Recurrent Infections In Children Research Articles

Pidotimod as an Immunomodulator: An Unsung Warrior to Restore Immune Dysregulation in Acute and Chronic Lung Disease

Immune dysregulation has been observed in the majority of the infective and non-infectious respiratory illnesses with impact on the natural course of illness in pediatric to geriatric age groups. Immune regulation between Th1 and Th2 is altered and reversal of proportion between these two differential cells and ultimately homeostasis, with predominance Th2 cells will increase susceptibility for recurrent illnesses; is typically documented in pediatric age groups with first respiratory infection during early neonatal period with respiratory viral etiologies. Apart from recurrent childhood infections, pediatric cases with immune dysregulation will have recurrent wheezing in childhood and are prone for development of childhood asthma in adolescent age groups; if immune dysregulation does not restore in time. In adults, respiratory illnesses due acute viral infective etiology will cause immune dysregulation as documented after coronavirus, influenza and respiratory syncytial virus infections. Immune dysregulation has also been documented in chronic respiratory illnesses such bronchial asthma, chronic bronchitis and COPD. Immune dysregulation will cause recurrent exacerbations in these inflammatory conditions. Pidotimod is an immunomodulator which will work as an immunostimulant molecule due to its unique pharmacological actions on antigen presenting cells, and have novel action on immune cell proliferation and differentiation. In spite of three decades of research of this novel drug Pidotimod, still; it is less used as of today for respiratory ailments in spite of need of a molecule with an immunomodulatory effect for prevention and or cure of illnesses; and modification of natural course of recurrent or relapsing course of chronic illnesses. COVID-19 pandemic has taught us many pathways of immune dysregulation which evolved during natural course of disease and now documented with respiratory viral illnesses such as RSV; and its long-term impact as long covid presenting due to immune dysregulation occurred as a natural course in recovered cases. It’s unclear whether long covid is reversible as of now, but the majority of symptoms have been resolved and shown response to versatile molecules such as steroid, multivitamins, L-arginine, Paxlovid, beta blockers with variable results and long-term outcomes. Pidotimod can be used in acute COVID-19 illness without pneumonia and comorbidities in stable cases in outdoor settings, and also; considered as potential option in long covid cases with recurrent respiratory infections. In this review we have discussed basic aspects of Pidotimod, and its role in immunomodulatory effects in acute and chronic respiratory illness which have shown positive outcomes.

Whole-genome shotgun sequencing unravels the influence of environmental microbial co-infections on the treatment efficacy for severe pediatric infectious diseases.

The microbiome plays a pivotal role in mediating immune deviation during the development of early-life viral infections. Recurrent infections in children are considered a risk factor for disease development. This study delves into the metagenomics of the microbiome in children suffering from severe infections, seeking to identify potential sources of these infections. The aim of this study was to identify the specific microorganisms and factors that significantly influence the treatment duration in patients suffering from severe infections. We sought to understand how these microbial communities and other variables may affect the treatment duration and the use of antibiotics of these patients with severe infections. Whole-genome shotgun sequencing was conducted on samples collected from children aged 0-14 years with severe infections, admitted to the Pediatrics Department of Xiamen First Hospital. The Kraken2 algorithm was used for taxonomic identification from sequence reads, and linear mixed models were employed to identify significant microorganisms influencing treatment duration. Colwellia, Cryptococcus, and Citrobacter were found to significantly correlate with the duration of clinical treatment. Further analysis using propensity score matching (PSM) and rank-sum test identified clinical indicators significantly associated with the presence of these microorganisms. Using a linear mixed model after removed the outliers, we identified that the abundance of Colwellia, Cryptococcus, and Citrobacter significantly influences the treatment duration. The presence of these microorganisms is associated with a longer treatment duration for patients. Furthermore, these microorganisms were found to impact various clinical measures. Notably, an increase in hospitalization durations and medication costs was observed in patients with these microorganisms. In patients with Colwellia, Cryptococcus, and Citrobacter, we discover significant differences in platelets levels. We also find that in patients with Cryptococcus, white blood cells, hemoglobin, and neutrophils levels are lower. These findings suggest that Colwellia, Cryptococcus, and Citrobacter, particularly Cryptococcus, could potentially contribute to the severity of infections observed in this cohort, possibly as co-infections. These microorganisms warrant further investigation into their pathogenic roles and mechanisms of action, as their presence in combination with disease-causing organisms may have a synergistic effect on disease severity. Understanding the interplay between these microorganisms and pathogenic agents could provide valuable insights into the complex nature of severe pediatric infections and guide the development of targeted therapeutic strategies.

