Background Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to compare the predictive performance of different candidate biomarkers for AKI. Methods In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (> 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence. Results We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio [DOR] 16.2, 95% CI 10.1–25.9), urinary NGAL (DOR 13.8, 95% CI 10.2–18.8), and serum NGAL (DOR 12.6, 95% CI 9.3–17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively. Conclusions Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients. Trial registrationCRD42020207883, October 06, 2020.

Background: In patients with primary aldosteronism (PA), long-term cardiovascular and mortality outcomes after adrenalectomy versus mineralocorticoid receptor antagonist (MRA) have not been compared yet. We aim to compare the clinical outcomes of these patients after treatment. Design and Methods: A systematic review and meta-analysis was conducted by searching PubMed, Cochrane library, and Embase from no start date restriction to Dec 18, 2021. Our composite primary outcomes were long-term all-cause mortality and/or major adverse cardiovascular events (MACE), including coronary artery disease (CAD), stroke, arrhythmia, and congestive heart failure. We adopted the random-effects model and performed subgroup analyses, meta-regression, and trial sequential analysis (TSA). Results: A total of 9 studies with 8,473 adult patients with PA (≥18 years) were enrolled. Lower incidence of composite primary outcomes was observed in the adrenalectomy group (odds ratio (OR): 0.46 [95% CI, 0.38-0.56], P < 0.001). We found lower incidence of all-cause mortality (OR: 0.33 [95% CI, 0.15-0.73], P = 0.006) and MACE (OR: 0.55, [95% CI, 0.40-0.74], P = 0.0001) in the adrenalectomy group. The incidence of CAD (OR: 0.33 [95% CI, 0.15-0.75], P = 0.008), arrhythmias (OR: 0.46 [95% CI, 0.27-0.81], P = 0.007), and congestive heart failure (OR: 0.52 [95% CI, 0.33-0.81], P = 0.004) were also lower in adrenalectomy group. The meta regression showed patient’s age may attenuate the benefits of adrenalectomy on composite primary outcomes (coefficient: 1.084 [95% CI, 1.005-1.169], P = 0.036). TSA demonstrated that the accrued sample size as well as effect size were sufficiently large to draw a solid conclusion, and the advantage of adrenalectomy over MRA was constant with the chronological sequence. Conclusions: In conclusion, adrenalectomy could be preferred over MRA for patients with PA in reducing the risk of all-cause mortality and/or MACE and should be considered as the treatment of choice. That patients with PA could get less benefit from adrenalectomy as they age warrants further investigation.

With a 5-year survival rate of less than 50%, ovarian high-grade serous carcinoma (HGSC) is one of the most highly aggressive gynecological malignancies affecting women today. The high mortality rate of HGSC is largely attributable to delays in diagnosis, as most patients remain undiagnosed until the late stages of -disease. There are currently no recommended screening tests for ovarian cancer and there thus remains an urgent need for new diagnostic methods, particularly those that can detect the disease at early stages when clinical intervention remains effective. While diagnostics for ovarian cancer share many of the same technical hurdles as for other cancer types, the low prevalence of the disease in the general population, coupled with a notable lack of sensitive and specific biomarkers, have made the development of a clinically useful screening strategy particularly challenging. Here, we present a detailed review of the overall landscape of ovarian cancer diagnostics, with emphasis on emerging methods that employ novel protein, genetic, epigenetic and imaging-based biomarkers and/or advanced diagnostic technologies for the noninvasive detection of HGSC, particularly in women at high risk due to germline mutations such as BRCA1/2. Lastly, we discuss the translational potential of these approaches for achieving a clinically implementable solution for screening and diagnostics of early-stage ovarian cancer as a means of ultimately improving patient outcomes in both the general and high-risk populations.

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