Versiti Blood Center of Wisconsin

PurposeTransepidermal water loss (TEWL) and stratum corneum hydration (SCH) are commonly used to assess epidermal barrier hydration. We investigated the associations of TEWL and SCH levels in newborns and the incidence of atopic dermatitis (AD) within the first 3 months of age.MethodsWe measured SCH and TEWL levels on the cheeks of 330 healthy full-term Vietnamese newborns within 48 hours after birth using a GPSkin Barrier Pro® device (GPOWER Inc., Korea). Subsequently, 233 newborns completed the follow-up via telephone calls over a period of 3 months. Any cases of AD and other skin disorders, including seborrheic dermatitis, diaper dermatitis, perianal dermatitis, or contact dermatitis that developed during the follow-up period, were recorded; AD was diagnosed based on the UK Working Party diagnostic criteria.ResultsA total of 233 newborns were followed up during the first 3 months of age, of whom 29 (12.4%) were diagnosed with AD. An increased risk of AD development was associated with higher TEWL levels within 48 hours after birth (adjusted risk ratio [aRR], 1.31; 95% confidence interval [CI], 1.14–1.51; P < 0.001) and longer gestational age (aRR, 2.71; 95% CI, 1.11–6.65, P = 0.029). A receiver operating characteristic curve analysis indicated that the TEWL levels could serve as a predictive factor for AD development in the first 3 months of life, with an area under the curve of 0.77 (95% CI, 0.67–0.86, P < 0.001).ConclusionsThe TEWL levels and gestational age within 48 hours after birth could serve as predictive factors for the development of AD in the first 3 months of life. This finding establishes a basis for the development of optimal prevention methods for AD.

ABSTRACTHistorically, clonal hematopoiesis (CH) has been recognized as a confounder of cell‐free DNA (cfDNA) testing. Recent evidence now demonstrates the role of CH as a risk factor in health, generating distinct sources of cfDNA that can be leveraged for liquid biopsy diagnostics. Nonetheless, gaps in standardization challenge the advancement of such diagnostics from development to regulatory approval, through clinical trials, and ultimately, to routine implementation. In 2024, the Blood Profiling Atlas in Cancer (BLOODPAC) Consortium, a collaborative infrastructure for developing standards and best practices for liquid biopsy assays, established the CH/clonal hematopoiesis of indeterminate potential (CHIP) Working Group to address the need for accurate identification and removal of CH from liquid biopsy results. As a first step to support the interpretability of CH/CHIP results, the Working Group developed this lexicon to standardize terms and provide a unified vocabulary related to CH and liquid biopsy, DNA sequencing tests, biomarkers, and clinical use cases, facilitating communication within the field. BLOODPAC's CH/CHIP Working Group believes that terminology agreement across these various stakeholders can improve communication in the field and unify future data collection efforts across studies.

Sickle cell disease comprises a group of prevalent inherited disorders defined by an underlying sickle cell allele that forms sickle hemoglobin. The incidence of this disease is rising, with more than 500,000 children born with it globally. The disease carries significant morbidity and mortality. Its only curative treatment was an allogeneic hematopoietic stem cell (HSC) transplant (HSCT) until late 2023, when two one-time gene therapies were approved for treating patients aged 12 years or older with severe sickle cell disease. This work aims to inform readers about these two gene therapies: one lentiviral-based and the other nonviral. The latter is based on the Nobel Prize-winning discovery of clustered, regularly interspaced, short, palindromic repeats (CRISPR)/CRISPR-associated (Cas)9 proteins and single-guide RNA (sgRNA)-based genome editing. Both approved gene therapies require an autologous HSCT with ex vivo genetically edited autologous hematopoietic stem and progenitor cells. Therefore, access to these gene therapies is limited to specialized centers with expertise in HSCTs. This review is meant for students, researchers, and clinical practitioners. It explains the basis for both approved gene therapies, their mechanisms of action, differences, risks, and other lentiviral-based and CRISPR-Cas9-based ex vivo gene therapies for sickle cell disease in clinical development. Additionally, it discusses the current state of preclinical studies for in vivo HSC gene therapy for sickle cell disease, which utilize advanced genome editing technologies developed after CRISPR-Cas9-sgRNA-based genome editing. In vivo HSC gene therapy, after it is clinically developed, would eliminate the need for an HSCT in receiving gene therapy and vastly increase access for numerous patients worldwide, even in low-income countries with the most significant disease burden.