Clinical practice guideline on the management of vestibular schwannoma.

INTRODUCTION: Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle. The greater accessibility to radiological tests has increased its diagnosis. Taking into account the characteristics of the tumour, the symptoms and the age of the patient, three therapeutic strategies have been proposed: observation, surgery or radiotherapy. Choosing the most appropriate for each patient is a frequent source of controversy. MATERIAL AND METHODS: This paper includes an exhaustive literature review of issues related to VS that can serve as a clinical guide in the management of patients with these lesions. The presentation has been oriented in the form of questions that the clinician usually asks himself and the answers have been written and/or reviewed by a panel of national and international experts consulted by the Otology Commission of the SEORL-CCC. RESULTS: A list has been compiled containing the 13 most controversial thematic blocks on the management of VS in the form of 50 questions, and answers to all of them have been sought through a systematic literature review (articles published on PubMed and Cochrane Library between 1992 and 2023 related to each thematic area). Thirty-three experts, led by the Otology Committee of SEORL-CCC, have analyzed and discussed all the answers. In Annex 1, 14 additional questions divided into 4 thematic areas can be found. CONCLUSIONS: This clinical practice guideline on the management of VS offers agreed answers to the most common questions that are asked about this tumour. The absence of sufficient prospective studies means that the levels of evidence on the subject are generally medium or low. This fact increases the interest of this type of clinical practice guidelines prepared by experts.

Cytokine profiling and transcriptomics in mononuclear cells define immune variants in Meniere Disease.

Meniere Disease (MD) is a chronic inner ear disorder characterized by vertigo attacks, sensorineural hearing loss, tinnitus, and aural fullness. Extensive evidence supporting the inflammatory etiology of MD has been found, therefore, by using transcriptome analysis, we aim to describe the inflammatory variants of MD. We performed Bulk RNAseq on 45 patients with definite MD and 15 healthy controls. MD patients were classified according to their basal levels of IL-1ß into 2 groups: high and low. Differentially expression analysis was performed using the ExpHunter Suite, and cell type proportion was evaluated using the estimation algorithms xCell, ABIS, and CIBERSORTx. MD patients showed 15 differentially expressed genes (DEG) compared to controls. The top DEGs include IGHG1 (p = 1.64 × 10-6) and IGLV3-21 (p = 6.28 × 10-3), supporting a role in the adaptative immune response. Cytokine profiling defines a subgroup of patients with high levels of IL-1ß with up-regulation of IL6 (p = 7.65 × 10-8) and INHBA (p = 3.39 × 10-7) genes. Transcriptomic data from peripheral blood mononuclear cells support a proinflammatory subgroup of MD patients with high levels of IL6 and an increase in naïve B-cells, and memory CD8+ T cells.

Sudden Hearing Loss as an Initial Symptom of Vestibular Schwannoma.

OBJECTIVE: This study aims to determine the prevalence of vestibular schwannoma (VS) among patients presenting with sudden hearing loss (SHL) and to characterize the clinical features of individuals diagnosed with both VS and SHL. METHODS: We conducted an observational retrospective review at a tertiary referral center, spanning a 30-year period, focusing on patients diagnosed with SHL where VS was confirmed as the underlying cause. We included patients meeting these criteria while excluding those lacking imaging or with a pre-existing diagnosis of VS. We evaluated the audiological characteristics at the time of diagnosis and assessed clinical outcomes following treatment. RESULTS: Among the 403 patients presenting with SHL during the study period, 9 (2.2%) were diagnosed with VS, aged between 25 and 72 years. Although audiometric profiles varied, high-frequency hearing loss predominated, mostly categorized as mild to moderate. Six patients (66%) had Koos grade I-II schwannomas. Only 2 patients achieved complete hearing recovery post-treatment, while 4 showed no improvement. CONCLUSIONS: VS is a rare etiology of SHL, accounting for slightly over 2% of cases. Its symptomatology, severity, and audiometric patterns do not significantly differ from SHL caused by other factors. Tumor size does not correlate with hearing characteristics. Treatment modalities resemble those for other SHL cases, and hearing improvement does not obviate the necessity for follow-up magnetic resonance imaging (MRI) scans.

Persistence with long-term PCSK9 inhibitor treatment and its effectiveness in familial hypercholesterolaemia: data from the SAFEHEART study.

