Independent Predictor Of Treatment Outcome Research Articles

INFLUENCE OF DURATION OF UNTREATED PSYCHOSIS ON THE SHORT-TERM OUTCOME IN FIRST-EPISODE SCHIZOPHRENIA

Objectives: Schizophrenia is a devastating disease and many patients present late for treatment due to difficulty in identifying symptoms by family members. The objective of this study is to find if there is an association between a longer duration of untreated psychosis (DUP) and poor treatment outcome in first-episode Schizophrenics and to find if there is an association between premorbid social adjustment on DUP. Methods: Anti-psychotic-naïve patients with an international classification of diseases-10 schizophrenia were evaluated 12 weeks after their first in-patient hospitalization. Association between untreated initial psychosis duration (measured from the beginning of first symptom as well as from first hospital admission) was examined by conducting the clinical interview, symptom severity by positive and negative syndrome scale, and clinical global impression scale, pre-morbid social adjustment by premorbid social adjustment (PSA) scale; and symptoms improvement after treatment by CGI-I scale. Results: Of the 57 patients studied, 57.9% showed improvement after treatment, paranoid type was more common, patients responded better when treated with combined typical and atypical antipsychotics and improvement was better when DUP was <2 years. There was a major negative correlation between positive syndrome scores and DUP. There was no association of DUP with negative syndrome score, psychopathology score and PSA score. Conclusion: DUP was an independent predictor of treatment outcome and early intervention is necessary for better prognosis.

THE SIGNIFICANCE OF MINIMAL RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC LEUKAEMIA: A SINGLE CENTRE STUDY

In Acute lymphoblastic Leukemia (ALL) assessment of molecular response to treatment, assessing minimal residual disease (MRD) is a major independent predictor of treatment outcome. Consequently, MRD is implemented in all ALL-treatment protocols to fill up or to redefine stratification of multifactorial risk with optional intensity of customized treatment. Aim: to specify the significance of MRD in the assessment of remission in children with ALL with results discordant between morphology and flow cytometry at the end of induction phase of therapy. Materials and Methods: A descriptive cross-sectional study was conducted at Jin Oncology Center from March 2019 through November 2023. Data were taken out of the records of 58 patients who had ALL less than 16 years old. All patients were less than 16 years old and treated by ukall. They were diagnosed using peripheral blood morphology, bone marrow study and/or flow cytometry when lymphoblasts in peripheral blood or bone marrow aspirate are ≥20% and was confirmed by flow cytometry. On 29th day of induction therapy, bone marrow was examined for morphology and flow cytometry. The presence or absence of MRD was determined, and CD19, CD10 and tdt were tested. By morphologic assessment they were divided patients into: Category 1, C1 (<5% blasts), Category 2, C2 (5-20% blasts), and Category 3, C3 (>20% blasts). Statistical analysis was made using SPSS version 25. P value of less than 0.05 was considered significant. Results: The study involved 58 patients who had ALL. with a median age of 6.5 years, male to females ratio of 1.76:1, mean platelet count of 96.6 x 10⁹/L ,mean hemoglobin of 8.6 g/dL, mean leucocyte count of 74.3 x 10⁹/L), 48 cases (82.7%) of B-cell lineage and 10 cases (17.3%) of T-cell lineage, 94.6% of the B-cell cases were of the common B-ALL and the rest Pro-BALL type, 54.6% of the T-cell ALL was cortical T-ALL and 44.4% Early T-cell ALL. They were tested for MRD by morphology and flow cytometry on day 29. By morphology, 46 patients had remission but by flow only 24 cases. Seventeen cases had residual blasts >5%. In 19 cases there was a discrepancy between the results of morphology and flow. Twenty-five cases (52.08% of B-cell cases) were positive for MRD by flow results. Eight of the ten cases of T-ALL (80%), were positive for MRD by flow cytometry. Among 48 cases of B-ALL, 36 were in C1 category (morphologically in remission), 11 cases were in C2 category and one case in the C3 category. Of cases in C1 category, 17 were MRD +ve and 19 were MRD –ve by flow cytometry. In the C2 category, only 2 out of the 11 cases (18.18%) had discordant results between morphology and flow results. The correlation between morphology and flow results was 100% in the C3 category. Conclusion: MRD should not be the surrogate of morphology but to be used in conjunction in order to give us a more accurate representation of status of remission.