Heterogeneous phenotype of autoinflammatory disease in a patient with mutations in NOD2 and MEFV genes

Background: Autoinflammatory diseases are a genetically heterogeneous group of conditions characterized by excessive activation of the innate immune system. They frequently present with overlapping features, particularly in cases of digenic or polygenic inheritance. The most common cause of autoinflammation arises from causative variants in the MEFV gene, responsible for familial Mediterranean fever. Clinical features include recurrent episodes of fever with serositis and amyloidosis. Individuals with variants in MEFV that present atypically with heterogeneous autoinflammatory features have also been described. Notably, gene modifiers of MEFV, such as NOD2 encoding an intracellular bacterial sensor, can result in more severe disease. NOD2 underlies a number of autoinflammatory and immunodeficiency conditions, including Blau syndrome. To date, Blau syndrome has not been described in the context of MEFV. Aim: To expand the presentation and phenotype of autoinflammatory disease associated with defects in the NOD2 and MEFV genes. Methods: A retrospective review of the patient’s chart was performed, including family history, medical history, immune laboratory evaluation, and genetics. Results: We describe here a 68-year-old male with a remarkable medical history since childhood of skin rash, erythroderma, recurrent infections, autoinflammation, arthritis, uveitis, and malignancy. A significant family history of cancer and autoinflammation was noted. Genetic work-up involving a 17-gene autoinflammatory panel revealed 3 heterozygous variants of uncertain significance, 2 of which were present in the MEFV gene and one in the NOD2 gene. His features were consistent with an overlapping phenotype of Blau syndrome and atypical FMF. Conclusion: Heterozygous variants in NOD2 and MEFV can result in a spectrum of autoinflammatory disorders with a heterogeneous phenotype. The NOD2 variant identified in our patient has not previously been associated with Blau syndrome. Statement of Novelty: We describe a patient harbouring heterozygous mutations in the MEFV and NOD2 genes marked by recurrent childhood infections.

33904 Early onset Merkel cell carcinoma in patients with XMEN disease

Background: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer frequently caused by Merkel cell polyomavirus (MCPyV). The median age for MCC diagnosis is 75 years, and MCC is vanishingly rare in patients under 40. We describe 3 patients with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (XMEN) who developed MCC before age 25. XMEN disease is a rare immunodeficiency associated with lymphoma and caused by mutations in the magnesium transporter 1 (MAGT1) gene. Methods: Retrospective chart review for 3 individuals with MCC and XMEN disease. Results: Patient 1 had a history of recurrent childhood infections and splenomegaly and presented at 14 years of age with metastatic MCC that was treated with high-intensity chemotherapy, radiation therapy, and an autologous stem cell transplant. Patient 2 had a history of chronic EBV viremia and recurrent infections and presented at age 22 with Stage III MCC that was treated with surgical resection and radiotherapy. Patient 3 had a history of thrombocytopenia, splenomegaly, and recurrent infections and developed Stage I MCC at age 24 that was treated with surgical resection and radiotherapy. All three patients had MCPyV positive tumors. The patients are alive and tumor-free 13, 4, and 9 years after diagnosis, respectively. Conclusion: Although immunosuppression increases MCC incidence, XMEN disease is associated with a risk for early onset MCC not observed in other primary immunodeficiencies. The MCPyV positivity and prolonged survival in these 3 cases is also atypical for immunosuppressed patients with MCC.

