scholarly journals Elevated Post-transplant Levels of Neopterin are Associated with Poorer long-term Graft Outcome

Pteridines ◽  
2004 ◽  
Vol 15 (3) ◽  
pp. 113-119 ◽  
Author(s):  
S. O. Grebe ◽  
U. Kuhlmann ◽  
T. F. Müller

Abstract Chronic allograft nephropathy (CAN) and death with functioning graft due to cardiovascular disease (CVD) are the key determinants for long-term renal allograft survival. Chronic allograft nephropathy and cardiovascular disease are seen as manifestations of a single disease entity with a common pathogenesis including inflammation and accelerated atherogenesis. Therefore we investigated the relation between early post-transplant inflammatory burden and long-term graft survival. In 64 consecutive renal transplant patients the acute phase reactants serum amyloid A (SAA) and serum C-reactive protein (S-CRP) as well as the macrophage product neopterin in urine (U-NEOP) and serum (S-NEOP) were determined daily during the immediate postoperative period (mean p.o.obs. χ = 29.2 ± 8.7 days, total of Σ = 1869 days). SAA and CRP were measured with high-sensitive assays (in mg/1; immune nephelometry, Dade Behring Co., Marburg, Germany), NEOP was measured with ELISA-technique (Brahms, Berlin, Germany) and related to serum and urine creatinine levels, resp. (in μπιοΐ/mol creatinine). The association between the mean values of these parameters and the survival distribution function of the 64 patients was tested using the log rank test and the Wilcoxon-test. In this analysis graft loss was defined as either resumption of dialysis treatment or patient death with functioning graft. The 1- and 5- year graft survival rates in our patients were 93% and 76%, resp. The markers showed the following mean post-transplant levels: S-CRP χ = 21.3 ± 16.1 mg/1, SAA χ = 10.1 ± 6.5 mg/1, U-NEOP χ = 602 ± 427 mmol/mol creatinine and S-NEOP χ = 81 ± 60 μπιοΐ/mol creatinine. Both log rank test and Wilcoxon-test provided evidence that the graft survival is negatively related to the post-transplant levels of U-NEOP (p = 0.009 and ρ = 0.027, resp.). The markers S-NEOP (p = 0.074 and ρ = 0.116, resp.), SAA (p = 0.599 and ρ = 0.294, resp.), and S-CRP (p = 0.059 and ρ = 0.358, resp.) did not reach statistical significance. These findings support the impact of the inflammatory burden on graft survival. In particular, elevated post-transplant neopterin values, reflecting activated innate and adaptive responses, are predictive for long-term graft outcome.

2015 ◽  
Vol 15 (4) ◽  
pp. 399-405 ◽  
Author(s):  
Paul J. Marano ◽  
Scellig S. D. Stone ◽  
John Mugamba ◽  
Peter Ssenyonga ◽  
Ezra B. Warf ◽  
...  

OBJECT The role of reopening an obstructed endoscopic third ventriculostomy (ETV) as treatment for ETV failure is not well defined. The authors studied 215 children with ETV closure who underwent successful repeat ETV to determine the indications, long-term success, and factors affecting outcome. METHODS The authors retrospectively reviewed the CURE Children's Hospital of Uganda database from August 2001 through December 2012, identifying 215 children with failed ETV (with or without prior choroid plexus cauterization [CPC]) who underwent reopening of an obstructed ETV stoma. Treatment survival according to sex, age at first and second operation, time to failure of first operation, etiology of hydrocephalus, prior CPC, and mode of ETV obstruction (simple stoma closure, second membrane, or cisternal obstruction from arachnoid scarring) were assessed using the Kaplan-Meier survival method. Survival differences among groups were assessed using log-rank and Wilcoxon methods and a Cox proportional hazards model. RESULTS There were 125 boys and 90 girls with mean and median ages of 229 and 92 days, respectively, at the initial ETV. Mean and median ages at repeat ETV were 347 and 180 days, respectively. Postinfectious hydrocephalus (PIH) was the etiology in 126 patients, and nonpostinfectious hydrocephalus (NPIH) in 89. Overall estimated 7-year success for repeat ETV was 51%. Sex (p = 0.46, log-rank test; p = 0.54, Wilcoxon test), age (< vs > 6 months) at initial or repeat ETV (p = 0.08 initial, p = 0.13 repeat; log-rank test), and type of ETV obstruction (p = 0.61, log-rank test) did not affect outcome for repeat ETV (p values ≥ 0.05, Cox regression). Those with a longer time to failure of initial ETV (> 6 months 91%, 3–6 months 60%, < 3 months 42%, p < 0.01; log-rank test), postinfectious etiology (PIH 58% vs NPIH 42%, p = 0.02; log-rank and Wilcoxon tests) and prior CPC (p = 0.03, log-rank and Wilcoxon tests) had significantly better outcome. CONCLUSIONS Repeat ETV was successful in half of the patients overall, and was more successful in association with later failures, prior CPC, and PIH. Obstruction of the original ETV by secondary arachnoid scarring was not a negative prognostic factor, and should not discourage the surgeon from proceeding. Repeat ETV may be a more durable solution to failed ETV/CPC than shunt placement in this context, especially for failures at more than 3 months after the initial ETV. Some ETV closures may result from an inflammatory response that is less robust at the second operation.