Salivary pepsin as an independent predictor of treatment response for laryngopharyngeal reflux: prospective cohort study with multivariate analysis

To analyze the predictive value of salivary pepsin for treatment outcomes in laryngopharyngeal reflux (LPR) using multivariate analysis that includes various associated factors. This prospective cohort study was conducted between August 2020 and August 2022. Patients with LPR who had symptoms lasting more than 1 month and a reflux symptom index (RSI) of 14 or higher were enrolled. The participants received a 2-month regimen of proton pump inhibitors (PPIs) treatment and lifestyle modification. Salivary pepsin was checked using fasting saliva before treatment. Salivary pepsin was detected more frequently in the good treatment response group (61.1%), compared to 14.3% in the poor response group. Similarly, patients with higher compliance to lifestyle modifications (> 90%) had a higher chance of a good response (91.7%) compared to those with lower compliance, who had a 53.8% chance of a good response. Other clinical factors have no significant association with treatment response. In multivariate analysis, both pretreatment salivary pepsin and higher compliance with lifestyle modification were found to be independent factors for treatment response (OR 14.457, CI 1.075 ~ 194.37 for both). This study found that positive salivary pepsin and strict lifestyle modification are independent predictors of treatment outcomes in LPR.

Multicenter, Prospective Study to Investigate the Efficacy and Safety of Intravenous-Immunoglobulin Therapy in Elderly Patients with Diffuse Large B Cell Lymphoma Treated with R-Mini-CHOP

Background The median age at initial diagnosis of DLBCL is estimated to be between the ages of 60 and 70. The number of elderly patients with DLBCL is gradually increasing. But, treatment outcomes of elderly patients were not significantly improved compared to younger patients. Infection is an independent predictor of treatment outcome in patients with DLBCL, and the risk of infection increases with age. The incidence of hypogammaglobulinemia in patients with malignant lymphoma increased from 15% to 39% after rituximab therapy. There was a significant decrease in the occurrence of major infections after intravenous immunoglobulins (IVIG) prophylaxis in hypogammaglobulinemia patients with lymphoproliferative. disorders. In this multicenter prospective study, infection prevention effect and treatment outcomes were identified using IVIG in elderly DLBCL patients with hypogammaglobulinemia who received rituximab combination chemotherapy. Methods In the current study, newly diagnosed DLBCL patients aged 70 years or older who were planning to receive R-mini-CHOP therapy were included. Patients with hypogammaglobulinemia at diagnosis were assigned to the IVIG group. Patients received R-mini-CHOP (rituximab: 375mg/m 2 D1; cyclophosphamide: 400mg/m 2 D1; doxorubicin: 25mg/m 2 D1; vincristine: 1.0mg D1, and prednisolone 40mg/m 2 from D1 to D5), and pegylated G-CSF. After the first cycle of R-mini-CHOP, 400mg/kg of IVIG was administered on D3 and D11. After the second cycle to sixth cycle of chemotherapy, patients received 400mg/kg of IVIG on D11. The primary objective was to evaluate the efficacy of IVIG in reducing severe infections. Grade 3 or 4 infections were defined as severe infections. Results A total of 118 elderly patients were newly diagnosed with DLBCL and were scheduled to receive R-mini-CHOP therapy. Hypogammaglobulinemia was identified in 85 (72.0%) patients. Decreased immunoglobulin D (n=42) and immunoglobulin M (n=39) level were most common, and 18 patients had two or more types of hypogammaglobulinemia at the same time. Fifty-six patients were assigned to the group receiving IVIG. Median age was 77 years (range, 70-90), and 31 (55.4%) were male. In patients who completed R-mini-CHOP and IVIG treatment, complete remission rate was 79.4%. Severe infections of grade 3 or 4 occurred in 3 of 56 (5.4%) patients, and only five (8.9%) patients had COVID-19 infection during the study period. Adverse effects associated with IVIG include fever/chilling, nausea/vomiting which were generally manageable. Only one patient discontinued the study because of chest pain that occurred during IVIG administration. In patients with hypogammaglobulinemia who did not receive IVIG, severe infections occurred in 8 of 29 (27.6%) patients, and COVID-19 infection was developed in 7 of 29 (24.1%). In patients without hypogammaglobulinemia, severe infection occurred in 5 of 33 (15.2%), and COVID-19 infection was developed in 8 of 33 (24.2%) patients. Patients receiving IVIG had a significantly reduced incidence of severe infection compared to patients not receiving IVIG (p=0.028). Furthermore, COVID-19 infection rate during R-mini-CHOP therapy was lower in IVIG receiving patients (p=0.050). Long-term outcomes with relapse rate and survival will be followed up and updated. Conclusion In elderly patients with DLBCL, the combination of R-mini-CHOP and IVIG was safe and effective in preventing infection. In the COVID-19 era, the combination of chemotherapy and IVIG should be considered in elderly DLBCL patients to reduce infection rate and improve treatment outcomes.

The Pattern of Initial Presentation of Diabetes, Treatment Outcome and Its Predictors Among Diabetic Pediatrics Attended Service at Selected Public Hospitals of Southern Ethiopia: A Multi-Center Study.

