The Role of Predictive Models in the Assessment of the Poor Outcomes in Pediatric Acute Liver Failure

Objectives: In children, acute liver failure (ALF) is a severe condition with high mortality. As some patients need liver transplantation (LT), it is essential to predict the fatal evolution and to refer them early for LT if needed. Our study aimed to evaluate the prognostic criteria and scores for assessing the outcome in children with ALF. Methods: Data of 161 children with ALF (54.66% female, mean age 7.66 ± 6.18 years) were analyzed based on final evolution (32.91% with fatal evolution or LT) and etiology. We calculated on the first day of hospitalization the PELD score (109 children), MELD, and MELD-Na score (52 children), and King’s College Criteria (KCC) for all patients. The Nazer prognostic index and Wilson index for predicting mortality were calculated for nine patients with ALF in Wilson’s disease (WD). Results: PELD, MELD, and MELD-Na scores were significantly higher in patients with fatal evolution (21.04 ± 13.28 vs. 13.99 ± 10.07, p = 0.0023; 36.20 ± 19.51 vs. 20.08 ± 8.57, p < 0.0001; and 33.07 ± 8.29 vs. 20.08 ± 8.47, p < 0.0001, respectively). Moreover, age, bilirubin, albumin, INR, and hemoglobin significantly differed in children with fatal evolution. Function to etiology, PELD, MELD, MELD-Na, and KCC accurately predicted fatal evolution in toxic ALF (25.33 vs. 9.90, p = 0.0032; 37.29 vs. 18.79, p < 0.0001; 34.29 vs. 19.24, p = 0.0002, respectively; with positive predicting value 100%, negative predicting value 88.52%, and accuracy 89.23% for King’s College criteria). The Wilson index for predicting mortality had an excellent predictive strength (100% sensibility and specificity), better than the Nazer prognostic index. Conclusions: Prognostic scores may be used to predict the fatal evolution of ALF in children in correlation with other parameters or criteria. Early estimation of the outcome of ALF is essential, mainly in countries where emergency LT is problematic, as the transfer to a specialized center could be delayed, affecting survival chances.

FREQUENCY OF COMMON FACTORS INFLUENCING THE GRAFT UPTAKE IN MYRINGOPLASTY AMONG THE TERTIARY CARE HOSPITAL KPK

Introduction: Tympanoplasty refers to any operation involving reconstruction of the tympanic membrane and /or the ossicular chain. Myringoplasty is a tympanoplasty without ossicular reconstruction. Over the years many methods have been used for closing perforations. Myringoplasty was introduced by Berthold in 1878 but the modern era began only in 1950s with the work of Wullstein and Zoellner. The study aims to analyse the common factors which are predictive of success of myringoplasty in adult patients and to construct and validate a prognostic index that could be used as tool to predict the success of myringoplasty in adults. Objectives: To determine the frequency of common factors influencing the graft uptake in myringoplasty. Materials and Method: In this study, a total sample size was 376, using 4.08% proportion of fourth degree perineal tear, 95% confidence level and 2% margin of error under WHO software for sample size determination. Moreover, consecutive non probability sampling technique was used. Results: The mean age was 40 years with standard deviation of ± 2.63. Sixty two percent of the patients were male while thirty eight percent patients were female. The success rate of myringoplasty was 90% while the failure rate was 15(10%) patients in which 4(25%) patients had medium perforation, 5(33%) patients had large perforation while 6(42%) patients had subtotal perforation. Regarding the causes of perforation among 15(10%) patients, 13(85%) patients had infection while only 2 patients had trauma. Conclusion: The study concludes that infection (85%) was the most common cause of perforation followed by trauma (15%) in the graft uptake in myringoplasty.

Follicular lymphoma grade 3B and diffuse large B-cell lymphoma present a histopathological and molecular continuum lacking features of progression/transformation

The sole distinguishing feature of follicular lymphoma grade 3B and diffuse large B-cell lymphoma is the growth pattern assessed by histopathology analysis. Diffuse growth defines diffuse large B-cell lymphoma but the clinical relevance of this finding when occurring in follicular lymphoma grade 3B is uncertain. To address this question, individual and coexisting follicular lymphoma grade 3B and diffuse large B-cell lymphoma were separated and analyzed for immunophenotype and molecular genetic features by fluorescence in situ hybridization, targeted sequencing and gene expression profiling. Clinical features of follicular lymphoma grade 3B with and without coexisting diffuse large B-cell lymphoma were studied in homogeneously treated patients from a prospective randomized trial. Follicular lymphoma grade 3B and diffuse large B-cell lymphoma frequently show intermediate growth pattern and/or occurred simultaneously in the same tissue at the time of initial diagnosis. When occurring simultaneously follicular lymphoma grade 3B and diffuse large B-cell lymphoma do not differ significantly in genetic aberrations or phenotype but distinct features in gene expression reflect divergent microenvironment. Follicular lymphoma grade 3B with and without coexisting diffuse large B-cell lymphoma do not differ in major clinical parameters such as international prognostic index, response to immunochemotherapy, progression or overall survival. Follicular lymphoma grade 3B and simultaneous diffuse large B-cell lymphoma are molecularly homogenous. Histological detection of diffuse large B-cell lymphoma is not associated with features of a more aggressive disease and does not reflect transformation or progression of follicular lymphoma Grade 3B.