Characterization of a new cytokine complex from the IL-6/IL-12 family

Abstract Cardiotrophin-like cytokine factor 1 (CLCF1) is a neurotrophic factor initially identified as a B lymphocyte stimulating factor. Mutations in CLCF1 cause type 2 Cold-Induced Sweating Syndrome, a severe multisystem disorder coupled with recurrent childhood infections. The CLCF1-CRLF1 composite cytokine mediate its neurotrophic effects via the CNTF receptor (CNTFR). Although immune cells do not express CNTFR, immunological activities of CLCF1 have been described, suggesting the existence of an alternative receptor. Preliminary results suggest that CLCF1 can associate with the Epstein-Barr virus-induced gene 3(EBI3). EBI3 is a subunit of the composite cytokines IL-27, IL-35 and IL-39, which exhibits immunoregulatory functions. Our hypothesis is that CLCF1 associates with EBI3 to activate an alternative receptor expressed by immune cells. The aim of the project is to identify the cells producing CLCF1/EBI3, to define its receptor and to characterize the influence of CLCF1/EBI3 on lymphocyte proliferation, differentiation, and function. We find that EBI3 and CLCF1 subunits can associate extracellularly to form a CLCF1/EBI3 complex. Moreover, we uncovered that this complex can bind to IL-12Rß1, IL-23R and CNTFRα receptor chains. Altogether, our data strongly suggest that the CLCF1/EBI3 complex is likely to assemble in vivo and act as a cytokine through known receptor chains. Overall, defining the cellular targets and biological activities of CLCF1/EBI3 will pave the way for the development of treatments in autoimmune diseases involving CLCF1 and EBI3, adding to the increasing number of biologic drugs targeting cytokines, their receptors, or signaling pathways that are used clinically to treat inflammatory diseases. Supported by IRSC (RNI00404)

Prolidase deficiency, a rare inborn error of immunity, clinical phenotypes, immunological features, and proposed treatments in twins

BackgroundProlidase deficiency (PD) is an autosomal recessive inborn multisystemic disease caused by mutations in the PEPD gene encoding the enzyme prolidase D, leading to defects in turnover of proline-containing proteins, such as collagen. PD is categorized as a metabolic disease, but also as an inborn error of immunity. PD presents with a range of findings including dysmorphic features, intellectual disabilities, recurrent infections, intractable skin ulceration, autoimmunity, and splenomegaly. Despite symptoms of immune dysregulation, only very limited immunologic assessments have been reported and standard therapies for PD have not been described. We report twin females with PD, including comprehensive immunologic profiles and treatment modalities used.Case presentationPatient 1 had recurrent infections in childhood. At age 13, she presented with telangiectasia, followed by painful, refractory skin ulcerations on her lower limbs, where skin biopsy excluded vasculitis. She had typical dysmorphic features of PD. Next-generation sequencing revealed pathogenic compound heterozygous mutations (premature stop codons) in the PEPD gene. Patient 2 had the same mutations, typical PD facial features, atopy, and telangiectasias, but no skin ulceration. Both patients had imidodipeptiduria. Lymphocyte subset analysis revealed low-normal frequency of Treg cells and decreased frequency of expression of the checkpoint molecule CTLA-4 in CD4+ TEM cells. Analysis of Th1, Th2, and Th17 profiles revealed increased inflammatory IL-17+ CD8+ TEM cells in both patients and overexpression of the activation marker HLA-DR on CD4+ TEM cells, reflecting a highly activated proinflammatory state. Neither PD patient had specific antibody deficiencies despite low CD4+CXCR5+ Tfh cells and low class-switched memory B cells. Plasma IL-18 levels were exceptionally high.ConclusionsImmunologic abnormalities including skewed frequencies of activated inflammatory CD4+ and CD8+ TEM cells, decreased CTLA-4 expression, and defects in memory B cells may be a feature of immune dysregulation associated with PD; however, a larger sample size is required to validate these findings. The high IL-18 plasma levels suggest underlying autoinflammatory processes.

