Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study

Abstract Objective: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. Method: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. Results: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4% (p = 0.006). Conclusion: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Aspectos a considerar para el diagnóstico del queratocono infantil / Aspects to consider for the diagnosis of infant keratoconus

Introducción: Globalmente, existe un aumento de la prevalencia del queratocono y su diagnóstico en edades tempranas. Se notifican un gran número de casos subclínicos y otros con una rápida progresión, condicionada por el inicio precoz de la enfermedad y la asociación a factores de riesgo. Objetivo: Describir los aspectos epidemiológicos, clínicos y el resultado de los medios de diagnóstico implicados en la detección precoz del queratocono infantil. Desarrollo: En niños con ametropía hay elementos que alertan la presencia de un queratocono como causa del defecto refractivo. Desde el punto de vista epidemiológico se encuentran: distribución geográfica, rol de la herencia y factores ambientales. Clínicamente se señalan los antecedentes de enfermedades, tales como las alergias, la presencia de miopía o astigmatismo miópico con inestabilidad refractiva y los signos clínicos relacionados con la progresión del cono. En los pacientes de riesgo es preciso realizar exámenes mediante diferentes medios de diagnóstico según su disponibilidad, siendo primordial el análisis refractivo, queratométrico y topográfico. Conclusiones: En la evaluación de los niños con ametropía se deben tener en cuenta elementos epidemiológicos y clínicos que permiten sospechar y diagnosticar precozmente el queratocono. En la interpretación de los resultados de los medios de diagnóstico involucrados en su detección, se deben considerar los hallazgos más frecuentes en la población infantil según el grado de progresión de la ectasia.

Introduction: Globally, there is an increase of the keratoconus prevalence and its diagnosis in early ages. A great number of subclinical cases and others with a quick progression are notified, conditioned by the early onset of the disease and the association with risk factors. Objective: To describe the epidemiological, clinical aspects and the result of diagnostic means involved in the early detection of infant keratoconus. Development: There are elements that alert the presence of a keratoconus as a cause of the refractive defect in children with ametropia. From the epidemiologic point of view they are: geographical distribution, heredity role and environmental factors. History of previous diseases are clinically pointed out, such as allergies, myopia or myopic astigmatism with refractive instability and the clinical signs related to cone progression. In risk patients it is necessary to carry out exams by means of different diagnostic means according to their availability, being essential the refractive, keratometric and topographic analysis. Conclusions: In the evaluation of children with ametropia, epidemiological and clinical elements should be taken into account that allow to suspect and early diagnose the keratoconus. In the interpretation of results of the diagnostic means involved in their detection the most frequent findings in the infant population, should be considered according to the ectasia degree of progression.

Application of FMEA model and 6S management method in reducing dispensing errors in PIVAS of children’s hospitals / 中国药房

OBJECTIVE To reduce dispensing errors in pharmacy intravenous admixture service （PIVAS） of children’s hospitals. METHODS The risk of dispensing procedures in our PIVAS was identified by applying failure mode and effect analysis （FMEA） model. Potential failure modes that might lead to dispensing errors in each link were determined， and failure causes were analyzed. The severity， incidence and detection degree of potential failure modes were quantitatively scored， and their risk priority number （RPN） was calculated to screen failure modes that needed to be improved in priority； the corresponding improvement measures were developed by 6S management method from six aspects， namely， finishing （seiri）， rectifying （seiton）， sweeping （seiso）， sanitation （seiketsu）， literacy （shitsuke） and safety. The effect of intervention before and after rectification was evaluated. RESULTS Based on the RPN， 32 potential failure modes were selected， of which a total of 18 critical failure modes that needed to be improved in priority. After implementing corresponding measures according to 6S management method， the RPN of 18 critical failure modes decreased. The total RPN decreased from 497 to 142 with a decrease rate of 71.43%. The error rates of 15 critical failure modes were significantly lower than before implementation （P＜0.05）. CONCLUSIONS Applying FMEA model and 6S management method to the risk control of all aspects of PIVAS workflow can effectively reduce the risk of PIVAS dispensing errors and ensure the safety of children’s intravenous medication.