Pretreatment C-reactive Protein to Albumin Ratio Predicts Clinical Outcomes in Patients with Peripheral T-cell Lymphoma

Peripheral T-cell lymphoma (PTCL) is an aggressive and heterogenous T-cell lymphoid malignancy. The prognostic value of C-reactive protein-to-albumin ratio (CAR) has never been assessed in PTCL. This study retrospectively reviewed the medical records of 76 patients diagnosed with various subtypes of PTCL. The value of 0.794 was identified as the most discriminative point of CAR, and clinical outcomes, including response rate, overall survival (OS), and progression-free survival (PFS), were compared between the high (>0.794, n=25) and low (≤0.794, n=51) CAR groups. After induction therapy, complete response was achieved in 39 patients (76.5%) and 8 patients (32.0%) in the low and high CAR groups, respectively (p<0.001). During the median follow-up of 57.5 months, the high CAR group had significantly worse 5-year PFS (6.6% vs. 43.8%, p<0.0001) and 5-year OS (20.2% vs. 62.2%, p<0.0001) rates. With adjustment for the International Prognostic Index (≥3), Prognostic Index for PTCL-unspecified (≥3), and T cell score (≥2), high CAR remained a significant prognostic factor for PFS (hazard ratio [HR]: 4.01, 95% confidence interval [CI] 2.04–7.86, p<0.001) and OS (HR: 2.97, 95% CI: 1.33–6.64, p=0.008). CAR might play a complementary role in predicting prognosis in patients with PTCL, considering its simplicity, objectivity, and easy accessibility.

A Gene Prognostic Index Associated With Epithelial-Mesenchymal Transition Predicting Biochemical Recurrence and Tumor Chemoresistance for Prostate Cancer

BackgroundWe aimed to establish a novel epithelial-mesenchymal transition (EMT)-related gene prognostic index (EMTGPI) associated with biochemical recurrence (BCR) and drug resistance for prostate cancer (PCa).MethodsWe used Lasso and Cox regression analysis to establish the EMTGPI. All analyses were conducted with R version 3.6.3 and its suitable packages.ResultsWe established the EMTGPI based on SFRP4 and SPP1. Patients in high-risk group had 2.23 times of BCR risk than those in low-risk group (p = 0.003), as well as 2.36 times of metastasis risk (p = 0.053). In external validation, we detected similar diagnostic efficacy and prognostic value in terms of BCR free survival. For drug resistance, we observe moderately diagnostic accuracy of EMTGPI score (AUC: 0.804). We found that PDCD1LG2 (p = 0.04) and CD96 (p = 0.01) expressed higher in BCR patients compared with their counterpart. For TME analysis, we detected that CD8+ T cells and M1 macrophages expressed higher in BCR group. Moreover, stromal score (p = 0.003), immune score (p = 0.01), and estimate score (p = 0.003) were higher in BCR patients. We found that EMTGPI was significantly related to HAVCR2 (r: 0.34), CD96 (r: 0.26), CD47 (r: 0.22), KIR3DL1 (r: −0.21), KLRD1 (r: −0.21), and CD2 (r: 0.21). In addition, we observed that EMTGPI was significantly associated with M1 macrophages (r: 0.6), M2 macrophages (r: −0.33), monocytes (r: −0.18), neutrophils (r: −0.43), CD8+ T cells (r: 0.13), and dendritic cells (r: 0.37). PHA-793887 was the common drug sensitive to SPP1 and SFRP4, and PC3 and DU145 were the common PCa-related cell lines of SPP1, SFRP4, and PHA-793887.ConclusionsWe concluded that the EMTGPI score based on SFRP4 and SPP1 could be used to predict BCR for PCa patients. We confirmed the impact of immune evasion on the BCR process of PCa.

A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study

Background Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. Methods We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan–Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. Results and conclusions Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell’s concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.