Natural history of infants with non-SCID T cell lymphopenia identified on newborn screen.

Newborn screening (NBS) for severe combined immunodeficiency (SCID) can identify infants with non-SCID T cell lymphopenia (TCL). The purpose of this study was to characterize the natural history and genetic findings of infants with non-SCID TCL identified on NBS. We analyzed data from 80 infants with non-SCID TCL in the mid-Atlantic region between 2012 and 2019. 66 patients underwent genetic testing and 41 (51%) had identified genetic variant(s). The most common genetic variants were thymic defects (33%), defects with unknown mechanisms (12%) and bone marrow production defects (5%). The genetic cohort had significantly lower median initial CD3+, CD4+, CD8+ and CD4/CD45RA+ T cell counts compared to the non-genetic cohort. Thirty-six (45%) had either viral, bacterial, or fungal infection; only one patient had an opportunistic infection (vaccine strain VZV infection). Twenty-six (31%) of patients had resolution of TCL during the study period.

Clopidogrel Hypersensitivity: Pathogenesis, Presentation and Diagnosis.

This paper provides an overview of the pathogenesis, presentation and diagnosis of clopidogrel hypersensitivity. The majority of clopidogrel hypersensitivity cases are due to a T cell mediated Gell and Coombs Type IV reaction. History, histology, and patch testing have shown consistency with a T cell mediated mechanism. Clopidogrel reactions most commonly present as a mild delayed maculopapular erythematous rash 5 to 10 days after introduction of the drug, and do not always require discontinuation of the drug. Severe cutaneous, systemic, and immediate adverse reactions to clopidogrel are rare. For the diagnosis of clopidogrel hypersensitivity, drug causality can be determined using patch testing, or for mild reactions, recurrence of symptoms after drug reintroduction, although neither are required for diagnosis.

Three-dimensional image analysis for staging chronic rhinosinusitis.

BACKGROUND: Traditional methods of staging chronic rhinosinusitis (CRS) through imaging do not differentiate between degrees of partial mucosal sinus inflammation, thus limiting their utility as imaging biomarkers. We hypothesized that software-aided, quantitative measurement of sinus inflammation would generate a metric of disease burden that would correlate with clinical parameters in patients with suspected sinus disease. METHODS: Adults with rhinologic complaints undergoing computed tomography imaging were recruited at an urban, academic, tertiary care center (n = 45 with Lund-Mackay [LM] scores ≥4). Three-dimensional (3D) volumetric image analysis was performed using a semiautomated method to obtain a "Chicago-modified Lund-Mackay" (Chicago MLM) score, which provides a continuous scale to quantify extent of opacification. Linear regression was used to test the association of the Chicago MLM score with concurrent symptoms (Total Nasal Symptom Score [TNSS]) and disease-specific quality of life, based on the Sinonasal Outcome Test-22 (SNOT-22). RESULTS: Chicago MLM scores were significantly associated with both symptoms (p = 0.037) and disease-specific quality of life (p = 0.007). Inflammation in the ethmoid and sphenoid sinuses appeared to influence these associations. These findings were even more robust when analysis was limited to patients with more severe disease (LM >6). CONCLUSION: The quantitative measurement of sinus inflammation by computer-aided 3D analysis correlates modestly with both symptoms and disease-specific quality of life. Posterior sinuses appear to have the greatest impact on these findings, potentially providing an anatomic target for clinicians to base therapy. The Chicago MLM score is a promising imaging biomarker for clinical and research use.

Computer-assisted staging of chronic rhinosinusitis correlates with symptoms.

BACKGROUND: The Lund-Mackay (LM) staging system for chronic rhinosinusitis (CRS) does not correlate with clinical parameters, likely due to its coarse scale. We developed a "Modified Lund Mackay" (MLM) system, which uses a three-dimensional (3D), computerized method to quantify the volume of mucosal inflammation in the sinuses, and sought to determine whether the MLM would correlate with symptoms and disease-specific quality of life. METHODS: We obtained Total Nasal Symptom Score (TNSS) and 22-item Sino-Nasal Outcome Test (SNOT-22) data from 55 adult subjects immediately prior to sinus imaging. The volume of each sinus occupied by mucosal inflammation was measured using MATLAB algorithms created using customized, image analysis software after manual outlining of each sinus. Linear regression was used to model the relationship between the MLM and the SNOT-22 and TNSS. Correlation between the LM and MLM was tested using Spearman's rank correlation coefficient. RESULTS: Adjusting for age, gender, and smoking, a higher symptom burden was associated with increased sinonasal inflammation as captured by the MLM (ß = 0.453, p < 0.013). As expected due to the differences in scales, the LM and MLM scores were significantly different (p < 0.011). No association between MLM and SNOT-22 scores was found. CONCLUSION: The MLM is one of the first imaging-based scoring systems that correlates with sinonasal symptoms. Further development of this custom software, including full automation and validation in larger samples, may yield a biomarker with great utility for both treatment of patients and outcomes assessment in clinical trials.