HLH as an additional warning sign of inborn errors of immunity beyond familial-HLH in children: a systematic review.

Background: Hemophagocytic Lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by a severe impairment of the immune homeostasis. While Familial-HLH (FHL) is a known cause, the involvement of other Inborn Errors of Immunity (IEI) in pediatric-HLH remains understudied. Objective: This systematic review aimed to assess the clinical features, triggers, laboratory data, treatment, and outcomes of pediatric HLH patients with IEI other than FHL (IEInotFHL), emphasizing the importance of accurate identification and management. Methods: A systematic search for studies meeting inclusion criteria was conducted in PubMed, EMBASE, MEDLINE, and Cochrane Central. Quality assessment was performed through JBI criteria. Results: A comprehensive search yielded 108 records meeting inclusion criteria, involving 178 patients. We identified 46 different IEI according to IUIS 2022 Classification. Combined immunodeficiencies, immune dysregulation disorders, and phagocyte defects were the IEI most frequently associated with HLH. In 75% of cases, HLH preceded the IEI diagnosis, often with an unrecognized history of severe infections. Triggers reflected the specific infection susceptibilities within IEI groups. Liver and central nervous system involvement were less common than in FHL cases. Treatment approaches and outcomes varied, with limited long-term follow-up data, limiting the assessment of therapeutic efficacy across IEI groups. Conclusion: A comprehensive evaluation encompassing immunological, infectious, and genetic aspects is essential in pediatric-HLH. Relying solely on FHL or EBV susceptibility disorders tests is insufficient, as diverse other IEI can contribute to HLH. Early recognition of HLH as a potential warning sign can guide timely diagnostic investigations and facilitate tailored therapeutic interventions for improved outcomes. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371425, PROSPERO, CRD42022371425.

Inside the Noonan "universe": Literature review on growth, GH/IGF axis and rhGH treatment: Facts and concerns.

Noonan syndrome (NS) is a disorder characterized by a typical facial gestalt, congenital heart defects, variable cognitive deficits, skeletal defects, and short stature. NS is caused by germline pathogenic variants in genes coding proteins with a role in the RAS/mitogen-activated protein kinase signaling pathway, and it is typically associated with substantial genetic and clinical complexity and variability. Short stature is a cardinal feature in NS, with evidence indicating that growth hormone (GH) deficiency, partial GH insensitivity, and altered response to insulin-like growth factor I (IGF-1) are contributing events for growth failure in these patients. Decreased IGF-I, together with low/normal responses to GH pharmacological provocation tests, indicating a variable presence of GH deficiency/resistance, in particular in subjects with pathogenic PTPN11 variants, are frequently reported. Nonetheless, short- and long-term studies have demonstrated a consistent and significant increase in height velocity (HV) in NS children and adolescents treated with recombinant human GH (rhGH). While the overall experience with rhGH treatment in NS patients with short stature is reassuring, it is difficult to systematically compare published data due to heterogeneous protocols, potential enrolment bias, the small size of cohorts in many studies, different cohort selection criteria and varying durations of therapy. Furthermore, in most studies, the genetic information is lacking. NS is associated with a higher risk of benign and malignant proliferative disorders and hypertrophic cardiomyopathy, and rhGH treatment may further increase risk in these patients, especially as dosages vary widely. Herein we provide an updated review of aspects related to growth, altered function of the GH/IGF axis and cell response to GH/IGF stimulation, rhGH treatment and its possible adverse events. Given the clinical variability and genetic heterogeneity of NS, treatment with rhGH should be personalized and a conservative approach with judicious surveillance is recommended. Depending on the genotype, an individualized follow-up and close monitoring during rhGH treatments, also focusing on screening for neoplasms, should be considered.

Psychosocial assessment of families caring for a child with acute lymphoblastic leukemia, epilepsy or asthma: Psychosocial risk as network of interacting symptoms.