Diabetes mellitus is the most common metabolic disorder in the pediatric population. Globally the incidence of diabetes increased from 11.3 million (95% UI 10.6-12.1) in 1990 to 22.9 million (21.1-25.4) in 2017, with a 102.9% increase and there was a 3% increase in diabetes mortality rates by age between 2000 and 2019. This study aims to assess the pattern of initial presentation of pediatric diabetes mellitus, treatment outcome, and its predictors among pediatrics who attended service at selected public hospitals in southern Ethiopia from 2015 to 2019. A cross-sectional study was conducted among 422 randomly selected pediatrics from October 1st, 2021 to December 30, 2021, and participants were selected randomly from 8 randomly selected public hospitals in southern Ethiopia after proportional to client flow allocation of samples. Data was extracted from clients' charts using a data extraction checklist. Statistical Package for Social Sciences (SPSS) version 24, and logistic regression analysis were applied to determine the presence of an association between dependent and independent variables, and significance was declared at p-value <0.05. In this study, most (74.6%) of the pediatrics initially presented with Diabetic ketoacidosis (DKA). This study found that Two-thirds (67.1%) of the respondents in the study had a good treatment outcome. In this study residence, presenting signs and symptoms; poly symptoms and weight loss, history of hospitalization, and comorbidity were predictors of treatment outcome of pediatric diabetes mellitus. Diabetes mellitus with Diabetic ketoacidosis is the predominant pattern of initial presentation in the study. The magnitude of poor treatment outcomes of diabetes mellitus among pediatrics in this study is high and unacceptable Residence, signs, and symptoms at initial presentation, history of hospitalization, and comorbidity were found to be significant independent predictors of treatment outcome of pediatric diabetes mellitus.

Utilizing the Systemic Immune-Inflammation Index and Blood-Based Biomarkers in Association with Treatment Responsiveness amongst Patients with Treatment-Resistant Bipolar Depression.

(1) Background: Inflammation is associated with depressive illness and treatment resistance. This study assessed a novel inflammatory index, the Systemic Immune-Inflammation Index (SII), in patients diagnosed with treatment-resistant bipolar depression (TRBDD) before and after treatment with escitalopram (ESC) and celecoxib (CBX) add-on or ESC and placebo (PBO), and compared them to healthy control (HC) subjects. (2) Methods: This is a secondary biological analysis from a double-blind randomized placebo-controlled trial of CBX augmentation in TRBDD. Our subsample with available complete blood count (CBC) data included 52 TRBDD subjects, randomized into an ESC + CBX, (n = 29), an ESC + PBO arm (n = 23), and an HC group (n = 32). SII was calculated from the CBC with differential (SII = platelets x neutrophils/lymphocytes) at baseline and end of treatment (8 weeks). Blood inflammation biomarkers, growth factors, and kynurenine metabolites were determined at both timepoints. Depressive symptom severity was the primary outcome, using the HAMD-17 rating scale score to quantitate treatment response and remission rates. (3) Results: Baseline SII did not discriminate TRBDD from HC, nor was it associated with HAMD-17 score at any timepoint, although it was significantly associated with lower baseline VEGF (p = 0.011) and higher week 8 levels of IL1-β (p = 0.03) and CRP (p = 0.048). Post-treatment HAMD-17 was not independently predicted using baseline SII unless an interaction with age was present (p = 0.003 was included), even after relevant adjustments. A similar effect was seen with baseline neutrophils. (4) Conclusions: While SII was not an independent predictor of treatment outcome, elevated baseline SII was a predictor of poor treatment response amongst older patients with TRBDD.

QUANTITATIVE WHOLE‐BODY MRI FOR PREDICTING TREATMENT OUTCOME IN PEDIATRIC PATIENTS WITH AGGRESSIVE NON‐HODGKIN LYMPHOMA UNDERGOING CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY

Introduction: Chimeric antigen receptor (CAR) T cell therapy has shown great promise in treating pediatric patients with aggressive non-Hodgkin lymphoma (NHL), but its effectiveness can vary greatly among individuals. Accurate prediction of treatment response can aid in patient selection and treatment planning. Quantitative whole-body diffusion-weighted MRI (WB-DW MRI) has emerged as a potential tool for predicting treatment response in various types of cancer, but its predictive value for CAR-T cell therapy in pediatric patients with aggressive NHL has not been fully explored. This prospective multicenter study aimed to investigate the predictive value of quantitative whole-body diffusion-weighted MRI in this patient population. Methods: Thirty-six pediatric patients with aggressive NHL who underwent CAR T cell therapy were enrolled from three participating centers. All patients underwent WB-DW MRI before and after CAR T cell therapy. T2 values, apparent diffusion coefficient (ADC) values, and the ADC change between baseline and within 15 days after infusion were calculated. Patients were categorized into good outcome (complete remission) and poor outcome (progressive or recurrent disease) groups based on their treatment response. Receiver operating characteristic (ROC) curve analysis was used to evaluate the correlation between ADC values and treatment outcome. Results: The mean age of patients was 11 years, with 31 males. The mean change in ADC value between baseline and within 15 days after infusion was significantly higher in the good outcome group compared to the poor outcome group (p < 0.01). The change in ADC value was an independent predictor of treatment outcome on logistic regression analysis after adjusting for age, gender, and disease stage (odds ratio: 1.017; 95% confidence interval: 1.003–1.030; p < 0.01). The area under the ROC curve for ADC change was 0.794 (95% confidence interval: 0.649–0.939). Keywords: cellular therapies, immunotherapy, Imaging and Early Detection - Other No conflicts of interests pertinent to the abstract.