Errors and countermeasures of robotic surgery system in thyroid surgery application / 国际外科学杂志

The purpose of minimally invasive thyroid surgery is to perform refined surgery through an intelligent operating system, achieving minimal physical and psychological trauma for patients, thereby improving their quality of life. At present, the commonly used minimally invasive surgical methods are laparoscopic surgery and robotic surgery, both by creating tunnels from a distance to the thyroid gland, requiring high technical requirements for surgical instruments and robotic surgeons. Regardless of the type of minimally invasive surgery, in the early stages of implementation, doctors have a process of exposure, understanding, proficient mastery, and innovative expansion of the system, instruments, operating methods, and surgical thinking. In this process, it is inevitable to encounter some erroneous operations, which are the main causes of medical safety adverse events, including complications, and bring a failed medical experience to patients. At the same time, mistakes can also cause psychological burden for robotic surgeons and have an impact on the development of new technologies. The occurrence of errors also depends on the open surgical experience and clinical adaptability of robotic surgeons, and experienced robotic surgeons can significantly reduce errors. With the innovation of medical technology and the urgent demand of patients for efficacy and beauty, errors should not be a factor hindering the development of minimally invasive thyroid surgery. This article will analyze the erroneous operations of robot surgeons, formulates countermeasures, and provides reference for the safe implementation of robot surgery, thereby promoting the development of intelligent precision minimally invasive surgery, and further benefiting patients with minimally invasive needs.

Peripheral immune profile and gene variations of 11 immunodeficiency virus-negative children with Talaromyces marneffei infection / 中华实用儿科临床杂志

Objective:To explore the immunological characteristics of peripheral blood and genetic variations of 11 immunodeficiency virus(HIV)-negative children with Talaromyces marneffei(TM) infection, thus enhancing the diagnostic and therapeutic levels of TM infection in children. Methods:Clinical data of 11 HIV-negative children with TM infection who presented to Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from January 2010 to December 2022 were retrospectively analyzed, including clinical characteristics, peripheral immune profile and genetic test results.Results:A total of 11 HIV-negative children with TM infections were recruited, involving 9 males and 2 females with a median age of 19 months.The main clinical manifestations were fever (10/11, 90.91%), cough (10/11, 90.91%) and hepatomegaly (7/11, 63.64%). Common severe complications included acute respiratory distress syndrome (7/11, 63.64%) and septic shock (5/11, 45.45%). Finally, 2 children died.Transient neutropenia occurred in 6 cases (6/11, 54.55%), and lymphocytopenia combined with serum immunoglobulin (Ig) G decrease was observed in 4 cases (4/11, 36.36%). IgA decrease, IgM decrease, IgE decrease, IgM increase and IgE increase were observed in 6 cases, 3 cases, 5 cases, 3 cases, and 2 cases, respectively.Both T-lymphocyte and B-lymphocyte counts decreases was observed in 1 case.Genetic testing was performed in all recruited children, and genetic variations were detected in all of them.Inborn errors of immunity (IEIs) were diagnosed in 8 cases, including 4 diagnosed as CD 40 ligand deficiency with CD40LG variation, 1 of severe combined immunodeficiency with IL2RG variation, 1 of Signal transduction and activator of transcription 3(STAT3)-hyper-IgE syndrome with STAT3 variation and 1 of familial candidiasis type 2 with CARD9 compound heterozygous mutations.In the other 3 cases, 2 carried genetic variations that were likely pathogenic, and 1 case was considered uncertain. Conclusions:The clinical manifestations of HIV-negative children with TM infection are atypical, which is characterized as serious complications and high mortality.Early identification and gene testing to detect potential IEIs can improve the prognosis of TM infection.