The purpose of this study is to assess psychosocial risk across several pediatric medical conditions and test the hypothesis that different severe or chronic pediatric illnesses are characterized by disease specific enhanced psychosocial risk and that risk is driven by disease specific connectivity and interdependencies among various domains of psychosocial function using the Psychosocial Assessment Tool (PAT). In a multicenter prospective cohort study of 195 patients, aged 5-12, 90 diagnosed with acute lymphoblastic leukemia (ALL), 42 with epilepsy and 63 with asthma, parents completed the PAT2.0 or the PAT2.0 generic version. Multivariate analysis was performed with disease as factor and age as covariate. Graph theory and network analysis was employed to study the connectivity and interdependencies among subscales of the PAT while data-driven cluster analysis was used to test whether common patterns of risk exist among the various diseases. Using a network modelling approach analysis, we observed unique patterns of interconnected domains of psychosocial factors. Each pathology was characterized by different interdependencies among the most central and most connected domains. Furthermore, data-driven cluster analysis resulted in two clusters: patients with ALL (89%) mostly belonged to cluster 1, while patients with epilepsy and asthma belonged primarily to cluster 2 (83% and 82% respectively). In sum, implementing a network approach improves our comprehension concerning the character of the problems central to the development of psychosocial difficulties. Therapy directed at problems related to the most central domain(s) constitutes the more rational one because such an approach will inevitably carry over to other domains that depend on the more central function.

Correlation between inner retinal layer thickness and cognitive function in HIV: new insights from an exploratory study.

OBJECTIVE: To compare retinal layer thickness in HIV-infected subjects with (CI-HIV) and without (NCI-HIV) cognitive impairment, with a control population and to correlate this with the cognitive status of the patient and other clinical parameters. DESIGN: Single-center cross-sectional study. METHODS: Participants with controlled HIV infection aged between 40 and 70 years and sex-matched and age-matched controls were enrolled. Retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) and inner plexiform layer (IPL) thickness were assessed using optical coherence tomography. These measurements in HIV patients were compared with those in controls. Age-related and sex-related changes were compared in both groups. Other variables studied in HIV patients included: duration of HIV infection, CD4 cell count nadir, antiretroviral therapy regimen and cognitive status using the Montreal Cognitive Assessment (MoCA) test. RESULTS: Sixty-nine individuals, 34 with and 35 without cognitive impairment, and 70 controls were enrolled. GCL was significantly thinner in CI-HIV patients compared with NCI-HIV patients and controls (P = 0.01 and P = 0.02, respectively). GCL and IPL thickness significantly decreased with age in patients with HIV (P = 0.0003, P = 0.02, respectively, for the entire cohort). This change was not seen in controls. MoCA test score significantly decreased with age in HIV patients and controls. GCL thickness positively correlated with cognitive function across the entire HIV cohort (P = 0.02). CONCLUSION: GCL was thinner in HIV patients with cognitive impairment. GCL thickness correlated positively with cognitive function and negatively with age in HIV patients. GCL thickness may reflect accelerated cognitive aging in HIV.

IL-13 and idiopathic pulmonary fibrosis: Possible links and new therapeutic strategies.

The recent advances in the knowledge of immunological aspects of many pulmonary diseases, allowed to identify cells, biological functions, cytokines, and receptors that are preferentially involved in each disease. This is the case of asthma, where IL-13 (together with IL-4) is recognized as a central mediator. The role of IL-13 is strictly related, via complex signaling pathways, to eosinophil recruitment and activation, to mucus secretion, periostin generation and to fibrogenic processes (which are part of the remodeling process). These peculiar roles of IL-13 have suggested the hypothesis of its role in Idiopathic Pulmonary Fibrosis, and consequently of its antagonists in the treatment of such disease. We review herein the immunological roles of IL-13 in asthma and IPF, and the currently ongoing attempts to treat IPF by IL-13 antagonism strategies.

Asthma management in a specialist setting: Results of an Italian Respiratory Society survey.

BACKGROUND: Asthma considerably impairs patients' quality of life and increases healthcare costs. Severity, morbidity, and degree of disease control are the major drivers of its clinical and economic impact. National scientific societies are required to monitor the application of international guidelines and to adopt strategies to improve disease control and better allocate resources. AIM: to provide a detailed picture of the characteristics of asthma patients and modalities of asthma management by specialists in Italy and to develop recommendations for the daily management of asthma in a specialist setting. METHOD: A quantitative research program was implemented. Data were collected using an ad hoc questionnaire developed by a group of specialists selected by the Italian Pneumology Society/Italian Respiratory Society. RESULTS: The records of 557 patients were analyzed. In the next few years, specialists are expected to focus their activity patients with more severe disease and will be responsible for selection of patients for personalized biological therapy; however, only 20% of patients attending Italian specialist surgery can be considered severe. In 84.4% of cases, the visit was a follow-up visit requested in 82.2% of cases by the specialist him/herself. The Asthma Control Test is used only in 65% of patients. When available, a significant association has been observed between the test score and asthma control as judged by the physician, although concordance was only moderate (κ = 0.68). Asthma was considered uncontrolled by the specialist managing the case in 29.1% of patients; nevertheless, treatment was not stepped up in uncontrolled or partly controlled patients (modified in only 37.2% of patients). CONCLUSIONS: The results of this survey support re-evaluation of asthma management by Italian specialists. More resources should be made available for the initial visit and for more severely ill patients. In addition, more extensive use should be made of validated tools, and available drugs should be used more appropriately.