Metabolic syndrome is independently associated with improved overall survival to first-line therapy with immune checkpoint inhibitors in non-small cell lung cancer.

Many co-existing medical conditions may affect the outcome in patients treated with immune checkpoint inhibitors for advanced cancer. There is currently not any information on whether metabolic syndrome (MetS) impacts the clinical outcome in patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell line cancer (NSCLC). We carried out a single-center retrospective cohort study to determine the effects of MetS on first-line ICI therapy in patients with NSCLC. One hundred and eighteen consecutive adult patients who received first-line therapy with ICIs and had adequate medical record information for the determination of MetS status and clinical outcomes were included in the study. Twenty-one patients had MetS and 97 did not. There was no significant difference between the two groups in age, gender, smoking history, ECOG performance status, tumor histologic types, pre-therapy use of broad-spectrum antimicrobials, PD-L1 expression, pre-treatment neutrophil:lymphocyte ratio, or proportions of patients who received ICI monotherapy or chemoimmunotherapy. With a median follow-up of 9 months (range 0.5-67), MetS patients enjoyed significantly longer overall survival (HR 0.54, 95% CI: 0.31-0.92) (p = 0.02) but not progression-free survival. The improved outcome was only observed in patients who received ICI monotherapy and not chemoimmunotherapy. MetS predicted for higher probability of survival at 6 months (p = 0.043) and 12 months (p = 0.008). Multivariate analysis indicated that, in addition to the known adverse effects of use of broad-spectrum antimicrobials and the beneficial effects of PD-L1 (Programmed cell death-ligand 1) expression, MetS was independently associated with improved overall survival but not progression-free survival. Our results suggest that MetS is an independent predictor of treatment outcome in patients who received first-line ICI monotherapy for NSCLC.

Participant- and Disease-Related Factors as Independent Predictors of Treatment Outcomes in the RESTORE-IMI 2 Clinical Trial: A Multivariable Regression Analysis.

In the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was noninferior to piperacillin/tazobactam in treating hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia. This post hoc analysis was conducted to determine independent predictors of efficacy outcomes in the RESTORE-IMI 2 trial, to assist in treatment decision making. A stepwise multivariable regression analysis was conducted to identify variables that were independently associated with day 28 all-cause mortality (ACM), favorable clinical response at early follow-up (EFU), and favorable microbiologic response at end of treatment (EOT). The analysis accounted for the number of baseline infecting pathogens and in vitro susceptibility to randomized treatment. Vasopressor use, renal impairment, bacteremia at baseline, and Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II scores ≥15 were associated with a greater risk of day 28 ACM. A favorable clinical response at EFU was associated with normal renal function, an APACHE II score <15, no vasopressor use, and no bacteremia at baseline. At EOT, a favorable microbiologic response was associated with IMI/REL treatment, normal renal function, no vasopressor use, nonventilated pneumonia at baseline, intensive care unit admission at randomization, monomicrobial infections at baseline, and absence of Acinetobacter calcoaceticus-baumannii complex at baseline. These factors remained significant after accounting for polymicrobial infection and in vitro susceptibility to assigned treatment. This analysis, which accounted for baseline pathogen susceptibility, validated well-recognized patient- and disease-related factors as independent predictors of clinical outcomes. These results lend further support to the noninferiority of IMI/REL to piperacillin/tazobactam and suggests that pathogen eradication may be more likely with IMI/REL. NCT02493764.

Comparative analysis of outcome predictors in patients with postoperative peritonitis depending on the method of surgical treatment – relaparotomy on demand vs vacuum-assisted laparostomy

Background: Secondary postoperative diffuse peritonitis (SPDP) is one of the most severe complications of elective and emergency surgical interventions associated with a high mortality rate. To date, no optimal tactics of surgical treatment of SPDP has been developed.Objective: The analysis of independent predictors of outcome depending on the method of surgical treatment – relaparotomy ondemand (RD) or vacuum-assisted laparostomy (VAL).Material and methods: The study included 141 adult patients, male and female in the period from January 2014 to December 2020: group I (n = 63) – patients who received VAL method; group II (n = 78) – RD method. The method of multivariate logistic regression analysis was used to calculate the independent effects of potential predictor variables on the treatment outcome.Results: The following independent predictors of treatment outcome in the RD group were identified: age, duration of hospital stay, number of relaparotomies, APACHE II score, Björck classification grade 1C at the 1st sanitation, bacteremia, Clavien–Dindo complications class 3a and 4a. For the VAL group: conversion of surgical tactics and bacteremia.Conclusion: In patients with SPDP in the presence of risk factors for unfavorable outcomes, the use of VAL with staged sanitation of the abdominal cavity is indicated.

