BackgroundNephrotoxicity is a major hazard complicating the use of platinum based drugs (PBD), which can hinder using higher doses protocols to maximize the therapeutic gain. Shortage of serum creatinine level as an accurate biomarker for acute kidney injuries (AKI) necessitates searching for novel biomarkers with better sensitivity and specificity in patients on PBD.MethodsIn a prospective cohort design, 132 patients receiving PBD were selected for the study. AKI was diagnosed by continuous follow up of serum creatinine level according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines 2012. Serum creatinine and urinary biomarkers (KIM-1, NGAL and cystatin C) was measured in the day of treatment and for 3 days after PBD cycle.ResultsAKI occurred in 35 patients (26.52% of patients). KIM-1, Cystatin C, and NGAL showed significant increase in samples collected in the day of AKI in comparison to their corresponding basal levels (P <  0.0001). In addition, significant increase in urinary levels of the biomarkers in samples collected 1 day before AKI in comparison to their basal levels (P <  0.0001, P <  0.0001, and P = 0.013 for KIM-1, NGAL and Cystatin C respectively). Furthermore KIM-1 data showed a significant increase 2 days before serum creatinine rise in comparison to the corresponding KIM-1 levels in patients who developed AKI (P = 0.001).ConclusionsUrinary KIM-1, Cystatin C and NGAL can predict PBD induced AKI in earlier stages than serum createnine. KIM-1 is the most sensitive biomarker for early detection of AKI in patients receiving PBD.

Background: Lung cancer is one of the most frequently diagnosed malignancies. Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a recently discovered ligand of the B7 family. Blocking this immune checkpoint has become an important treatment option for lung cancer. Methods: The study includes 62 biopsy specimens either bronchoscopic or CT-guided biopsies diagnosed as lung cancer in Hospitals of Faculty of Medicine, Mansoura University, Egypt during the period from 2016 to 2020. Immunohistochemical Staining for HHLA2 and EGFR was performed. HHLA2 expression was assessed in different pathological types of lung Cancer, and it was correlated with other clinicopathologic parameters and patient prognosis. Results: We found a significant association between HHLA2 expression and metastasis. About 83% of patients presented with metastasis showed positive expression of HHLA2 compared to 44.4% in patients with no metastasis (p=0.02). Also, results show significant mild positive correlation between expression of HHLA2 and EGFR markers (p=0.045). The mean OS time in cases with positive HHLA2 expression was nearly half that of patients with negative expression of the markers. However, this difference was not statistically significant. But, PFS of patients was significantly lower among the group with positive expression of HHLA2 compared to the group with negative expression of HHLA2 (p= 0.01). Conclusions: This study reports that recently discovered, HHLA2 is over expressed in lung cancer associating with higher stage. It is also correlated with EGFR overexpression. HHLA2 could serve as a predictor of progression and distant metastasis. Also, it has potential to be effective immune target in lung cancer immunotherapy such as checkpoint blockade and antibody-drug conjugate treatment.

Background Acute-on-chronic liver failure (ACLF) is a distinct syndrome associated with high short-term mortality. Early identification of patients at high risk is essential to determine emergency for transplantation and decide and prioritize the need for intensive care unit (ICU). We aimed to evaluate the performance of the different prognostic scores in the prediction of in-hospital mortality in patients with ACLF. A total of 249 patients with ACLF were included and followed till discharge from the hospital. Univariate and Cox regression analyses were used to assess the performance of liver-specific (Child-Pugh and MELD) and ACLF prognostic scores (CLIF-C OF, CLIF-SOFA, CLIF-C AD, CLIF-C ACLF) in the prediction of in-hospital mortality. Results Patients were mostly males (71.1%) with a mean age of 53.9 ± 12.8 years. The etiology of pre-existing liver disease was HCV in 57.8%. Sepsis was the most common precipitating factor (49.8%) and the mortality rate was 74.3%. In univariate analysis, all scores were significantly higher in the deceased group (P<0.0001). AUROC were 0.897, 0.884, 0.870, 0.861, 0.861, and 0.850 for CLIF-C OF, CLIF-C AD, CLIF-C ACLF, Child-Pugh, CLIF-SOFA, and MELD scores, respectively. In multivariate analysis, 2 independent predictors of mortality were identified: CLIF-C ACLF score (OR 3.25, 95% CI 1.03–10.25, P<0.0001) and Child-Pugh class C (OR 1.04, 95% CI 1.02–1.06, P=0.044). Conclusions All the studied scores could predict in-hospital mortality of patients with ACLF. However, CLIF-C ACLF and Child-Pugh class performed better as they could significantly and independently predict mortality.

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