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Despite similar clinical symptoms, peanut-allergic (PA) individuals may respond quite differently to the same therapeutic interventions.
This study aimed to determine whether inherent ...qualities of cell response at baseline could influence response to peanut oral immunotherapy (PnOIT).
We first performed ex vivo T-cell profiling on peanut-reactive CD154+CD137+ T (pTeff) cells from 90 challenge-confirmed PA individuals. We developed a gating strategy for unbiased assessment of the phenotypic distribution of rare pTeff cells across different memory CD4+ T-cell subsets to define patient immunotype. In longitudinal samples of 29 PA participants enrolled onto the IMPACT trial of PnOIT, we determined whether patient immunotype at baseline could influence response to PnOIT.
Our data emphasize the heterogeneity of pTeff cell responses in PA participants with 2 mutually exclusive phenotypic entities (CCR6−CRTH2+ and CCR6+CRTH2−). Our findings lead us to propose that peanut allergy can be classified broadly into at least 2 discrete subtypes, termed immunotypes, with distinct immunologic and clinical characteristics that are based on the proportion of TH2A pTeff cells. PnOIT induced elimination of TH2A pTeff cells in the context of the IMPACT clinical trial. Only 1 PA patient with a low level of TH2A pTeff cells at baseline experienced long-lasting benefit of remission after PnOIT discontinuation.
Dividing PA patients according to their individual peanut-specific T-cell profile may facilitate patient stratification in clinical settings by identifying which immunotypes might respond best to different therapies.
Introduction
Prenatal sonographic evidence of large, echogenic, or cystic kidneys may indicate any one of a diverse set of disorders including renal ciliopathies, congenital anomalies of the kidney ...and urinary tract (CAKUT), or multisystem syndromic disorders. Systematic transition planning for these infants from
in utero
detection to post-natal nephrology management remains to be established.
Aim of the work
We sought to evaluate the presentation and transition planning for infants identified
in utero
with bilateral renal cystic disease.
Methods
Our retrospective observational study identified 72 pregnancies with bilateral renal cystic disease in a single center from 2012 to 2022; 13 of which had a confirmed renal ciliopathy disorder. Clinical and imaging data, genetic test results, and documentation of postnatal follow-up were collected and compared.
Results
In our suspected renal ciliopathy cohort (
n
= 17), autosomal recessive polycystic disease (ARPKD) was the most common diagnosis (
n
= 4), followed by Bardet-Biedl syndrome (BBS,
n
= 3), autosomal dominant polycystic disease (ADPKD,
n
= 2),
HNF1B
-related disease (
n
= 2), and Meckel-Gruber syndrome (MKS,
n
= 2). Four cases were not genetically resolved. Anhydramnios was observed primarily in fetuses with ARPKD (
n
= 3). Polydactyly (
n
= 3) was detected only in patients with BBS and MKS, cardiac defects (
n
= 6) were identified in fetuses with ARPKD (
n
= 3), MKS (
n
= 2), and BBS (
n
= 1), and abnormalities of the CNS (
n
= 5) were observed in patients with ARPKD (
n
= 1), MKS (
n
= 2), and BBS (
n
= 3). In general, documentation of transition planning was incomplete, with post-natal nephrology management plans established primarily for infants with renal ciliopathies (
n
= 11/13; 85%).
Conclusion
Prenatal sonographic detection of echogenic kidneys should raise suspicion for a broad range of disorders, including renal ciliopathies and CAKUT. Multicenter collaboration will be required to standardize the implementation of transition guidelines for comprehensive nephrology management of infants identified
in utero
with enlarged, echogenic kidneys.
Invasive candidiasis is responsible for ∼ 10% of nosocomial sepsis in very-low-birth-weight infants and is associated with substantial morbidity and mortality. Over the last two decades, the ...antifungal armamentarium against Candida spp. has increased; however, efficacy and safety studies in this population are lacking.
We reviewed the medical literature and extracted information on clinical and observational studies evaluating the use of antifungal agents in neonates with invasive candidiasis.
Efficacy and safety data for antifungals in neonates are lacking, and the majority of studies conducted to date have concentrated on pharmacokinetic/pharmacodynamic evaluations. Unlike other anti-infective agents, efficacy data in the setting of neonatal candidiasis cannot be extrapolated from adult studies due to differences in the pathophysiology of the disease in this population relative to older children and adults. Data for amphotericin B deoxycholate, fluconazole, and micafungin suggest that these are the current agents of choice for this disease in neonates until data for newer antifungal agents become available. For prophylaxis, data from fluconazole randomized controlled trials will be submitted to the regulatory agencies for labeling. Ultimately, the field of therapeutics for neonatal candidiasis will require multidisciplinary collaboration given the numerous challenges associated with conducting clinical trials in neonates.
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