AIMS: Most heterozygous familial hypercholesterolaemia (FH) patients require intensive lipid-lowering therapy (LLT) including PCSK9 inhibitors (PCSK9is) to reach current low-density lipoprotein cholesterol (LDL-C) goals. Persistence with chronic treatment is important to reduce the burden of atherosclerotic cardiovascular disease. We analysed persistence, efficacy, and impact on quality of life (QoL) of PCSK9i in FH patients in clinical practice setting. METHODS AND RESULTS: Spanish Familial Hypercholesterolaemia Cohort Study (SAFEHEART) is an open, prospective study in genetically defined FH patients in Spain. Patients ≥18 years of age (n = 696, 46% females) on stable LLT treated with PCSK9i were analysed. Median LDL-C at starting PCSK9i was 145 mg/dL [interquartile range (IQR), 123-177], 3.8 mmol/L (IQR 3.2-4.6). After a median follow up of 3.7 years (IQR 2.3-4.8), 27 patients (4%) discontinued PCSK9i treatment: 5 temporarily (0.7%) and 22 permanently (3.2%). Persistence with PCSK9i was 96.1% in the whole period. Median LDL-C levels and % LDL-C reduction attained after 1 year of treatment and in the last follow-up visit were 63 mg/dL (IQR 43-88), 1.6 mmol/L (IQR 1.1-2.23); 61 mg/dL (IQR 44-82), 1.6 mmol/L (IQR 1.1-2.1); 57.6% (IQR 39.5-69); and 58% (IQR 44-68), respectively. 2016 and 2019 ESC/EAS LDL-C goals were attained by 77 and 48% of patients, respectively, at the last follow-up visit (P < 0.001). Mean QoL score increased slightly in the first year and remained stable. CONCLUSION: Long-term persistence with PCSK9i in FH patients is very high, with a good QoL. Effectiveness in LDL-C reduction and LDL-C goal achievement dramatically improved with PCSK9i in this high-risk population in clinical practice setting. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02693548.

Checklist of the temporal bone and lateral skull base CT-scan.

Computed tomography scan of the temporal bone is a fundamental imaging modality for both the diagnosis and treatment of a wide range of pathologies affecting this complex structure. Temporal bone computed tomography scan provides a more detailed depiction of bone structures, compared with magnetic resonance imaging and, for this reason computed tomography scan is the imaging modality of choice in the planning of otological surgery. The aim of this article is to present a checklist to allow the otolaryngologist to assess systematically and in an organized manner the main anatomical landmarks, anatomical variants, as well as the most common postoperative surgical changes, which can be identified before any safe otological surgery. This revision was promoted by the Spanish Society of Otolaryngology and elaborated in a checklist template divided into the different areas of the temporal bone and the lateral skull base.

Efficacy of PCSK9 inhibitors in the treatment of heterozygous familial hypercholesterolemia: A clinical practice experience.

BACKGROUND: PCSK9 inhibitors are a treatment option for patients with familial hypercholesterolemia not on low-density lipoprotein cholesterol goals despite the use of maximally tolerated high intensity-statins dose. OBJECTIVE: To evaluate the efficacy of alirocumab and evolocumab in LDL-C reduction and targets attainment in patients with heterozygous familial hypercholesterolemia in clinical practice setting. METHODS: SAFEHEART is an open, long-term prospective study of a cohort of subjects with molecular diagnosis of familial hypercholesterolemia. This study analyze subjects ≥ 20 years of age on stable lipid-lowering therapy, who received PCSK9 inhibitors during the period 2016 to January 2020. RESULTS: 433 patients (mean age 55 years, 53% male, 39% with cardiovascular disease) were included and followed-up for a median of 2.5 years (IQR 1.6-3.0). Median LDL-C level prior to PCSK9 inhibitors was 145 mg/dL (IQR 125-173). The addition of PCSK9 inhibitors (211 alirocumab, 222 evolocumab) reduced LDL-C by 58% (IQR 41-70) p<0.001, in men and women, achieving a median LDL-C level of 62 mg/dL (IQR 44-87) without differences between both PCSK9 inhibitors. Out of them 67% with and 80% without cardiovascular disease reached 2016 ESC/EAS LDL-C targets, and 46% very high risk and 50% high risk patients achieved 2019 ESC/EAS LDL-C goals. Independent predictor factors for attainment of 2019 ESC/EAS LDL-C goals were to be male, smoking and the use of statins with ezetimibe. Both inhibitors were well tolerated. CONCLUSIONS: PCSK9 inhibitors on top of maximum lipid-lowering treatment significantly reduced LDL-C levels in patients with familial hypercholesterolemia and improved the achievement of LDL-C targets.