Diagnostic Challenge in Boy with Recurrent Meningitis

Recurrent infections in children ranging from simple condition as upper respiratory tract infection which may be normal in this age to more serious infection as in deep seated infection. Meningitis is one of serious infection. Recurrent meningitis must be taken seriously and looking for causes and appropriate management. The aim of this case report is to present a rare case with serious complication. The other issue is to increase the awareness of cerebrospinal leaks among general pediatrics and general practitioners.

Prior tonsillectomy and subsequent risk of breast cancer in females: Systematic review and meta-analysis.

10568 Background: Exposure to recurrent infections in childhood was linked to an increased risk of cancer in adulthood. There is also evidence that a history of tonsillectomy, a procedure often performed in children with recurrent infections, is linked to an increased risk of leukemia, and Hodgkin lymphoma. Tonsillectomy could be directly associated with cancer risk or it could be a proxy for another risk factor such as recurrent infections and chronic inflammation. Nevertheless, the role of recurrent childhood infections and tonsillectomy on the one hand, and the risk of breast cancer (BC) in adulthood remain understudied. Our study aims to verify whether a history of tonsillectomy increases the risk of BC in women. Methods: A systematic review was conducted using PubMed, Google Scholar, Scopus, Embase and Web of Science databases from inception through November 2020 to identify the studies which explored the association between history of tonsillectomy and BC in females. The Newcastle Ottawa Scale was used to assess the quality of included studies. Odds ratio (OR) was used to measure effect size. The Random/Fixed effects model was applied to synthesize the associations between tonsillectomy and BC risk based on heterogeneity. Heterogeneity was assessed using the I-squared statistic. A forest plot was generated, and publication bias was assessed. The leave-one-out sensitivity analysis was performed to check if results were driven by a single study. Results: Seven studies with a total of 7259 patients were included in our analysis; out of them, 2200 patients were diagnosed with BC. Patients with a history of tonsillectomy (n = 2843) showed higher subsequent risk of developing BC (OR = 1.252; 95% CI = 1.115 - 1.406; P < 0.001; I2 = 9%) as compared to patients without a history of tonsillectomy (n = 4416). Using the leave-one-out sensitivity analysis to iteratively remove one study at a time, we confirmed that no single study had a substantial influence on the overall effect size. Conclusions: Our study supports and confirms the evidence that a history of tonsillectomy is associated with an increased risk of breast cancer. These findings are also an argument in support of the hypothesis that recurrent childhood infections are linked with adulthood breast cancer.

A rare condition masquerading as lung cancer

A 63-year-old woman was referred to the lung cancer clinic after presenting to the emergency department with a 10-day history of fever, chest tightness and breathlessness. Chest X-ray showed a...

Is it possible to prevent respiratory pathology?

Acute respiratory infections are the most common reason to consult a paediatrician. Children, especially during critical periods of immune response, are one of the most vulnerable groups to infections. The prevention of recurring respiratory infections is very important, especially from the beginning of attending pre-school and school facilities. Since ancient times, preventive measures such as rational daily routine, sufficient physical activity, correction of nutritional status, phytotherapy and homeopathic treatment have been used. In recent years these children have been optimising their vitamin D status and taking antioxidant vitamins, micro- and macronutrients. To date, as a result of innovative research on the human microbiome, information has emerged on its impact on the human body as a whole. The connection of the intestinal microbiota with the brain (gut-brain axis), with the respiratory tract (gut-lung axis), the cardiovascular system, kidneys and even mental health has been proved. The use of multistrain and multispecies probiotics in the prevention of recurrent infections in children opens up new opportunities to influence the child’s immune response and to form food tolerance. Today, a new multistrain multispecies probiotic (manufacturer ADM Protexin, UK) for the prevention of recurrent respiratory infections in children has appeared on the market. Studies have shown that using several strains of lactobacillus contained in this probiotic leads to more consistent results than monostrains and placebo in the prevention of respiratory diseases. Given the problem of antibiotic resistance, especially in young children, the new possibilities of preventing acute respiratory diseases in children using multistrain and multispecies probiotics make it possible not only to reduce the number and severity of episodes of acute respiratory infections, but also to reduce the frequency of antibiotic use.