Tumour response heterogeneity as a powerful independent predictor of treatment outcome in advanced lung adenocarcinoma: a retrospective analysis

Tumour response heterogeneity to treatment is common across different foci in the same patient with cancer. However, the effect of heterogeneity on clinical outcome remains unclear. Here, we developed a quantitative assessment of tumour response heterogeneity and explored the correlation of tumour response heterogeneity with the clinical outcome. Patients eligible for this retrospective study had advanced lung adenocarcinoma, with 3-10 measured foci, an Eastern Cooperative Oncology Group status of 0-1, and received first-line chemotherapy or targeted therapy. Percent change of the longest diameter in each measurable lesion were assessed as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The tumour response heterogeneity score was the absolute value of the dispersion coefficient of the percentage value of each target lesion. Patients were randomly divided (1:1) into a learning and a validation set. The optimal cutoff value of tumour response heterogeneity score was identified according to progression-free survival information in the discovery cohort. We then confirmed and analysed the correlation of tumour response heterogeneity scores with clinicopathological features in the validation cohort. Next-generation sequencing was used to investigate a potential mechanism linking tumour response heterogeneity scores to clinical outcomes. Data from 174 patients were collected between Jan 1, 2016, and Dec 30, 2020. 101 (58%) patients had been treated with platinum-based doublet chemotherapy and 73 (42%) with targeted therapy. Median follow-up was 19·8 months (IQR 3·71-13·75). In the discovery cohort (n=85), the optimal cutoff point of tumour response heterogeneity score was defined as 0·46. Patients with high tumour response heterogeneity score had worse progression-free survival than patients with low tumour response heterogeneity (median 4·5 months [95% CI 3·6-8·6] vs 15·8 months (12·8-not reached), hazard ratio [HR] 4·43 [95% CI 2·14-9·16]; p<0·0001). In the validation cohort (n=89), high tumour response heterogeneity score was shown to be associated with significantly shorter progression-free survival (median 5·1 months (95% CI 3·5-7·8) vs 12·9 months (10·4-28·7), HR 2·69 [95% CI 1·59-4·55]; p<0·0001). The median value of tumour response heterogeneity score followed the order of progressive disease, stable disease, and partial response (p<0·0001). Patients with high tumour response heterogeneity score had worse overall response rate than patients with low tumour response heterogeneity score (30·0% vs 68·0%; Fisher's exact test p<0·0001). In the overall population (n=174), high tumour response heterogeneity score was further shown to be an independent biomarker for progression-free survival by univariate and multivariate analysis. Moreover, tumour response heterogeneity score was able to further distinguish the outcomes in partial response and stable disease subgroup. In the partial response group, high tumour response heterogeneity score was associated with significantly shorter progression-free survival in the partial response subgroup (HR 2·79 [95% CI 1·24-6·29; p=0·0006) and the stable disease subgroup (HR 2·55 [95% CI 1·44-4·49]; p=0·0015). Compared with low tumour response heterogeneity score, high tumour response heterogeneity score was associated with higher tumour mutation burden and high frequency variation of cell cycle signal pathway. The tumour response heterogeneity score, a novel metric for tumour response heterogeneity, was a powerful independent predictor of outcome in advanced lung adenocarcinoma. The tumour response heterogeneity score further stratified patients with the same RECIST assessment results and could be a useful addition to the RECIST assessment system. Further prospective studies are warranted. National Natural Science Foundation of China (grant 82072565) and Bejing Xisike Clinical Oncology Research Foundation (grant Y-2019AZZD-0386).

Tumor response heterogeneity, a powerful independent predictor of treatment outcome in advanced lung adenocarcinoma.