In-office endoscopic nasal polypectomy: prospective analysis of patient tolerability and efficacy.

PURPOSE: In-office rhinologic procedures have become popularised in the last decade, especially in North America. Endoscopic nasal polypectomy under local anaesthesia offers instant relief in selected patients with obstructive chronic rhinosinusitis with nasal polyps. We aimed to analyse patient tolerability during the procedure while measuring its effectiveness. METHODS: A prospective study of patients who underwent in-office microdebrider-assisted polypectomy under local anaesthetic from September 2018 to November 2019 in a Spanish tertiary hospital was performed. The tolerability was measured by monitoring vital signs during the procedure and using a visual analogue scale posteriorly. The effectiveness was calculated through patient-reported outcomes (SNOT-22) and endoscopic evaluation 1 and 6 months follow-up. RESULTS: Forty-four patients were included, with a mean age of 60.7 years. The mean visual analogue scale score was 2.76 out of 10 points. Vital signs were steady overall, with a statistically significant reduction (p < 0.001) in systolic pressure during the procedure. Presyncope and epistaxis were among the few mild complications. However, we registered one major complication that required intensive care admission. There was a 64% reduction in the SNOT-22 score in the first month, with a maintained effect after 6 months. Patients with asthma and a higher polyp load were the subgroups that required more time to achieve significant improvement. CONCLUSIONS: In-office polypectomy is a very effective technique that alleviates obstructive symptoms in patients with nasal polyposis, and it is generally safe and well tolerated when performed by an expert. However, rhinologists must be aware of potentially severe complications.

Incidence of cardiovascular events and changes in the estimated risk and treatment of familial hypercholesterolemia: the SAFEHEART registry.

INTRODUCTION AND OBJECTIVES: The SAFEHEART study was designed to analyze the situation of familial heterozygous hypercholesterolemia (FHH) and improve knowledge of this disease in Spain. Our objective was to determine the incidence rate of cardiovascular events, the estimated risk of developing an event and its modification, the use of lipid-lowering treatment, and the achievement of low-density lipoprotein cholesterol targets in patients with FHH. METHODS: SAFEHEART is a prospective, open, multicenter, nationwide cohort study, with long-term protocol-based follow-up in a population of individuals with molecularly-characterized FHH. We analyzed patients older than 18 years with complete follow-up. RESULTS: We included 2648 patients with FHH. The median follow-up was 6.6 (4.8-9.7) years. The overall incidence rate of cardiovascular events was 1.3 events/100 patient-years. After the follow-up, the 10-year estimated risk of developing a cardiovascular event was reduced from 1.6% to 1.3% (P <.001). In the last follow-up, 20.6% and 22.2% of the patients in primary and secondary prevention achieved low-density lipoprotein cholesterol values <100mg/dL and <70mg/dL, respectively. CONCLUSIONS: This study was performed in the largest population of patients with FHH in Spain. We identified the incidence rate of cardiovascular events, the estimated risk of developing a cardiovascular event and its modification, the achievement of low-density lipoprotein cholesterol targets, and the therapeutic management in this population. Although the cardiovascular risk of FHH is high, appropriate treatment reduces the likelihood of an event. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Identifier: NCT02693548.

Subjective benign paroxysmal positional vertigo in patients with osteoporosis or migraine / Vertigem posicional paroxística benigna subjetiva em pacientes com osteoporose ou migrânea

Abstract Introduction Subjective benign paroxysmal positional vertigo is a form of benign paroxysmal positional vertigo in which during the diagnostic positional maneuvers patients only present vertigo symptoms with no nystagmus. Objective To study the characteristics of subjects with subjective benign paroxysmal positional vertigo. Methods Prospective multicenter case-control study. All patients presenting with vertigo in the Dix-Hallpike test that presented to the participating hospitals were included. The patients were separated into two groups depending on whether nystagmus was present or not. An Epley Maneuver of the affected side was performed. In the follow-up visit, patients were checked to see if nystagmus and vertigo were present. Both groups of patients were compared to assess the success rate of the Epley maneuver and also to compare the presence of 19 variables. Results 259 patients were recruited, of which 64 belonged to the subjective group. Nystagmus was eliminated in 67.2% of the patients with benign paroxysmal positional vertigo. 89.1% of the patients with subjective benign paroxysmal positional vertigo remained unaffected by nystagmus, thus showing a significant difference (p = 0.001). Osteoporosis and migraine were the variables which reached the closest to the significance level. In those patients who were taking vestibular suppressors, the percentage of subjective benign paroxysmal positional vertigo was not significantly higher. Conclusions Subjective benign paroxysmal positional vertigo should be treated using the Epley maneuver. More studies are needed to establish a relationship between osteoporosis, migraine and subjective benign paroxysmal positional vertigo. The use of vestibular suppressants does not affect the detection of nystagmus.