Early childhood infections, antistreptococcal and basal ganglia antibodies in adult ADHD: a preliminary study

BackgroundTo explore the relationship between adult Attention Deficit/ Hyperactivity Disorder (ADHD), antistreptococcal titers, ABGA, and recurrent infections during early childhood.MethodChildhood history of recurrent infections and a blood sample were collected in a sample of DSM-IV adult outpatients with ADHD. The anti-streptolysin O (ASO), anti-deoxyribonuclease B (anti-DNase B), and anti-basal ganglia antibodies (ABGA) titers were determined in patient plasma by enzyme-linked immunosorbent assay (ELISA). Titers positivity was evaluated following manufacturer’s specifications. Absolute titers were also collected as continuous variables.ResultsFourteen out of 22 (63.6%) have had recurrent infections in childhood (i.e., seven, 31.8%, have had tonsillitis or adenoiditis and seven, 31.8%, have had any other infections). Eighteen patients (81.9%) were positive for anti-DNase B, five (22.7%) for ASO, and 4 (18.2%) were positive for both of them. Five participants (22.7%) were ABGA positive, whereas only two (9.1%) were positive for all three antibodies.Conclusionspatients with ADHD might be more prone to infections during childhood and subclinical streptococcal infections during adulthood. Moreover, they seem to have an increased risk for basal ganglia autoimmunity in adulthood. Both infections and the ensuing acquired autoimmunity could influence the neurodevelopmental process, by contributing, at least in part, to the ADHD pathogenesis.

M230 EVALUATION OF IMMUNE DEFICIENCY IN A 72 YEAR OLD PATIENT WHO LIVED BY CHERNOBYL

This is a 72-year-old Russian female with history of multiple cancers and recently with recurrent infection. Patient was referred by infectious disease due to recurrent lung infection and cellulitis of unknown etiology. History was negative for recurrent childhood infections or family members with recurrent infection. This case was done by telemedicine, so no exam was able to be done. In reviewing the medical records, the chest CT showed some non-specific lesions and possible bronchiectasis. Her labs showed IGG1 subtype deficiency. In the history. I asked where she immigrated from in Russia and she said she lived near Chernobyl in 1986 during the nuclear reactor melt down. Our research revealed that long term immune system changes have been shown to occur following high dose radiation exposure including antibody deficiency and reduction of lymphocyte function. We did further labs including Lymphocyte Mitogen Stimulation with multiple agents since low response was reported as a sequelae of high dose radiation.

Hyper-IgE syndrome: A rare cause of recurrent infections in children

Hyper-IgE syndrome: A rare cause of recurrent infections in children

Effects of Pidotimod on recurrent respiratory infections in children with Down syndrome: a retrospective Italian study

BackgroundChildren with Down syndrome (DS) show a high susceptibility to recurrent infections (RI), caused by immune defects and abnormalities of the airways. Our goal was to investigate the effects of Pidotimod on RI prevention in children with DS, comparing immune and clinical parameters before (T0) and after (T1) the treatment with Pidotimod.MethodsThe study was conducted at the Down syndrome outpatient Center of Bambino Gesù Children’s Hospital, in Rome. We reviewed the medical records of all children with a positive history for RI and who received oral prophylaxis of Pidotimod from September 2016 to February 2017.ResultsThirty-three children met the inclusion criteria (males: 51.5%; average age: 6 years ±SD: 3). We found a significant decrease in the number of children with upper respiratory infections (82% at T0 vs 24% at T1; p = 0,0001) and with lower respiratory infections (36% at T0 vs 9% at T1; p = 0.003) after treatment with Pidotimod. We also demonstrated a significant decrease in the number of children hospitalized for respiratory infections (18% at T0 vs 3% at T1; p = 0.03). We measured T and B cells in the peripheral blood and B cell function in vitro at T0 and T1. We found that the response to CpG improved at T1. A significant increase of B cell frequency (p = 0.0009), B cell proliferation (p = 0.0278) and IgM secretion (p = 0.0478) were observed in children with DS after treatment.ConclusionsOur results provided evidence that Pidotimod may be able to prevent RI in children with Down syndrome.