Continuous renal replacement therapy for neonatal hyperammonemia: 10 cases experience / 中国新生儿科杂志

Objective:To study clinical outcomes, genetic etiology, efficacy and safety of continuous renal replacement therapy (CRRT) for neonatal hyperammonemia.Methods:From September 2016 to June 2023, neonates with hyperammonemia receiving CRRT in NICU of our hospital were retrospectively analyzed. Their perinatal conditions, clinical manifestations, laboratory results, genetic tests, treatments and outcomes were collected. The patients were assigned into survival group and death group according to their conditions at discharge. SPSS 22.0 statistical software was used to analyze the differences between the two groups.Results:A total of 10 patients were enrolled, including 8 males and 2 females. The gestational age was 39.3(38.2,39.8)weeks and birth weight 3 300(3 050, 3 583) g. The age of onset was 2.0(2.0, 4.3) d. The main clinical manifestations included seizures, coma and high blood ammonia level (up to 586-1 250 μmol/L). The patients received CRRT at 3.0(2.0, 8.3) d of age and CRRT lasted for 20.5(16.5, 42.8) h. Before CRRT, average time of coma was 10.0(3.5, 12.8) h and the total duration of coma was 20.5(12.5, 29.0) h. After CRRT, blood ammonia decreased (52.6±22.2) μmol/L every hour for 6 h. The genetic tests showed ornithine transcarbamylase deficiency in 5 cases, methylmalonic acidemia in 2 cases, propionic acidemia in 1 case, carnitine acylcarnitine translocase deficiency in 1 case and transient hyperammonemia in 1 case. 6 patients survived. 4 patients died at discharge, including 2 withdrawal treatment. The duration of coma before CRRT and the total duration of coma in the death group were significantly longer than the survival group ( P<0.05). Conclusions:Inborn metabolic error are common causes of neonatal hyperammonemia. Timely CRRT can safely and effectively reduce blood ammonia levels and may improve clinical outcomes.

Bibliometric analysis of scleral lens research trends based on Web of Science / 中华实验眼科杂志

Objective:To analyze the research status of scleral lenses by bibliometric method based on the relevant collection of scleral lenses in the Web of Science database.Methods:Using the scleral lens-related literature collected in the Web of Science Core Collection database in the past 10 years (January 2013 to December 2022) as the object of analysis, bibliometric method and CiteSpace tools were used to conduct visual analysis of the literature.A comprehensive analysis of the volume of literature published, the distribution of countries and institutions, the information of core authors, the distribution of journals, and keyword clustering was performed.Results:A total of 340 articles were retrieved, which were published in 54 journals, with an average of 6.3 articles per journal, involving 301 authors.Research in this area covered 35 countries or regions, and 256 research institutions were involved.Discipline development was mainly in the United States, India, Spain and Australia.The main focus was on scleral lens (scleral contact lens), ocular surface disease, corneal edema, miniature scleral lens, etc.In the past 10 years, the trend of research hot topics in scleral lenses had shifted from the initial study of combining scleral contact lenses with ocular surface diseases to the subsequent study of prosthetic replacement of the ocular surface ecosystem, and the exploration of corneal clearance and shape.From 2013 to 2021, the main focuses were ocular surface diseases, scleral contact lenses, and corneal edema.After 2021, research on ocular surface diseases and keratoplasty declined.From January 2013 to December 2022, emergent keywords related to scleral lens mainly included scleral contact lens, transplantation, anti-host disease, prosthetic device in the first stage, artificial replacement of ocular surface ecosystem and irregular cornea in the second stage, and the research on corneal gap and characteristic shape in the third stage.Optical coherence tomography and corneal topography were commonly used examinations for scleral lens research and fitting.Conclusions:At present, the scleral lens is mainly used for dry eye, corneal diseases, corneal ectasia, keratitis, and corneal transplantation, especially after penetrating keratoplasty and refractive errors.Prosthetic replacement of the ocular surface ecosystem, and the exploration of corneal clearance and shape are the research hotspots in scleral lenses.