Resumo Introdução A vertigem posicional paroxística benigna subjetiva é um tipo de vertigem posicional paroxística benigna na qual, durante as manobras posicionais diagnósticas, os pacientes apresentam apenas sintomas vertiginosos sem nistagmo. Objetivo Estudar as características de indivíduos com vertigem posicional paroxística benigna subjetiva. Método Estudo prospectivo multicêntrico de caso-controle. Foram incluídos todos os pacientes com vertigem no teste de Dix-Hallpike, que se apresentaram nos hospitais participantes. Os pacientes foram separados em dois grupos, dependeu da presença ou não do nistagmo. Uma manobra de Epley foi realizada no lado afetado. Na consulta de seguimento, os pacientes foram avaliados para verificar a presença ou não do nistagmo e da vertigem. Ambos os grupos de pacientes foram comparados para avaliar a taxa de sucesso da manobra de Epley e também para comparar a presença de 19 variáveis. Resultados Foram recrutados 259 pacientes, dos quais 64 pertenciam ao grupo subjetivo. O nistagmo foi eliminado em 67,2% dos pacientes com vertigem posicional paroxística benigna. Em 89,1% dos casos, os pacientes com vertigem posicional paroxística benigna subjetiva mantiveram-se não afetados pelo nistagmo, mostraram uma diferença significativa (p = 0,001). Osteoporose e enxaqueca foram as variáveis que atingiram o nível mais próximo ao de significância. Nos pacientes que tomavam supressores vestibulares, a porcentagem de vertigem posicional paroxística benigna subjetiva não foi significativamente maior. Conclusões A vertigem posicional paroxística benigna subjetiva deve ser tratada com a manobra de Epley. Mais estudos são necessários para estabelecer uma relação entre osteoporose, enxaqueca e vertigem posicional paroxística benigna subjetiva. O uso de supressores vestibulares não afeta a detecção do nistagmo.

Lack of evidence of association between IFNG and IL28B polymorphisms and QuantiFERON-CMV test results in seropositive transplant patients.

The aim of this study was to analyze the relationship between the IFNG +874 T/A and IL28B (rs12979860) C/T polymorphisms and the secretion of IFNG by CD8+ T cells after stimulation with cytomegalovirus (CMV) peptides, measured using QuantiFERON-CMV (QF-CMV) assay. A total of 184 CMV-seropositive solid organ transplant patients (108 kidney, 68 liver and 8 lung) were recruited. Of them, 151 patients were QF-CMV Reactive (IFNG ≥ 0.2 UI/mL) and 33 were Non-reactive. Genotype frequencies in the study population were TT (26.6%), AT (50.0%) and AA (23.4%) for IFNG +874 and CC (52.7%), CT (39.1%) and TT (8.2%) for IL28B (rs12979860). These frequencies did not significantly differ between QF-CMV Reactive and Non-reactive patients. Nor were any significant differences observed in the quantitative IFNG level among the genotypes in either the IFNG or the IL28 genes. When we analyzed whether these polymorphisms had any impact on the risk of CMV replication after transplantation, the adjusted analysis showed no association. In summary, our results showed that IFNG +874 T/A and IL28B (rs12979860) C/T polymorphisms are not associated with the IFNG response to CMV measured by the QuantiFERON-CMV assay, although these results should be confirmed with a higher number of patients.

Regulation of Fn14 Receptor and NF-κB Underlies Inflammation in Meniere's Disease.

Meniere's disease (MD) is a rare disorder characterized by episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a fluid imbalance between the secretion of endolymph in the cochlear duct and its reabsorption into the subarachnoid space, leading to an accumulation of endolymph in the inner ear. Epidemiological evidence, including familial aggregation, indicates a genetic contribution and a consistent association with autoimmune diseases (AD). We conducted a case-control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661-2.627); p = 1.39 × 10-09]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a trans-expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate (p = 2.42 × 10-11). This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-κB. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD.

Coronary Heart Disease, Peripheral Arterial Disease, and Stroke in Familial Hypercholesterolaemia: Insights From the SAFEHEART Registry (Spanish Familial Hypercholesterolaemia Cohort Study).

