Longitudinal changes in bone mineral density in children with inflammatory bowel diseases.

AIM: Children with inflammatory bowel disease (IBD) are prone to low bone mineral density (BMD). Our aim was to assess longitudinal changes in BMD in this population. METHODS: A retrospective longitudinal study of children with IBD, treated at two tertiary centres in Israel, who underwent two BMD measurements by dual-energy X-ray absorptiometry (DXA). Changes in lumbar spine BMD (∆L1-4 z-scores) were examined for correlations with clinical characteristics. RESULTS: The cohort included 41 patients (age at diagnosis 12.1 ± 3.5 years, 23 females).The mean interval between the scans was 3.4 ± 2.0 years. There was a trend towards improvement in L1-4 z-scores (-1.64 ± 1.02 vs -1.45 ± 0.83, P = .12). ∆L1-4 z-scores correlated positively with ∆weight-standard deviation scores (SDS), ∆height-SDS and ∆BMI-SDS, and with age at the second scan (R = .55, P < .01; R = .42, P < .01; R = .42, P = .01; R = .35, P = .02, respectively); and negatively with L1-4 z-scores at the first scan (R = -.63, P < .01). Stepwise linear regression analysis identified the first scan L1-4 z-scores and ∆weight-SDS as independent predictors of ∆L1-4 z-scores. An L1-4 z-score ≤-2 at the first DXA scan was associated with significant improvement at the second scan. CONCLUSION: Improvement in BMD was more pronounced in children who gained weight or whose BMD was low at the first scan.

Frequencies of 4 tumor-infiltrating lymphocytes potently predict survival in glioblastoma, an immune desert.

BACKGROUND: GBM is an aggressive grade 4 primary brain tumor (BT), with a 5%-13% 5-year survival. Most human GBMs manifest as immunologically "cold" tumors or "immune deserts," yet the promoting or suppressive roles of specific lymphocytes within the GBM tumor microenvironment (TME) is of considerable debate. METHODS: We used meticulous multiparametric flow cytometry (FC) to determine the lymphocytic frequencies in 102 GBMs, lower-grade gliomas, brain metastases, and nontumorous brain specimen. FC-attained frequencies were compared with frequencies estimated by "digital cytometry." The FC-derived data were combined with the patients' demographic, clinical, molecular, histopathological, radiological, and survival data. RESULTS: Comparison of FC-derived data to CIBERSORT-estimated data revealed the poor capacity of digital cytometry to estimate cell frequencies below 0.2%, the frequency range of most immune cells in BTs. Isocitrate dehydrogenase (IDH) mutation status was found to affect TME composition more than the gliomas' pathological grade. Combining FC and survival data disclosed that unlike other cancer types, the frequency of helper T cells (Th) and cytotoxic T lymphocytes (CTL) correlated negatively with glioma survival. In contrast, the frequencies of γδ-T cells and CD56bright natural killer cells correlated positively with survival. A composite parameter combining the frequencies of these 4 tumoral lymphocytes separated the survival curves of GBM patients with a median difference of 10 months (FC-derived data; P < .0001, discovery cohort), or 4.1 months (CIBERSORT-estimated data; P = .01, validation cohort). CONCLUSIONS: The frequencies of 4 TME lymphocytes strongly correlate with the survival of patients with GBM, a tumor considered an immune desert.