Comparison of Primary and Recurrent Urinary Tract Infections in Children.

AimWe aimed to compare the demographic and ultrasound data regarding first-episode urinary tract infections with recurrent infections in children.MethodsA total of 509 children aged 0-16 years who were diagnosed to have a urinary tract infection (UTI) as confirmed with positive urinary culture tests were retrospectively investigated. A comparison of baseline parameters, responsible pathogen incidences, and ultrasound findings was made between children who had a single episode of UTI (n=418, 82.1%) with those having second or more recurrent episodes of urinary tract infection (n=91, 17.9%).ResultsThe mean age of children with a single episode of urinary tract infection was significantly lower than those who had recurrent urinary tract infection (5.33±4.38 vs. 7.01±4.83 years, p=0.003). Incidences of Escherichia coli and Enterococcus faecalis was significantly higher in patients with recurrent urinary tract infection than those who had single episode (n=315, 75.4% vs. n=80, 87.9%, p=0.009 and n=8, 1.9% vs. n=9, 9.9%, p<0.001, respectively). An abnormal ultrasound was significantly more common in patients with recurrent urinary tract infection than those who had a single episode (n=41, 54.6% vs. n=59, 22.7%). Increased renal parenchymal echogenicity (p=0.002), bladder cystitis (p=0.01) and hydronephrosis (p<0.001) were significantly more common in patients with recurrent urinary tract infection than those who had a single episode of urinary tract infection.ConclusionEscherichia coli and Enterococcus faecalis were the most common responsible pathogens in recurrent urinary tract infections. Structural changes, such as hydronephrosis and bladder cystitis, are likely to have an important role in the etiology of children with recurrent urinary tract infection.

ACUTE RESPIRATORY RECURRENT INFECTIONS IN CHILDREN

Introduction. Insufficient research work on the study of local immunity in children with frequent respiratory recurrent diseases has become the basis for this work. Goal. To study the negative impact of various pathogenic factors on the formation of acute respiratory recurrent infections in children. Materials and methods. 201 children under 3 years of age and 219 children from 3 to 7 years old who attended children's preschools in Kyiv were observed in the dynamics. Indices of local immunity, by the content of immunoglobulins in the secretion of the nasal passages, were studied in comparison with the data of the anamnesis and clinical examination of children; with functional condition of the nasal mucosa (presence of catarrhal phenomena); with the presence and excretion of viral and bacterial microflora in the upper respiratory tract; with the presence of chronic foci of infection in the nasopharynx (tonsillitis, adenotonitis); with a period that has elapsed after preventive vaccinations and transferred respiratory diseases. Research results. Based on the obtained data, changes in local immunity in the examined children were detected under the influence of factors of external and internal environment: birth of children from pathological pregnancy and childbirth; presence of hypochromic anemia, exudative diathesis, chronic tonsillitis of staphylococcal etiology, adenotonsillitis, recurrent and asthmatic bronchitis in children; high infection rate of children with viruses, pathogenicity of pathogenic staphylococcus and streptococcus, fungi of the genus Candida. It was found that the lowest frequency of detection of immunoglobulins of all classes was observed in children with streptococcus in pharynx and its associations with staphylococcus. Conclusions. The published data on the value of local immunity in terms of immunoglobulins in children with frequent respiratory recurrent diseases and its tendency to various changes under the influence of external and internal environmental factors indicate the feasibility of improving treatment and prevention measures, which include the use of agents that enhance the effectiveness of local respiratory protection.