OBJECTIVE: Heterozygous familial hypercholesterolemia (FH) is the most common premature atherosclerotic cardiovascular disease (ASCVD)-related monogenic disorder, and it is associated with ischemic heart disease. There is limited information whether FH increases the risk of peripheral arterial and cerebrovascular disease. Our aim was to analyze ASCVD prevalence and characteristics in different arterial territories in a large FH population, to compare them with an unaffected control population and to determine which factors are associated to ASCVD. APPROACH AND RESULTS: SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) is an ongoing registry of molecularly defined patients with heterozygous FH in Spain. ASCVD in the different arterial territories was analyzed, as well as individual characteristics, genetic variables, and lipid-lowering therapies. The study recruited 4132 subjects (3745 ≥18 years); 2,752 of those enrolled were molecularly diagnosed FH cases. Median age was 44.0 years (45.9% men) and 40 years (46.6% men) in FH patients and unaffected relatives (P<0.001). ASCVD was present in 358 (13.0%) and 47 (4.7%) FH patients and unaffected relatives, respectively (P<0.001). History of premature ASCVD was more prevalent in FH patients (9.4% and 2.4% in FH patients and unaffected relatives, respectively; P<0.001). Coronary artery-related manifestations and peripheral artery disease were more prevalent in FH patients than in controls, but no significant differences were found for cerebrovascular events. Age, body mass index, type 2 diabetes mellitus, high blood pressure, previous use of tobacco, and lipoprotein(a) >50 mg/dL were independently associated with ASCVD. CONCLUSIONS: The prevalence of ASCVD is higher, and the involvement of the arterial territories is different in FH patients when compared with their unaffected relatives. Age, male sex, increased body mass index, hypertension, type 2 diabetes mellitus, smoking habit, and lipoprotein(a) >50 mg/dL were independently associated to ASCVD. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02693548.

NUMB inactivation confers resistance to imatinib in chronic myeloid leukemia cells.

Chronic myeloid leukemia (CML) progresses from a chronic to a blastic phase, where the leukemic cells are proliferative and undifferentiated. The CML is nowadays successfully treated with BCR-ABL kinase inhibitors as imatinib and its derivatives. NUMB is an evolutionary well-conserved protein initially described as a functional antagonist of NOTCH function. NUMB is an endocytic protein associated with receptor internalization, involved in multiple cellular functions. It has been reported that MSI2 protein, a NUMB inhibitor, is upregulated in CML blast crisis, whereas NUMB itself is downregulated. This suggest that NUMB plays a role in the malignant progression of CML. Here we have generated K562 cells (derived from CML in blast crisis) constitutively expressing a dominant negative form of NUMB (dnNUMB). We show that dnNUMB expression confers a high proliferative phenotype to the cells. Importantly, dnNUMB triggers a partial resistance to imatinib in these cells, antagonizing the apoptosis mediated by the drug. Interestingly, imatinib resistance is not linked to p53 status or NOTCH signaling, as K562 lack p53 and imatinib resistance is reproduced in the presence of NOTCH inhibitors. Taken together, our data support the hypothesis that NUMB activation could be a new therapeutic target in CML.

Statins do not increase the risk of developing type 2 diabetes in familial hypercholesterolemia: The SAFEHEART study.

BACKGROUND: Familial Hypercholesterolemia (FH) is the most common monogenic disorder that causes premature coronary artery disease (CAD). Our objective was to examine the risk of new onset type 2 diabetes mellitus (T2DM) among FH patients and unaffected relatives in relation to treatment with different statins in the SAFEHEART cohort study. METHODS: This is a cross-sectional and prospective cohort study in 2558 FH and 1265 unaffected relatives with a mean follow-up of 5.9 years. Several pertinent data, such as age, gender, metabolic syndrome, lipid profile, body mass index (BMI), waist circumference, HOMA-IR, dose, duration and type of statins, were obtained and examined as predictors of incident diabetes. RESULTS: The new onset diabetes was 1.7% in FH and 0.2% in non FH patients (p=0.001). In multivariate logistic regression, age (OR 1.02, CI 95%: 1.02-1.08), HOMA-IR (OR 1.17, CI 95%: 1.03-1.33), metabolic syndrome (OR 3.3, CI 95%: 1.32-8.28) and specifically plasma glucose, as a component of metabolic syndrome (OR 15.7, CI 95%: 4.70-52.53) were significant predictors of new onset T2DM in the FH group alone. In the adjusted Cox regression model in FH group, age (HR 1.03, CI 95% 1.00-1.06, p=0.031) and metabolic syndrome (HR 4.16, CI 95% 1.58-10.92, p=0.004) remained significant predictors of new onset T2DM. CONCLUSIONS: Our data do not support the postulated diabetogenic effect associated with high-dose statins use in our cohort of FH patients.