e21146 Background: Tumor response heterogeneity (TRH) to treatment is common across different foci within the same cancer patient. However, the effect of heterogeneity on clinical outcome remains unclear. Here, we developed a quantitative assessment of TRH and explored the correlation of TRH with the clinical outcome. Methods: In this retrospective study, the main eligibility criteria were: patients with advanced lung adenocarcinoma, 3-10 measured foci, ECOG 0-1 and received first-line chemotherapy or targeted therapy. Percent change of the longest diameter in each measurable lesion were quantified with RECIST1.1. TRH score was the absolute value of the dispersion coefficient of the percentage value of each target lesion. Patients were randomly divided into a learning and a validation set. The optimal cutoff value of TRH score was identified according to progression free survival information in the discovery cohort. Then, we confirmed and analyzed the correlation of TRH scores with clinicopathological features in the validation cohort. The Next-generation sequencing was performed for mechanism exploration. Results: Between January 2016 and December 2020, 174 patients were enrolled, 101 (58.0%) treated with platinum-based doublet chemotherapy and 73 (42.0%) with targeted therapy. Median follow-up was 19.8 months (95% CI, 14.5 to 25.0). In the discovery cohort (n = 85), 0.46 was defined as the optimal cut-off point of TRH score. Patients with high TRH score had poor PFS (median PFS 4.5 months vs. 15.8 months, HR 4.43; 95% CI 2.14 to 9.16; P &lt; 0.001) compared to those with low TRH score. In validation cohort (n = 89), high TRH score was confirmed to be associated with significantly shorter PFS (median PFS 5.1 months vs. 12.9 months, HR 2.69; 95% CI 1.59 to 4.55; P &lt; 0.001). The median value of TRH score followed the order of PD, SD and PR ( P &lt; 0.001). Patients with high TRH score had poor ORR (30.0% vs. 68.0%; Fisher's exact test, P &lt; 0.001) compared with those with low TRH score. In all population, high TRH score was further confirmed as an independent biomarker for PFS by univariate and multivariate analysis. Moreover, TRH score were able to further distinguish the outcomes in PR and SD subgroup. In PR, high TRH score was associated with significantly shorter PFS in PR subgroup (HR 2.79; 95% CI 1.24 to 6.29; P &lt; 0.001) and SD subgroup (HR 2.55; 95% CI 1.44 to 4.49; P = 0.002), respectively. Compared with low TRH score, high TRH score was associated with higher tumor mutation burden and high frequency variation of cell cycle signal pathway. Conclusions: TRH score, a novel parameter for evaluating tumor response heterogeneity, was a powerful independent predictor of outcome in advanced lung adenocarcinoma. The TRHscore further stratifies patients with the same RECIST assessment results and is a useful addition to the RECIST assessment system. Further prospective studies are warranted.

Прогностички фактори кај детската акутна лимфобластна леукемија- преглед на литература

Во последните неколку декади е остварен значаен напредок во терапискиот исход кај детската акутна лимфобластна леукемија (АЛЛ), што резултира со денешно 5-годишно вкупно преживување кое достигнува до 90%. Овој импресивен успех се должи на примената на ефикасни, комбинирани хемотераписки режими и прецизна стратификација на пациентите во ризични групи според добро дефинирани прогностички фактори кои ги вклучуваат клиничките карактеристики присутни при дијагнозата, биолошките и генетските карактеристики на леукемиските клетки и раниот одговор на терапија. Пациентите кои се класифицираат во прогностичка група со низок ризик се третираат со помалку интензивна терапија, додека за тие со високо-ризични карактеристики се применуваат поагресивни режими. Минималната резидуална болест (МРБ) во моментов претставува најважен и независен предиктор на терапискиот исход. Во овој ревијален труд се опишани клиничките, биолошките карактеристики и раниот одговор на терапија како и актуелните сознанија кои ја поддржуваат нивната клиничка примена кај детската АЛЛ.

1574. Multivariate Regression Analysis to Determine Independent Predictors of Treatment Outcomes in the RESTORE-IMI 2 Trial

BackgroundIn the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was non-inferior to PIP/TAZ for treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in the primary endpoint of Day 28 all-cause mortality (D28 ACM) and the key secondary endpoint of clinical response (CR) at early follow-up (EFU; 7-14 d after end of therapy). We performed a multivariate regression analysis to determine independent predictors of treatment outcomes in this trial.MethodsRandomized, controlled, double-blind, phase 3, non-inferiority trial comparing IMI/REL 500 mg/250 mg vs PIP/TAZ 4 g/500 mg, every 6 h for 7-14 d, in adult patients (pts) with HABP/VABP. Stepwise-selection logistic regression modeling was used to determine independent predictors of D28 ACM and favorable CR at EFU, in the MITT population (randomized pts with ≥1 dose of study drug, except pts with only gram-positive cocci at baseline). Baseline variables (n=19) were pre-selected as candidates for inclusion (Table 1), based on clinical relevance. Variables were added to the model if significant (p < 0.05) and removed if their significance was reduced (p > 0.1) by addition of other variables.ResultsBaseline variables that met criteria for significant independent predictors of D28 ACM and CR at EFU in the final selected regression model are in Fig 1 and Fig 2, respectively. As expected, APACHE II score, renal impairment, elderly age, and mechanical ventilation were significant predictors for both outcomes. Bacteremia and P. aeruginosa as a causative pathogen were predictors of unfavorable CR, but not of D28 ACM. Geographic region and the hospital service unit a patient was admitted to were found to be significant predictors, likely explained by their collinearity with other variables. Treatment allocation (IMI/REL vs PIP/TAZ) was not a significant predictor for ACM or CR; this was not unexpected, since the trial showed non-inferiority of the two HABP/VABP therapies. No interactions between the significant predictors and treatment arm were observed.ConclusionThis analysis validated known predictors for mortality and clinical outcomes in pts with HABP/VABP and supports the main study results by showing no interactions between predictors and treatment arm.Table 1. Candidate baseline variables pre-selected for inclusion Figure 1. Independent predictors of greater Day 28 all-cause mortality (MITT population; N=531) Figure 2. Independent predictors of favorable clinical response at EFU (MITT population; N=531) DisclosuresRobert Tipping, MS, Merck & Co., Inc. (Employee, Shareholder) Jiejun Du, PhD, Merck & Co., Inc. (Employee, Shareholder) Maria C. Losada, BA, Merck & Co., Inc. (Employee, Shareholder) Michelle L. Brown, BS, Merck & Co., Inc. (Employee, Shareholder) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Joan R. Butterton, MD, Merck & Co., Inc. (Employee, Shareholder) Amanda Paschke, MD MSCE, Merck & Co., Inc. (Employee, Shareholder) Luke F. Chen, MBBS MPH MBA FRACP FSHEA FIDSA, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder)