Recent Advances in Gene Therapy and Modeling of Chronic Granulomatous Disease

The Chronic granulomatous disease (CGD) is a primary immunodeficiency that characterized by mutations in phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, resulting in deficient antimicrobial activity of phagocytic cells and recurrent childhood infections. Hematopoietic stem cell transplantation (HSCT) is a curative option for patients with human leukocyte antigen (HLA) matched donor, when conventional cares and therapies fail. However, in many cases when the patients have not an HLA-matched donor, they need to a method to recapitulate the function of the affected gene within the patient's own cells. Gene therapy is a promising approach for CGD. While, the success of retroviral or lentiviral vectors in gene therapy for CGD has been hampered by random integration and insertional activation of proto-oncogenes. These serious adverse events led to improvement and generations of viral vectors with increased safety characteristics. Gene therapy continues to progress and the advent of new technologies, such as engineered endonucleases that have shown a great promise for the treatment of genetic disease. This review focuses on the application of gene therapy for the CGD, the limitations encountered in current clinical trials, advantages and disadvantages of endonucleases in gene correction and modeling with CRISPR/Cas9 approach.

Self-reported functional health status following interrupted aortic arch repair: A Congenital Heart Surgeons' Society Study

ObjectivesImproved survival after congenital heart surgery has led to interest in functional health status. We sought to identify factors associated with self-reported functional health status in adolescents and young adults with repaired interrupted aortic arch. MethodsFollow-up of survivors (aged 13-24 years) from a 1987 to 1997 inception cohort of neonates included completion of functional health status questionnaires (Child Health Questionnaire-CF87 [age <18 years, n = 51] or the Short Form [SF]-36 [age ≥18 years, n = 66]) and another about 22q11 deletion syndrome (22q11DS) features (n = 141). Factors associated with functional health status domains were determined using multivariable linear regression analysis. ResultsDomain scores of respondents were significantly greater than norms in 2 of 9 Child Health Questionnaire-CF87 and 4 of 10 SF-36 domains and only lower in the physical functioning domain of the SF-36. Factors most commonly associated with lower scores included those suggestive of 22q11DS (low calcium levels, recurrent childhood infections, genetic testing/diagnosis, abnormal facial features, hearing deficits), the presence of self-reported behavioral and mental health problems, and a greater number of procedures. Factors explained between 10% and 70% of domain score variability (R2 = 0.10-0.70, adj-R2 = 0.09-0.66). Of note, morphology and repair type had a minor contribution. ConclusionsMorbidities associated with 22q11DS, psychosocial issues, and recurrent medical issues affect functional health status more than initial morphology and repair in this population. Nonetheless, these patients largely perceive themselves as better than their peers. This demonstrates the chronic nature of interrupted aortic arch and suggests the need for strategies to decrease reinterventions and for evaluation of mental health and genetic issues to manage associated deteriorations.

17α-Hydroxylase Deficiency is an Underdiagnosed Disease: High Frequency of Misdiagnoses in a Large Cohort of Brazilian Patients

17α-Hydroxylase deficiency (P450c17D) is characterized by hypogonadism and mineralocorticoid hypertension. We aimed to estimate the relative incidence and spectrum of preliminary misdiagnoses in Brazilian P450c17D patients. In this cross-sectional study, we reviewed, updated, and analyzed data of 40 P450c17D patients (21 XY, 19 XX). Complete data were unavailable for 2 patients. Seven patients were relatives of an index case. Of the 31 index cases, 29 (94%) received a total of 16 misdiagnoses (1-4 per patient) before confirmation of P450c17D. Essential hypertension (55%), pure gonadal dysgenesis (35%), and androgen resistance syndrome (21%) were the most frequent misdiagnoses. Median ages at initial and final diagnosis were 13.2 and 16.5 years, respectively, with an average interval to diagnosis of 3.2 years. Initially, 38 (95%) patients had hypertension, and 75% had hypokalemia. Primary amenorrhea and sexual infantilism were present in 95% patients, and 73% were at Tanner stage I. All had low-to-undetectable estrogens and androgens with elevated gonadotropins and progesterone (580 ± 53 ng/dL). Several had recurrent infections in childhood and neurological issues prior to final diagnosis and/or had siblings who died of infectious diseases or unknown causes before puberty. The high percentage of prior misdiagnoses in P450c17D patients may be attributable to the rarity of and relative unfamiliarity with the disease, its varied clinical presentation, and the limited access to critical steroid dosages and genotyping. Reduced sex steroids, and elevated gonadotropins and progesterone levels, in addition to mineralocorticoid hypertension, are pathognomonic of P450c17D. CYP17A1 gene mutations provide a definitive diagnosis. ACTH = adrenocorticotropic hormone CAH = congenital adrenal hyperplasia CYP17A1 = 17α-hydroxylase enzyme DOC = deoxycorticosterone HH = hypergonadotropic hypogonadism P450c17D = 17α-hydroxylase deficiency TS = Tanner stage.