Melanoma maligno en cavidad bucal en una mujer de Tucumán, Argentina / Malignant melanoma of the oral cavity in a woman from Tucuman, Argentina

El melanoma es un cáncer de origen melanocítico extremadamente raro, de pronóstico grave con una pobre sobrevida a los cinco años. El objetivo del presente trabajo es comunicar un caso clínico de melanoma de la cavidad bucal correspondiente a una mujer de 75 años de edad, en la cuál se estudiaron los niveles séricos de las enzimas lisosomales, Fosfatasa Ácida (FA), Hexosaminidasa (Hex), Beta Galactosidasa ( -Gal) y el Antígeno Carcinoembrionario (CEA). El tratamiento efectuado fue quirúrgico completándose el mismo con quimio e inmunoterapia, falleciendo la paciente a los doce meses del diagnóstico. El dosaje de las enzimas lisosomales séricas al momento del diagnóstico mostraban un valor superior al valor máximo normal, por lo que investigaciones posteriores podrían validar el dosaje de estas enzimas como método complementario para el diagnóstico de esta patología. La identificación de lesiones precursoras del melanoma maligno y la determinación de marcadores tumorales séricos junto a la aplicación de terapias locales y sistémicas mas efectivas podrían contribuir a mejorar la sobrevida de estos pacientes.

The melanoma is a melanocytic start cancer extremely strange, of serious forecast with a poor survive at five year. The aim of the present work is communicate a clinical case of mouth cavity melanoma belonging to a 75-year-old woman, in which were studied lysosomal enzymes levels, Acid Fosfatase (FA), Hexosaminidase (Hex), B-Galactosidasa (B-Gal) and the Carcinoembrionic Antigen (CEA). The treatment carried out was surgical and being completed with quimio and immunotherapy, dying twelve months latter the patient. The seric lysosomal enzymes at the moment of diagnostic showed a value over the normal one, for what this study suggested may be used as complementary method of diagnosis to this pathology. The precursor injuries identification of malignant melanoma and seric determination of tumour scoreboards with the application of local and systemic therapies more effective might help to provide better survive to these patients.

Influência da lista única de uma regional de transplantes de córnea em um Banco de Olhos vinculado a um hospital escola / Influence of a single regional list for corneal transplantation on the eye bank of a university hospital

OBJETIVO: Avaliar como a implantação do sistema de lista única para transplantes de córnea influenciou um Banco de Olhos vinculado a um hospital escola. Analisar sua interferência nas córneas (captação e destino), no número de transplantes realizados e também na média de tempo de espera pela cirurgia. MÉTODOS: Foi realizado estudo retrospectivo, avaliando os prontuários dos pacientes submetidos a ceratoplastia penetrante e também os dados do Banco de Olhos da Faculdade de Medicina de São José do Rio Preto - SP. O estudo comparou dados relativos ao funcionamento do serviço por um ano antes e após a criação da lista única. RESULTADOS: O número de cirurgias aumentou de 60 para 92 cirurgias. A média mensal de córneas retiradas aumentou de 13,83 ± 6,57 para 18,16 ± 4,80 (p=0,07). O número de córneas enviadas por esta instituição foi maior que o número de córneas recebidas de outros serviços (p=0,003). Não houve diferença significativa entre o tempo de espera pela cirurgia antes e após a criação da fila única (desconsiderando o período de cadastramento). CONCLUSÕES: Este Banco de Olhos funcionou como fornecedor de córneas para outras instituições. Após seu primeiro ano de funcionamento, a implantação da lista única não alterou o tempo de espera dos pacientes pela cirurgia. Apesar disso, evidenciou-se uma tendência à homogeneização do tempo de espera pela ceratoplastia penetrante entre os pacientes.