Prognostic value of imaging markers from 18FDG-PET/CT in paediatric patients with Hodgkin lymphoma.

Identification of imaging prognostic parameters for early therapy personalisation to reduce treatment-related morbidity in paediatric Hodgkin lymphoma (HL). Our aim was to evaluate quantitative markers from baseline 2-[18F]fluoro-2-deoxy-d-glucose PET/CT as prognostic factors for treatment outcomes. Another goal was assessing the prognostic value of Deauville score at interim PET/CT. Twenty-one patients were prospectively enrolled. Median age was 12 years (range 6-17); 13 were female. Patients underwent PET/CT for disease staging (bPET), at the end of two cycles of chemotherapy (iPET) and after chemotherapy. A total of 173 lesions were segmented from bPET. We calculated 51 texture features for each lesion. Total metabolic tumour volume and total lesion glycolysis from bPET were calculated for response prediction at iPET. Univariate and multivariate analyses were used for optimal cut-off values to separate responders at iPET according to the Deauville score. We identified four texture features as possible independent predictors of treatment outcomes at iPET. The areas under the ROC for univariate analysis were 0.89 (95% CI, 0.75-1), 0.82 (95% CI, 0.64-1), 0.79 (95% CI, 0.59-0.99) and 0.89 (95% CI, 0.75-1). The survival curves for patients assigned Deauville scores 1, 2, 3 and X were different from those assigned a score 4, with 4-year progression free-survival (PFS) rates of 85 versus 29%, respectively (P = 0.05). We found four textural features as candidates for predicting early response to chemotherapy in paediatric patients with HL. The Deauville score at iPET was useful for differentiating PFS rates.

A predictive model for treatment response in patients with locally advanced esophageal squamous cell carcinoma after concurrent chemoradiotherapy: based on SUVmean and NLR

BackgroundWe conducted this study to combine the mean standardized uptake value (SUVmean) and neutrophil to lymphocyte ratio (NLR) to establish a strong predictive model for patients with esophageal squamous cell carcinoma (ESCC) after concurrent chemoradiotherapy (CCRT).MethodsWe retrospectively analyzed 163 newly diagnosed ESCC patients treated with CCRT. Eighty patients (training set) were randomly selected to generate cut-off SUVmean and NLR values by receiver operating characteristic (ROC) curve analysis and to establish a predictive model by using the independent predictors of treatment outcomes. Then, we evaluated the performance of the prediction model regarding treatment outcomes in the testing set (n = 83) and in all sets.ResultsA high SUVmean (> 5.81) and high NLR (> 2.42) at diagnosis were associated with unfavorable treatment outcomes in patients with ESCC. The prediction model had a better performance than the simple parameters (p < 0.05). With a cut-off value of 0.77, the prediction model significantly improved the specificity and positive predictive value for treatment response (88.9 and 92.1% in the training set, 95.8 and 97.1% in the testing set, and 92.2 and 91.8% in all sets, respectively).ConclusionsThe pretreatment SUVmean and NLR were independent predictors of treatment response in ESCC patients treated with CCRT. The predictive model was constructed based on these two parameters and provides a highly accurate tool for predicting patient outcomes.

TREATMENT OUTCOME AND DETERMINANTS AMONG PATIENTS WITH VISCERAL LEISHMANIASIS IN ARBA MINCH GENERAL HOSPITAL LEISHMANIASIS RESEARCH AND TREATMENT CENTER, GAMO GOFA ZONE, SNNPR, ETHIOPIA