Antibiotics, S aureus Colonization, and Recurrent Skin Infections

Research Article| February 01 2018 Antibiotics, S aureus Colonization, and Recurrent Skin Infections AAP Grand Rounds (2018) 39 (2): 16. https://doi.org/10.1542/gr.39-2-16 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Antibiotics, S aureus Colonization, and Recurrent Skin Infections. AAP Grand Rounds February 2018; 39 (2): 16. https://doi.org/10.1542/gr.39-2-16 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: microbial colonization, skin diseases, infectious, staphylococcus aureus, skin and soft tissue infections, clindamycin Source: Hogan PG, Rodriguez M, Spenner AM, et al. Impact of systemic antibiotics on Staphylococcus aureus colonization and recurrent skin infection [published online ahead of print August 24, 2017. Clin Infect Dis. doi: https://doi.org/10.1093/cid/cix754 Investigators from Washington University, St. Louis, MO, and Southern Illinois University, Springfield, IL, assessed the effect of systemic antibiotics prescribed at the time of incision and drainage (I&D) for Staphylococcus aureus skin and soft tissue infections (SSTI) on rates of future colonization and recurrent infections in children. The investigators combined data from a series of prospective studies, conducted in patients <21 years old with S aureus SSTI since 2008. At the time of I&D (baseline), swabs of the anterior nares, inguinal folds, and axillae of study participants were obtained. For the current study, only children who had S aureus colonization at one or more of these sites were included. Additional data collected at baseline included demographics, decolonization measures (intranasal mupirocin, dilute bleach, or chlorhexidine body washes), whether the infecting S aureus was methicillin-sensitive (MSSA) or resistant (MRSA), and whether the child received antibiotics recommended by the Infectious Diseases Society of America (eg, clindamycin or trimethoprim-sulfamethoxazole [TMP-SMZ]).1 Repeat swabs to determine colonization status were done up to 3 months after baseline. In addition, follow-up data were collected for up to a year after baseline to assess for recurrent SSTI. Cox regression was used to assess the association between use of a guideline-recommended antibiotic at baseline on future colonization or recurrent SSTI, after adjusting for age, race, SSTI isolate (MRSA or MSSA), and number of anatomic sites colonized at baseline. Data were analyzed on 383 children with a median age of 3 years. Overall, 81% of baseline SSTI were caused by MRSA. Baseline colonization was most often detected in inguinal folds, followed by anterior nares; 46% of study participants were colonized at multiple sites. At the time of I&D, 93% of children were prescribed a guideline-recommended antibiotic (clindamycin or TMP-SMZ). Follow-up colonization data were collected on 357 participants. The risk of S aureus colonization at follow-up was significantly lower for children receiving recommended antibiotics compared to those receiving non-recommended or no antibiotics at baseline (colonization rates 48% and 77%, respectively, adjusted hazard ratio [aHR] 0.49, 95% CI 0.30, 0.79). Children receiving clindamycin at baseline were significantly less likely to be colonized at follow-up than those receiving TMP-SMZ (44% and 57%, respectively; P = .03). Recurrent SSTI occurred in 40% of children receiving a recommended antibiotic at baseline vs 64% of those receiving a non-recommended or no antibiotic (aHR = 0.57, 95% CI 0.34, 0.94). The authors conclude that use of clindamycin or TMP-SMZ at the time of I&D in children with an SSTI caused by S aureus reduces the risk of future colonization and rates of recurrent SSTI. Dr Dubik has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. The results of this study join others supporting... You do not currently have access to this content.