- Changing respiratory expectations with the new disease trajectory of nusinersen treated spinal muscular atrophy [SMA] type 1. [Review]
- PRPaediatr Respir Rev 2018 Jul 12
- Spinal muscular atrophy [SMA] is the most common genetic cause of childhood mortality, primarily from the most severe form SMA type 1. It is a severe, progressive motor neurone disease, affecting the...
Spinal muscular atrophy [SMA] is the most common genetic cause of childhood mortality, primarily from the most severe form SMA type 1. It is a severe, progressive motor neurone disease, affecting the lower brainstem nuclei and the spinal cord. There is a graded level of severity with SMA children from a practical viewpoint described as "Non-sitters", "Sitters" and less commonly, "Ambulant" correlating with SMA Type 0/Type 1, Type 2 and Type 3 respectively. Children with SMA Type 0 have a severe neonatal form whilst those with SMA Type 1 develop hypoventilation, pulmonary aspiration, recurrent lower respiratory tract infections, dysphagia and failure to thrive before usually succumbing to respiratory failure and death before the age of 2 years. The recent introduction of the antisense oligonucleotide nusinersen into clinical practice in certain countries, following limited trials of less than two years duration, has altered the treatment landscape and improved the outlook considerably for SMN1 related SMA. Approximately 70% of infants appear to have a clinically significant response to nusinersen with improved motor function. It appears the earlier the treatment is initiated the better the response. There are other rarer genetic forms of SMA that are not treated with nusinersen. Clinical expectations will change although it is unclear as yet what the extent of response will mean in terms of screening initiatives [e.g., newborn screening], "preventative strategies" to maintain respiratory wellbeing, timing of introduction of respiratory supports, and prolonged life expectancy for the subcategory of children with treated SMA type 1. This article provides a review of the strategies available for supporting children with respiratory complications of SMA, with a particular emphasis on SMA Type 1.
- An X-Linked Hyper-IgM Patient Followed Successfully for 23 Years without Hematopoietic Stem Cell Transplantation. [Journal Article]
- CRCase Reports Immunol 2018; 2018:6897935
- When caring for patients with life-limiting diseases, improving survival and optimizing quality of life are the primary goals. For patients with X-linked hyper-IgM syndrome (XHIGM), the treatment mod...
When caring for patients with life-limiting diseases, improving survival and optimizing quality of life are the primary goals. For patients with X-linked hyper-IgM syndrome (XHIGM), the treatment modality has to be decided for a particular patient regarding hematopoietic stem cell transplantation or intravenous immunoglobulin replacement therapy with P. jiroveci prophylaxis. A seven-year-old male patient was admitted with recurrent upper and lower respiratory tract infections and recurrent otitis media. His initial immunologic evaluation revealed low IgG and normal IgA and IgM levels with normal lymphocyte phenotyping and inadequate specific antibody responses. He was diagnosed as common variable immunodeficiency and began to receive intravenous immunoglobulin (IVIG) (0.5 gm/kg) with four-week intervals. During follow-up for 23 years under IVIG therapy, he was extremely well and never had severe infections. In 2017, targeted next generation sequencing was performed in order to understand his molecular pathology. A previously described hemizygous c.31C>T(p.Arg11Ter) mutation was found in CD40LG gene. The mother was heterozygous carrier for this mutation and his sister did not have any mutation. Flow cytometric analysis for CD40LG expression on activated T cells showed highly decreased, but not absent, CD40LG expression. In conclusion, diagnostic delay is a clinical problem for patients with CD40LG deficiency, because of low or normal IgM levels, showing that all the hypogammaglobulinemic patients, not only with high serum IgM levels, but also with normal to low IgM levels, have to be examined for CD40LG expression on activated T lymphocytes. Secondly, type of CD40LG mutations leads to enormous interpatient variations regarding serum IgM levels, CD40LG levels on activated T cells, age at diagnosis, severity of clinical findings, and follow-up therapies with or without hematopoietic stem cell therapy.
- Pitfalls of immunotherapy: lessons from a patient with CTLA-4 haploinsufficiency. [Journal Article]
- AAAllergy Asthma Clin Immunol 2018; 14:65
- CONCLUSIONS: This case demonstrates that autoimmune disease may be the presenting feature of primary immunodeficiency and should be appropriately investigated prior to the commencement of immunotherapy. Genetic clarification of underlying primary immunodeficiency may provide critical clinical information that alters the safety of the proposed treatment strategy.
- Underlying factors of recurrent infections in patients with down syndrome. [Review]
- NCNorth Clin Istanb 2018; 5(2):163-168
- Down syndrome is the most common chromosomal aberration. Patientswith Down syndrome suffer more infections than those without the disease. Underlying immunological disorders are consideredto be the r...
Down syndrome is the most common chromosomal aberration. Patientswith Down syndrome suffer more infections than those without the disease. Underlying immunological disorders are consideredto be the reason for the increasing frequency of infections in patients with Down syndrome. In addition, some anatomical abnormalities in the respiratory tractaccompanying Down syndrome can disturb the innate immunity and contribute to the increase in infection rate. Respiratory tract infections are one of the most common causes of mortality in patients with Down syndrome. Awareness of the underlying reason for frequent respiratory tract infections should result in a decrease in mortality among these patients and contribute to an improvementin their quality of life.
- Congenital pulmonary airway malformation in the asymptomatic adult: A rare presentation. [Journal Article]
- RMRespir Med Case Rep 2018; 25:280-281
- Congenital Pulmonary Airway Malformation (CPAM) is a rare developmental abnormality of the lower respiratory tract, primarily diagnosed in the neonatal period. The most concerning sequelae for patien...
