Value of Urinary Neutrophil Gelatinase-Associated Lipocalin in Diagnosing Urinary Tract Infections in Children: A Systematic Review and Meta-Analysis.

This study presents a comprehensive review of the literature regarding the use of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a diagnostic tool for urinary tract infection (UTI) in children. Meta-analysis was conducted to evaluate the effectiveness of uNGAL in diagnosing UTI and differentiating acute pyelonephritis (APN) from other sites infection in pediatric patients. We searched PubMed, Web of Science, the Cochrane Library and EMBASE for reports published up to January 2023. We only included published literature that addressed the diagnosis of UTI and APN with the use of uNGAL in children aged 0-18 years. Two authors independently reviewed the included studies and extracted the corresponding data according to the inclusion and exclusion criteria. The sensitivity, specificity and area under the curve for each study were pooled by using a bivariate mixed-effects model. A total of 13 studies met the inclusion criteria for this review: 8 reported on uNGAL diagnosis of UTI, 2 on uNGAL diagnosis of APN, and 3 on both UTI and APN. Among all included studies, uNGAL had good sensitivity (0.88, 95% CI 0.79-0.94) and good specificity (0.86, 95% CI 0.78-0.92) for the diagnosis of UTI. The sensitivity and specificity of uNGAL for the diagnosis of APN were 0.79 (95% CI 0.72-0.85) and 0.78 (95% CI 0.50-0.93), respectively. uNGAL has good sensitivity and specificity in the diagnosis of UTI in children and is a promising marker. However, the use of uNGAL still does not provide significant advantages in the diagnosis of APN in children. Consequently, there is a need to optimize and further explore the assay for improved diagnostic accuracy.

T Cells Expanded from PD-1+ Peripheral Blood Lymphocytes Share More Clones with Paired Tumor-Infiltrating Lymphocytes.

Both tumor-infiltrating lymphocytes (TIL) and PD-1+ peripheral blood lymphocytes (PBL) are enriched for tumor-reactive clones recognizing known and unknown tumor antigens. However, the relationship between the T-cell receptor-ß (TCRß) repertoires of the TILs and T cells expanded from paired PD-1+ PBLs, and whether T cells expanded from PD-1+ PBLs can be used to treat patients with cancer as TIL substitutes remain unclear. Here, we established a highly efficient protocol to prepare polyclonal T cells from PD-1+ PBLs. A functional T-cell assay and tetramer staining revealed that cells from PD-1+ PBLs were relatively enriched for tumor-reactive T cells. Furthermore, deep TCRß sequencing data revealed that an average of 11.29% (1.32%-29.06%; P = 0.015; n = 8) tumor-resident clonotypes were found in T cells expanded from paired PD-1+ PBLs, and the mean accumulated frequency of TIL clones found in T cells expanded from PD-1+ PBLs was 35.11% (7.23%-78.02%; P = 0.017; n = 8). Moreover, treatment of four patients, who failed multiline therapy and developed acquired resistance to anti-PD-1, with autologous T cells expanded from PD-1+ PBLs combined with anti-PD-1 antibody elicited objective responses from three of them. These results indicate that T cells expanded from PD-1+ PBLs share more clones with paired TILs and could be used to treat patients with cancer as TIL substitutes. SIGNIFICANCE: This study harnesses the tumor reactivity of PD-1+ PBLs, developing a method to expand T cells from these clones as a potential therapeutic strategy and TIL substitute in patients with cancer.See related commentary by Ladle, p. 1940.

Effect of SGLT2 inhibitor on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study summarizes the evidence from randomized controlled trials (RCTs) to assess the effects of SGLT2 inhibitors on renal function and albuminuria in patients with type 2 diabetes. MATERIALS/METHODS: We searched PubMed, Web of Science, Cochrane Library and EMBASE for reports published up to March 2018 and included RCTs reporting estimated glomerular filtration rate (eGFR) and/or urine albumin/creatinine ratio (UACR) changes. Data extraction and assessment of research quality based on Cochrane risk biasing tools. Data were calculated to represent the standardized mean difference (SMD) for each study, and the SMDs with 95% confidence intervals (CIs) were pooled using a random effects model. RESULTS: Fifty-one studies were included that evaluated eGFR levels, and 17 studies were included that evaluated UACR levels. A meta-analysis showed that SGLT2 inhibitors had no significant effect on eGFR levels (SMD - 0.02, 95% CI - 0.06, 0.03, p = 0.45), and eGFR reduction was observed in the subsets of the duration of the trial 12 < duration ≤ 26 weeks (SMD - 0.08, 95% CI - 0.13, - 0.02, p = 0.005) and mean baseline eGFR < 60 ml/min per 1.73 square meters (SMD - 0.22, 95% CI - 0.37, - 0.07, p = 0.004). We found that SGLT2 inhibitors reduced UACR levels in patients with type 2 diabetes (SMD - 0.11, 95% CI - 0.17, - 0.05, p = 0.0001). Compared with monotherapy, the combination with other hypoglycemic agents can reduce albuminuria levels (SMD - 0.13, 95% CI - 0.19, - 0.06, p < 0.0001). CONCLUSIONS: The effect of SGLT2 inhibitor on eGFR in patients with T2DM was not statistically significant, but it was effective in reducing albuminuria levels.