Impact of newborn screening for SCID on the management of congenital athymia.

BACKGROUND: Newborn screening (NBS) programs for severe combined immunodeficiency facilitate early diagnosis of severe combined immunodeficiency and promote early treatment with hematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS because of severe T-cell lymphopenia. With the expanding introduction of NBS programs, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH) (London, United Kingdom). OBJECTIVE: We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH. METHODS: We compared age at referral and complications between athymic infants diagnosed after clinical presentation (n = 25) and infants identified through NBS (n = 19) who were referred for thymus transplantation at GOSH between October 2019 and February 2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. RESULTS: The infants referred after identification through NBS were significantly younger and had fewer complications, in particular fewer infections. All deaths occurred in the group of those who did not undergo NBS, including 6 patients before and 2 after thymus transplantation because of preexisting infections. In the absence of significant comorbidities or diagnostic uncertainties, timely treatment was achieved more frequently after NBS. Treatment when younger than age 4 months was associated with higher thymic output at 6 and 12 months after transplantation. CONCLUSION: NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation before they acquire infections or other complications and facilitating treatment at a younger age, thus playing an important role in improving their outcomes.

A common complaint a rare disease!

A 2-year-old previously well child presented to the emergency department with temperatures and lethargy. He was pale and looked unwell. He received a fluid bolus and was commenced on intravenous ceftriaxone. Pus was discharging from his left ear with postauricular swelling and erythema. Given clinical concerns, urgent neuroimaging was arranged.

How to interpret a paediatric blood culture.

Blood culture is one of the most important diagnostic tests in medicine, considering the significant morbidity and mortality associated with bloodstream infection (BSI). However, it is an often misused and misinterpreted test in everyday paediatric practice. In this article, we explore the evidence related to paediatric blood cultures, with the aim of providing clear and clinically-relevant recommendations for its judicious use.

Fifteen-minute consultation: What do I do with a baby born to a mother with tuberculosis?

Tuberculosis (TB) remains a considerable disease burden, even in high-income countries such as the UK. In recent years, there has been a change in epidemiology with an increased incidence in those under 30 years old. This increases the proportion of women of childbearing age contracting tuberculosis. There is limited evidence around optimal management of the neonate who has been exposed to tuberculosis; however, we know that neonatal TB is fatal if untreated. It is therefore important to have a framework of how to manage the infants born to these mothers. Good communication between respiratory or infectious diseases physicians treating the expectant mother, maternity and paediatric teams is essential. Prompt assessment of the infant with input from paediatricians with an expertise in paediatric tuberculosis is essential.

What is that rash?

CASE HISTORY: A healthy 15-month-old girl presented to the emergency department with a 24-hour history of fever and rash. The initial blanching rash developed into non-blanching areas with associated leg swelling. She had received no recent medications, had no known drug allergies and no unwell contacts.On examination, she was feverish at 38.6°C, capillary refill time was <2 s with warm peripheries, heart rate 169 bpm and blood pressure 94/59 mm Hg. A palpable purpuric rash was evident on all four limbs and face (figure 1) although the trunk was spared. Her legs were tense and oedematous to the knee.edpract;103/1/25/EDPRACT2016311782F1F1EDPRACT2016311782F1Figure 1Rash at presentation.Initial investigations: Haemoglobin level: 131 g/L, white cell count: 16.6×109/L, neutrophils: 11.1×109/L and platelets: 407×109/LCoagulation screen: normalC reactive protein level: 20 mg/LLactate level: 1.7 mmol/LIntravenous ceftriaxone was commenced following blood culture and meningococcal PCR. The following day, while remaining systemically well, she developed a vesicular rash on her trunk and back (figure 2).edpract;103/1/25/EDPRACT2016311782F2F2EDPRACT2016311782F2Figure 2Vesicular rash. QUESTIONS: What is the diagnosis? Henoch-Schonlein purpura (HSP)Meningococcal septicaemiaAcute haemorrhagic oedema of infancy (AHOI)Vasculitic urticariaGianotti-Crosti syndromeWhat further investigation is required? Check viral serology including Epstein-Barr virus and hepatitis B virusComplement levels and autoimmune screenSkin biopsyLumbar puncture and audiologyNo further investigationHow should this child be managed? Complete 7 days of ceftriaxone treatmentOral aciclovirOral steroidsRegular follow-up with urinalysis and blood pressure monitoringStop antibiotics if cultures were negative at 48 hours and dischargeAnswers are on page▪▪.

ATP and norepinephrine contributions to sympathetic vasoconstriction of tail artery are altered in streptozotocin-diabetic rats.

Sympathetic vasoconstriction is susceptible to diabetes, but contributions made by purinergic neurotransmission in this state have not been investigated. We aimed to evaluate sympathetic vasoconstriction contributions by ATP and norepinephrine in the tail artery from streptozotocin-diabetic rats by using isometric vascular rings. Tail arteries were isolated from rats made diabetic 3 mo earlier with streptozotocin (diabetic group), age-matched nondiabetic rats (nondiabetic injected), age-matched untreated animals (noninjected normal), and age-matched untreated animals in high glucose control Krebs solution (high glucose control). Responses to KCl (60 mM) or nerve stimulus trains of 1-100 impulses were identical in all groups. Electrical stimulation produced progressively greater contractions with increasing impulse numbers. These were partially reduced by suramin (100 microM, P2 antagonist), NF-279 (1 microM, P2X blocker), and phentolamine (2 microM, alpha-blocker). For purinergic antagonists, blockade was greater in diabetic vessels compared with that in others. No differential effect could be detected for phentolamine between groups. Bath-applied ATP (1 nM-1 mM) and norepinephrine (0.1 nM-100 microM) showed increased potency with diabetic group vessels. Desipramine (1 microM, norepinephrine reuptake inhibitor) potentiated neurally evoked responses in all groups equally and increased sensitivity to exogenous norepinephrine in a similar fashion. Histochemical labeling of sympathetic nerves with neuronal marker protein PGP-9.5 and a sympathetic nerve-specific antibody for tyrosine hydroxylase showed no reduction in diabetic innervation density. We demonstrate, for the first time, changes in contributions of ATP and norepinephrine in sympathetic responses of rat tail artery in diabetes, which cannot be accounted for by axonal degeneration or by changes in norepinephrine reuptake.