Antiadenohypophysis autoantibodies in patients with nongluten-related gastroenteropathies.

AIM: To investigate the presence of antipituitary antibodies (APA) in the serum of patients undergoing gastroenteropathies (GEP) other than celiac disease (CD). METHODS: APA were analyzed in GEP patients (n = 103), CD patients (n = 94), idiopathic growth hormone (GH) deficiency patients (n = 21), and 98 age- and sex-matched controls. Indirect immunofluorescence was performed in cryostat sections of baboon pituitary gland. RESULTS: APA were detected in 30% of GEP patients, 38% of them showed failure to thrive. No significant differences were found when we compared thrive impairment in negative and positive APA GEP patients. Indeed, normal values of insulin-like growth factor 1 were found in 93% of positive APA GEP patients. APA were detected in 52% of the CD patients. Ninety-one percent of them, in contrast to GEP group, showed significant growth impairment (P < 0.05) when compared to APA negative CD individuals. GH-deficient non-CD patients did not show APA. CONCLUSIONS: We have shown the presence of APA in patients with nongluten-related enteropathies. The presence of antipituitary autoantibodies in GEP patients does not seem to be associated with failure to thrive as it occurs in CD.

Interleukin-21 overexpression dominates T cell response to Epstein-Barr virus in a fatal case of X-linked lymphoproliferative syndrome type 1.

Interleukin-21 (IL-21) is a cytokine whose actions are closely related to B cell differentiation into plasma cells as well as to CD8(+) cytolytic T cell effector and memory generation, influencing the T lymphocyte response to different viruses. X-linked lymphoproliferative syndrome type 1 (XLP-1) is a primary immunodeficiency syndrome that is characterized by a high susceptibility to Epstein-Barr virus. We observed in a pediatric patient with XLP-1 that IL-21 was expressed in nearly all peripheral blood CD4(+) and CD8(+) T cells. However, IL-21 could not be found in the lymph nodes, suggesting massive mobilization of activated cells toward the infection's target organs, where IL-21-producing cells were detected, resulting in large areas of tissue damage.

A novel phenotype variant of severe congenital neutropenia caused by G6PC3 deficiency.

Severe congenital neutropenia type 4 (SCN4) is associated with mutations in the G6PC3 gene. To date, all patients bearing the p.Gly260Arg variant of the G6PC3 gene show heart defects. Here, we present a case of the p.Gly260Arg variant in a patient who did not have structural or functional heart anomalies. Treatment with granulocyte colony-stimulating factor recovered the absolute neutrophil count and neutrophil functional competence.

[Bilateral cochlear implants in children: acquisition of binaural hearing]. / Implantes cocleares bilaterales en la población infantil: adquisición de la binauralidad.

INTRODUCTION AND OBJECTIVES: Several studies have indicated the benefit of bilateral cochlear implants in the acquisition of binaural hearing and bilateralism. In children with cochlear implants, is it possible to achieve binaurality after a second implant? When is the ideal time to implant them? The objective of this study was to analyse the binaural effect in children with bilateral implants and the differences between subjects with simultaneous and sequential implants with both short and long intervals. PATIENTS AND METHODS: There were 90 patients between 1 and 2 years of age (the first surgery), implanted between 2000 and 2008. Of these, 25 were unilateral users and 65 bilateral; 17 patients had received simultaneous implants, 29 had sequential implants before 12 months after the first one (short interimplant period) and 19 after 12 months (long period). All of them were tested for silent and noisy verbal perception and a tonal threshold audiometry was performed. RESULTS: The silent perception test showed that the simultaneous and short period sequential implant patients (mean: 84.67%) versus unilateral and long period sequential implants (mean: 79.66%), had a statistically-significant difference (P=0,23). Likewise, the noisy perception test showed a difference with statistical significance (P=0,22) comparing the simultaneous implanted and short period sequential implants (mean, 77.17%) versus unilateral implanted and long period sequential ones (mean: 69.32%). CONCLUSIONS: The simultaneous and sequential short period implants acquired the advantages of binaural hearing.