Efficacy and safety of refractive surgery combined with prophylactic collagen cross-linking for ametropia / 中华实验眼科杂志

Corneal refractive surgery is a safe and effective way to correct ametropia.Although the biomechanical stability of the cornea is reduced due to the change in corneal tissue integrity after surgery, the vast majority of postoperative corneal structures are safe.Patients with preoperative risk factors, such as high diopters, thin cornea, irregular corneal topography, high astigmatism, binocular asymmetry, allergic constitution, eye rubbing, etc., may experience postoperative refractive regression and corneal ectasia.Corneal collagen cross-linking can enhance the biomechanical properties of cornea and effectively prevent the occurrence and progression of corneal ectasia, keratoconus or other ectatic diseases.In recent years, many researchers at home and abroad have tried a new design of refractive surgery, that is, corneal refractive surgery with prophylactic corneal collagen cross-linking to improve the biomechanical stability of the cornea after refractive surgery, and then potentially prevent corneal ectasia and refractive regression.A number of studies have found that combined surgery has a good visual acuity and refractive prognosis, especially in patients at high risk for postoperative ectasia.This article reviews the efficacy, safety, predictability, stability, and complications of combined surgery.

An interpretation of the new version of Refractive Errors Preferred Practice Pattern? / 中华实验眼科杂志

In September 2022, the American Academy of Ophthalmology released the latest version of Refractive Errors Preferred Practice Pattern? (PPP). It provides authoritative guidance for the diagnosis and treatment of refractive errors based on the best evidence-based medical updates.The new version of Refractive Errors PPP continues the rigorous, comprehensive and detailed features of the 2017 version.Updates have been made to the definition, epidemiology, classification, and diagnosis and correction of refractive errors.For example, the new version of Refractive Errors PPP defines high refractive errors as myopia≥-6.0 D, hyperopia≥+ 3.0 D, astigmatism≥-3.0 D, adds content on myopia prevention and control, recommends outdoor activities for at least 2 hours per day, selects appropriate optical prevention and control methods, and considers the use of low-concentration atropine eye drops to delay the onset and development of myopia.It enriched the evidence-based medical evidence that myopia is an interactive influence of genetic and environmental factors, and emphasized the future pandemic trend of high myopia, and the global public health significance of delaying the progression of myopia.In addition, the new version of Refractive Errors PPP emphasizes for the first time that myopia can cause irreversible visual impairment, suggesting that it is necessary to delay the onset time of myopia in children and slow the speed of myopia progression.This article introduces and interprets the main contents and updates of the new edition of the Refractive Errors PPP.

Features of dominant eye and the significance of ocular dominance switching in the treatment of ocular diseases / 中华实验眼科杂志

The dominant eye is the eye that plays a significant role in visual perception.It plays an essential role in binocular vision and fusion functions with a complex formation mechanism.According to the principle of the dominant eye examination method, ocular dominance can be classified into sighting, motor, and sensory dominance.Changes in visual acuity or visual function due to the unbalanced progression of binocular disease may lead to the switch in the dominant eye, affecting the balance of binocular vision and the therapeutic effect.Therefore, misjudging or neglecting of the dominant eye will change the long-term visual balance between the eyes, which may affect people's visual quality and quality of life.These aspects are mainly represented in the process of refractive error correction, refractive surgery, strabismus correction surgery, amblyopia training methods and cataract intraocular lens measurement.The formulation of medical plans based on the strategy of the dominant eye can remarkably improve the reconstruction good binocular vision and the quality of life of patients.However, the role of the dominant eye in binocular vision is not fully understood, and clinicians are not sufficiently aware of its importance.Therefore, this study will review the latest research progress on the mechanism of dominant eye formation, examination methods, and clinical significance of dominant eye switching.