Screening Newborns for Low T Cell Receptor Excision Circles (TRECs) Fails to Detect Immunodeficiency, Centromeric Instability, and Facial Anomalies Syndrome.

BACKGROUND: Assessment of T-cell receptor excision circles (TRECs) in dried blood spots of newborns allows the detection of severe combined immunodeficiency (SCID) (T cells <300/µL at birth) with a presumed sensitivity of 100%. TREC screening also identifies patients with selected combined immunodeficiency (CID) (T cells >300/µL, yet <1500/µL at birth). Nevertheless, relevant CIDs that would benefit from early recognition and curative treatment pass undetected. OBJECTIVE: We hypothesized that TREC screening at birth cannot identify CIDs that develop with age. METHODS: We analyzed the number of TRECs in dried blood spots in archived Guthrie cards of 22 children who had been born in the Berlin-Brandenburg area between January 2006 and November 2018 and who had undergone hematopoietic stem-cell transplantation (HSCT) for inborn errors of immunity. RESULTS: All patients with SCID would have been identified by TREC screening, but only 4 of 6 with CID. One of these patients had immunodeficiency, centromeric instability, and facial anomalies syndrome type 2 (ICF2). Two of 3 patients with ICF whom we have been following up at our institution had TREC numbers above the cutoff value suggestive of SCID at birth. Yet all patients with ICF had a severe clinical course that would have justified earlier HSCT. CONCLUSIONS: In ICF, naïve T cells may be present at birth, yet they decline with age. Therefore, TREC screening cannot identify these patients. Early recognition is nevertheless crucial, as patients with ICF benefit from HSCT early in life.

Diffusion-weighted imaging with acquisition of three b-values for response evaluation of neuroendocrine liver metastases undergoing selective internal radiotherapy.

OBJECTIVES: To evaluate diffusion-weighted MRI with acquisition of three b-values and calculation of fractioned ADCs for response evaluation of neuroendocrine liver metastases undergoing selective internal radiotherapy (SIRT). METHODS: Ten consecutive patients with neuroendocrine liver metastases underwent MRI before and following SIRT. Diffusion-weighted imaging included acquisition of the b-values 0, 50 and 800 s/mm(2) and calculation of ADC(50,800), ADC(0,50) and ADC(0,800) maps. According to therapy response, lesions were categorised into group A [≥20% reduction of the longest diameter (LD) in comparison to baseline MRI] and group B (<20% reduction of the LD). RESULTS: Twelve out of 31 metastases were categorised as group A and 19 out of 31 metastases were categorised as group B. Pretherapeutic values of ADC(0,800) and ADC(50,800) did not differ significantly between the two groups; however, ADC(0,50) was 32% lower in group A (P = 0.049). ADC(0,800) and ADC(50,800) increased significantly after therapy in both groups, however, group differences were not statistically significant. Conversely, the increase in ADC(0,50) was about a factor of 7 larger in group A than in group B (P = 0.023). CONCLUSIONS: Our study showed that the ADC(0,50) is a promising biomarker for response assessment of neuroendocrine liver metastases following SIRT. KEY POINTS: • Diffusion-weighted MRI offers new information about neuroendocrine hepatic metastases. • Evaluation of perfusion and diffusion components requires fractioned apparent diffusion coefficients (ADCs). • Perfusion effects represented by ADC (0.50) can be observed in neuroendocrine metastases. • Pretherapeutic ADC (0.50) was significantly lower in metastases with a response ≥20%. • Such biomarkers may help evaluate liver metastases in patients undergoing therapy.