Congenital Pulmonary Airway Malformation (CPAM) is a rare developmental abnormality of the lower respiratory tract, primarily diagnosed in the neonatal period. The most concerning sequelae for patients with CPAM are recurrent respiratory infections and malignancy. Rarely discovered in asymptomatic adults, CPAM presents challenging questions for management. We describe such a case and discuss the risks and benefits of resection.
- Complex congenital cardiac anomalies in the setting of right isomerism in a 31-month-old infant: a case report. [Journal Article]
- JMJ Med Case Rep 2018 Oct 24; 12(1):324
- CONCLUSIONS: Management of patients with heterotaxy syndrome is complex and largely depends on specific anatomy of both cardiac and noncardiac lesions. Cardiac and noncardiac management must be tailored to individual anatomy, including prophylaxis against encapsulated organisms for asplenic patients.
- RSV prophylaxis in premature infants. [Journal Article]
- MPMinerva Pediatr 2018 Oct 18
- Infants born prematurely before 37 weeks of gestational age (GA), have particular anatomical, immunological and metabolic characteristics that predispose them, even in the absence of diseases at birt...
Infants born prematurely before 37 weeks of gestational age (GA), have particular anatomical, immunological and metabolic characteristics that predispose them, even in the absence of diseases at birth, to severe morbidity. Respiratory syncytial virus (RSV) is the leading cause of hospitalization for lower respiratory tract infections (LRTI) in the first year of life, as well as an important cause of respiratory outcomes as recurrent wheezing in industrialized countries or mortality in developing countries. Prematurity is an important risk factor for hospitalization for severe RSV disease, but epidemiological , environmental and demographic risk factors also play a role in RSV infection. Currently, there is no effective antiviral therapy for the treatment of RSV infection, nor the possibility of using maternal immunization or vaccination of children to prevent infection, although numerous preclinical and clinical studies are still ongoing. Passive immunization with palivizumab has been shown to be safe and effective in preventing RSV hospitalization in children at greater risk of contracting a serious infection. Costs associated with palivizumab prophylaxis and its monthly intramuscularly administration has prompted many health institutions of different countries to implement specific recommendations, with the aim of protecting at risk infants for whom RSV infection is likely to cause serious illness or death. The cost-effectiveness ratio of prophylaxis, related to reduce hospitalization costs and the impact of the burden of RSV disease worldwide, greatly affects the drafting and the adoption of specific recommendations and the adherence to them, concerning the passive immunization with palivizumab.
- Fcγ-receptor polymorphisms associated with clinical symptoms in patients with immunoglobulin G subclass deficiency. [Journal Article]
- IDInfect Dis (Lond) 2018 Oct 09; :1-6
- CONCLUSIONS: The gene for classical FcγRIIc-ORF tended to be more frequent in individuals with immunoglobulin G subclass deficiency and the genes for non-classical FcγRIIc-ORF as well as low-binding capacity receptor FcγRIIa-R/R131 were more frequent. Further studies on the FcγR polymorphisms may pave way for identifying individuals that will benefit from immunoglobulin substitution.
- Unilateral Acute Respiratory Distress Syndrome with Contralateral Pulmonary Artery Agenesis: A Rare Scenario. [Journal Article]
- AEAnesth Essays Res 2018 Jul-Sep; 12(3):765-767
- Unilateral pulmonary artery agenesis (UPAA) is a rare condition where the patient may remain asymptomatic for a long period till adulthood. Presentation may be in the form of dyspnea, cough, hemoptys...
Unilateral pulmonary artery agenesis (UPAA) is a rare condition where the patient may remain asymptomatic for a long period till adulthood. Presentation may be in the form of dyspnea, cough, hemoptysis, decreased exercise tolerance, and recurrent respiratory tract infections. Ventilation-perfusion mismatch and excessive blood flow to the normal lung may eventually lead to unilateral acute respiratory distress syndrome (ARDS). We present a case of a 40-year-old gentleman with nonresolving pneumonia who was diagnosed to have unilateral ARDS due to UPAA. Even though ARDS involves bilateral lung, unilateral ARDS which does not show resolution with lung protective strategies should always raise the suspicion of a rare disease like UPAA among clinicians. To date, there is no specific prescribed treatment for UPAA.
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- [Advances in the role of adenoid hypertrophy in the pathogenesis of otitis media with effusion in children]. [Review]
- LCLin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2018; 32(17):1359-1362
- Adenoid hypertrophy(AH) and otitis media with effusion (OME) are both common diseases in pediatric otorhinolaryngology and are often associated with each other. Children are often diagnosed with otit...
Adenoid hypertrophy(AH) and otitis media with effusion (OME) are both common diseases in pediatric otorhinolaryngology and are often associated with each other. Children are often diagnosed with otitis media with effusion and adenoid hypertrophy(OME/AH). Adenoids are immune lymphoid tissues of children's upper respiratory tract, and are important barriers against upper respiratory tract infections.During an upper respiratory tract infection,bacteria or viruses repeatedly stimulate immune lymphoid tissue to cause hyperplasia,and pathological hypertrophy is often accompanied by OME and other related symptoms.In recurrent or chronic OME, hyperproliferative adenoids are usually excised indicating that the two diseases may have a certain correlation. Recently,more and more studies have shown that AH plays an important role in the pathogenesis of OME in children. This article elucidates the role of AH in the pathogenesis of childhood OME from adenoid mechanical obstruction,adenoid bacterial and bacterial biofilm, adenoid local immune regulation, and IgE-mediated allergic reaction.