- Introduction: Visceral Leishmania represents a challenging diagnosis and treatment because the clinical picture of Visceral Leishmaniasis, so that the treatment outcome is compromised with many factors, thus study try to asses real picture of treatment outcome with determinants. Objective: To assess treatment outcome and determinant factors among patient with visceral Leishmaniasis in Arba Minch General Hospital Leishmania Research and Treatment Center. Methods: Institution-based, Cross-sectional, retrospective study was conducted among Leishmaniasis patients in Arba Minch general hospital. Patient charts that have been treated from January 2011-December 2015 were reviewed. A total of 348 charts were selected by Simple Random Sampling technique and included in the study. The data were entered and cleaned using Epi-info version 7.0 and analysis was carried out using SPSS-20 statistical packages. Multi-variate logistic regression analysis was carried out to identify the independent predictors of treatment outcome. Result: A total of 348 patient's charts were included in the study. The prevalence of poor outcome was found to be 8.6%. The presence of bleeding/Epsitaxis[AOR=5;95% CI:1.3,19.3], tuberculosis[AOR=3.7;95%CI:1.83,6.3], septic syndrome[AOR=4.3;95% CI: 6.1,32], and adverse drug side effect[AOR=4.5;95%CI:2.73,13.6] were the independent predictors of treatment outcome. Conclusion and recommendation: The prevalence of poor treatment outcome among patients with VL in the study area is high. Concomitant infection; bleeding/Epsitaxis, tuberculosis, septic syndrome and adverse side effect were independently associated with poor treatment outcome. The clinical management of VL in co-infected patients is a major challenge that requires new treatment approaches to improve its outcome.

Predicting success of methotrexate treatment by pretreatment HCG level and 24-hour HCG increment.

To evaluate β-human chorionic gonadotropin (β-HCG) level and its 24-hour increment as predictors of successful methotrexate treatment for ectopic pregnancy. Data were retrospectively reviewed from women with ectopic pregnancy who were treated by single-dose methotrexate (50mg/m2 ) at a university hospital in Jerusalem, Israel, between January 1, 2000, and June 30, 2015. Serum β-HCG before treatment and its percentage increment in the 24hours before treatment were compared between treatment success and failure groups. Sixty-nine women were included in the study. Single-dose methotrexate treatment was successful for 44 (63.8%) women. Both mean β-HCG level and its 24-hour increment were lower for women with successful treatment than for those with failed treatment (respectively, 1224IU\L vs 2362IU\L, P=0.018; and 13.5% vs 29.6%, P=0.009). Receiver operator characteristic curve analysis yielded cutoff values of 1600IU\L and 14% increment with a positive predictive value of 75% and 82%, respectively, for treatment success. β-HCG level and its 24-hour increment were independent predictors of treatment outcome by logistic regression (both P<0.01). A β-HCG increment of less than 14% in the 24hours before single-dose methotrexate and serum β-HCG of less than 1600IU\L were found to be good predictors of treatment success.

Stages of Change Model has Limited Value in Explaining the Change in Use of Cannabis among Adolescent Participants in an Efficacious Motivational Interviewing Intervention

ABSTRACTPreviously, a Dutch randomized controlled trial evaluating an intervention aimed at changing adolescents’ cannabis use, called Moti-4, has shown its efficacy. A secondary analysis of the Moti-4 data investigated the process of change specified by the Stage of Change (SOC) model in cannabis use during the trial. Seventy-one Moti-4 participants and 60 controls were recruited for the study with a pre-test, post-test (T1), and six-month follow-up (T2). All participants showed signs of problematic cannabis use. No contribution of the Moti-4 intervention to a change in SOC between T1 and T2 was found. Although motivation for treatment and motivation for change can be conceived as independent predictors of treatment outcome, the SOC a person is in does not mediate the effect of the intervention on change in cannabis use. However, a reduction in cannabis use was associated with a positive change in “action willingness,” in line with the SOC model. In contrast to model expectations, a higher score on “contemplation” is associated with a higher cannabis consumption. Results highlight both the limitations and usefulness of the SOC model. Future interventions may focus more on the stage of “action willingness,” as well as on perceived social norms.

Exacerbation of headache during dihydroergotamine for chronic migraine does not alter outcome.

To evaluate whether headache exacerbation associated with IV dihydroergotamine (DHE) infusion predicts medium-term headache outcome in patients with chronic migraine. This was a retrospective chart review study of the UCSF Headache Center's use of IV DHE for chronic migraine from 2008 to 2012. Medium-term headache outcome was assessed at 6-week follow-up. Univariate and multivariate logistic regression models were used to assess for predictors of outcome. Patients with chronic migraine (n = 274) were treated with a course of IV DHE. Of 214 with 6-week follow-up, 78% had medium-term headache benefit. In a univariate logistic regression model, headache exacerbation with DHE was associated with lower odds of a positive medium-term headache outcome (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.20-0.91). However, in the multivariate logistic regression model, headache exacerbation was no longer an independent predictor of treatment outcome (OR 0.65, 95% CI 0.28-1.51). Factors that independently predicted outcome were nausea (OR 0.12, 95% CI 0.02-1.00, p = 0.05), age (OR 1.68 for each decade increase in age, 95% CI 1.24-2.28), and medication overuse (OR 0.42, 95% CI 0.18-0.97). After controlling for nausea and other factors, headache exacerbation with DHE infusions is not an independent predictor of poor headache outcome and clinicians should not interpret its presence as a reason to stop treatment. The focus of management should be on controlling nausea as it is the most important modifiable factor in achieving a good headache outcome with an inpatient course of IV DHE for chronic migraine.