according to clinical course, a discussion of the rationale for prophylaxis strategies in specific situations including general guidelines for antifungal treatment. The Guidelines intend to provide practical, evidence-based recommendations in order to promote the best possible management for children with cancer, fever and neutropenia, throughout oncology centers of Latin America.

Prevalence of antiretroviral drug resistance among treatment-naive and treated HIV-infected patients in Venezuela

An in-house, low-cost method was developed to determine the genotypic resistance of immunodeficiency virus type 1 (HIV-1) isolates. All 179 Venezuelan isolates analysed belonged to subtype B. Primary drug resistance mutations were found in 11 percent of 63 treatment-naïve patients. The prevalence of resistance in isolates from 116 HIV-positive patients under antiretroviral treatment was 47 percent to protease inhibitors, 65 percent to nucleoside inhibitors and 38 percent to non-nucleoside inhibitors, respectively. Around 50 percent of patients in the study harboured viruses with highly reduced susceptibility to the three classical types of drugs after only five years from their initial diagnoses.

Transplante hepático pediátrico en Venezuela experiencia preliminar

Introducción y objetivos: el transplante hepático es uno de los tratamientos adecuados en pacientes pediátricos con enfermedades hepáticas en fase terminal. El objetivo del presente trabajo es presentar la experiencia preliminar del programa de transplante hepático pediátrico llevada a cabo en nuestro país. Pacientes y métodos: se incluyeron niños que fueron evaluados en la consulta de pretransplante pediátrico del programa metropolitano de transplante por presentar enfermedades hepáticas en fase terminal Resultados: se incluyeron pacientes a los que se les realizó transplante hepático entre abril de 2005 y marzo de 2007; 9 pacientes en edades comprendidas entre 5 años y 15 años, 3 del sexo masculino y 6 del sexo femenino. Todos los pacientes presentaban serología para CMV positiva previo al transplante y 5 presentaban serología positiva para EBV previa al transplante. Todos los individuos tenían una calificación PELD entre 9 y 17. La enfermedad hepática crónica que los llevó a la necesidad de realizarles transplante hepático incluyó los siguientes diagnósticos: atresia de vías biliares extrahepáticas4, colestasis intrahepática familiar progresiva² y hepatitis autoinmune¹, hepatocarcinoma¹ y fibrosis hepática congénita¹. A 7 de los pacientes se les realizó transplante hepático de donante vivo, 1 de donante cadavérico y 1 autotransplante. El tiempo de estadía en terapia intensiva fue de 11 a 30 días, y el tiempo posterior en hospitalización fue de 3 a 15 días. El esquema de inmunosupresión inicial fue ciclosporina, prednisona, micofenolato a 4 pacientes y 5 tacrolimus y prednisona. Dos pacientes presentaron rechazo agudo el cual fue tratado con bolus de esteroides por 3 días con resolución completa de la disfunción del injerto. Todos los pacientes presentaron complicaciones infecciosas en los primeros 6 meses del postransplante, entre ellas: 4 pacientes infecciones urinarias documentadas por urocultivo por Proteus Mirabilis 2 y E. Coli 2, 5 pacientes presentaron infecciones por CMV a los cuales se les administró valganciclovir por vía oral obteniendo una respuesta adecuada. Dos de los pacientes presentaron complicaciones neurológicas, 1 presentó convulsiones tónico clónicas generalizadas sin déficit neurológico, se le realizó TAC y EEG los cuales resultaron normales con niveles elevados de ciclosporina y niveles bajos de magnesio que fueron corregidos. Un paciente presentó alucinaciones, se le realizó TAC cerebral y EEG normal, recibió haloperidol durante un período de 3 meses, con evolución satisfactoria. Uno de los pacientes presentó complicación biliar a los 9 meses postransplante, demostrada por ecografía abdominal y colangioresonancia (estenosis de la vía biliar), se colocó prótesis biliar con mejoría completa del funcionalismo hepático. Un paciente con síndrome hepatopulmonar previo al transplante, amerito para su corrección final, después del trasplante de tratamiento endovascular del shunt AV, arteria pulmonar lóbulo inferior izquierdo con colocación de espirales de titanium con resolución de la hipoxemia persistente. Posteriormente, ese mismo paciente presentó vasoespasmo de la arteria hepática documentado por perdida del registro arterial durante evaluación doppler y acompañado de elevación de las aminotranferasas recibiendo tratamiento con nitroglicerina intrarterial y colocación de stent con mejoría completa del funcionalismo hepático. La sobrevida del injerto y de los pacientes es en la actualidad de un 100%. Conclusión: el transplante hepático constituye hoy en día en Venezuela una posibilidad terapéutica para los pacientes pediátricos con enfermedad hepática terminal, progresiva e irreversible, que no está exento de complicaciones pero que al ser diagnosticadas y tratadas a tiempo, alcanza un 100% de sobrevida tanto del injerto como de los pacientes.

Introduction and Objectives: Liver transplantation is the treatment of choice for pediatrics patients that suffer end stage liver disease (ESLD). The goal of this essay is to introduce the first national experience with the modality of liver pediatric transplantation programs in the treatment of ESLD in pediatrics patients. Patients and Methods: 9 children suffering ESLD and their respective donors were seen between April 2005 and May 2007, each patient and its donor underwent a complete transplant evaluation (cardiac, respiratory, renal evaluation, imaging studies, and blood work up) to determine their candidate for either liver transplant recipient, or liver donor. RESULTS: 9 patients in ages between 5 years and 15 years, 3 male and 6 were included. All the patients had positive serology for CMV before transplant and 5 had positive serology for EBV before transplant. All the patients had score PELD 9 and 17. Diagnoses of the recipients were as follow: 4 Atresias of extrahepatic biliary tract, 2 progressive familiar intrahepatic cholestasis, 1 autoimmune hepatitis, 1 congenital fibrosis and 1 hepatocarcinoma. 7 live donor liver transplants, 1 deceased donor and 1 autologous liver transplant were performed. Operative mortality was 0%. Patient and graft survival were 100% at 1 and 2 years follow up. Patients presented various complications that included: acute rejection, CMV infection, acute urinary tract infections, hepatic artery spasm, and seizures among others. All the previous mentioned complications were successfully treated. Conclusion: Liver transplant constitutes the best option for the patient with ESLD, early referral is critical in the outcome of pediatric patients that need liver transplant.