2021 ◽  
Author(s):  
Tingdan Zheng ◽  
Wuqi Song ◽  
Aiying Yang

Abstract Objective Here we performed the Bioinformatics analysis on the data from The Cancer Genome Atlas (TCGA), in order to find the correlation between the expression of ATP Binding Cassette (ABC) Transporters’ genes and hepatocellular carcinoma (HCC) prognosis; Methods Transcriptome profiles and clinical data of HCC were obtained from TCGA database. Package edgeR was used to analyze differential gene expression. Patients were divided into low-ABC expression and high-ABC expression groups based on the median expression level of ABC genes in cancer. The overall survival and short-term survival (n= 341) of the two groups was analyzed using the log-rank test and Wilcoxon test; Results We found that ABC gene expression was correlated with the expression of PIK3C2B (p<0.001, ABCC1: r=0.27; ABCC10: r=0.57; ABCC4: r=0.20; ABCC5: r=0.28; ABCB9: r=0.17; ABCD1: r=0.21). All patients with low-ABC expression showed significantly increased overall survival. Significantly decreased overall survival (Log-rank test: p<0.05, Wilcoxon test: p<0.05) was found in patients with high expression of ABCC1 (HR=1.58), ABCD1 (HR=1.45), ABCC4 (HR=1.56), and ABCC5 (HR=1.64), while decreased short-term survival (Log-rank test: p>0.05, Wilcoxon test: p<0.05) was correlated with the increased expression of ABCC10 (HR=1.29), PIK3C2B (HR=1.29) and ABCB9 (HR=1.23); Conclusions Our findings indicate that the specific ABC gene expression correlates with the prognosis of HCC. Therefore, ABC expression profile could be a potential indicator for HCC patients.


2020 ◽  
Vol 25 (1) ◽  
pp. 33-38
Author(s):  
A. M. Soldatova ◽  
V. A. Kuznetsov ◽  
T. P. Gizatulina ◽  
L. M. Malishevsky ◽  
S. M. Dyachkov

Aim. To assess the relationship between the prolonged PR interval (≥200 ms) and the long-term survival of patients undergoing cardiac resynchronization therapy (CRT).Material and methods. A total of 85 patients (mean age — 55,1Ѓ}9,9 years; men — 81,2%) with NYHA class II-IV heart failure (HF) were examined. The mean follow-up was 34,0Ѓ}21,2 months. Patients with PR<200 ms (n=52) made up group I, with PR≥200 ms (n=33) — group II. Then the patients were divided into subgroups depending on the QRS duration: ≥150 ms (n=33 in group I and n=14 in group II, respectively) <150 ms (n=19 in group I and n=19 in group II, respectively).Results. In patients of group II, a history of myocardial infarction (MI) was more often registered (p=0,005), left ventricular ejection fraction (LVEF) was lower (p=0,032). In a multivariate analysis, MI (OR 3,217; CI 95% 1,188-8,712; p=0,022) and LVEF value (OR 0,869; CI 95% 0,780-0,968; p=0,011) had a significant relationship with the PR interval prolongation (≥200 ms). The survival of patients of group I was 59,6%, group II — 18,2% (Log-rank test p<0,001). According to Cox regression model, the initial left ventricle end-systolic volume (OR 1,012; 95% CI 1,006-1,017; p<0,001), inferior wall MI (OR 1,690; 95% CI 1,131-2,527; p=0,011) and PR interval ≥200 ms (OR 2,179; 95% CI 1,213–3,915; p=0,009) were associated with long-term mortality. In patients with PR≥200 ms, survival rate was low, regardless of the QRS duration (21,4% in patients with QRS≥150 ms, 15,8% in patients with QRS<150 ms; Log-rank test p=0,698) In patients with PR<200 ms, the survival rate of patients with QRS≥150 ms was 72,7%, and for patients with QRS<150 ms — 36,8% (Log-rank test p=0,031).Conclusion. In HF patients, PR interval prolongation (≥200 ms) is associated with long-term mortality increase. The highest survival rates were observed in patients with PR<200 ms and QRS≥150 ms. In patients with QRS≥150 ms, the presence of PR≥200 ms should be considered as an additional criterion for CRT.


1993 ◽  
Vol 11 (5) ◽  
pp. 1007-1007 ◽  
Author(s):  
Rodger M. Pryzant ◽  
Marvin L. Meistrich ◽  
Gene Wilson ◽  
Barry Brown ◽  
Peter McLaughlin

The last sentence of the Results section of the February 1993 report "Long-Term Reduction in Sperm Count After Chemotherapy With and Without Radiation Therapy for Non-Hodgkin's Lymphomas" by Pryzant et al (J Clin Oncol 11:239–247, 1993) should have read: "The recovery of those patients who received less than 9.5 g/m2 of cyclophosphamide was significantly greater than those who received more than 9.5 g/m2 of cyclophosphamide (P = .00092, log-rank test)." The unit of measure for cyclophosphamide in the legend for Fig 4 and in the next to last paragraph of the Discussion should have been g/m2.


Medicina ◽  
2013 ◽  
Vol 49 (5) ◽  
pp. 36 ◽  
Author(s):  
Daimantas Milonas ◽  
Giedrius Skulčius ◽  
Ruslanas Baltrimavičius ◽  
Stasys Auškalnis ◽  
Marius Kinčius ◽  
...  

Objective. The aim of our study was to compare long-term oncological outcomes following nephron-sparing surgery (NSS) and radical nephrectomy (RN) for renal cell carcinoma (RCC) 4 to 7 cm in diameter. Material and Methods. The study included patients who underwent RN or NSS for RCC 4 to 7 cm in diameter between 1998 and 2009. The studied groups were compared with respect to the patients’ age, sex, physical status according to the American Society of Anesthesiologists Physical classification, histological type, stage, tumor size, grade, duration of the operation, and complications. Survival was established using the Kaplan-Meier method. The risk factors for survival were analyzed using a multivariate Cox regression model. Results. During the study, 351 patients underwent surgery: 317 patients (90.3%) underwent RN, and 34 (9.7%), NSS. The compared groups differed with respect to tumor size (P=0.001) and stage (P=0.006). The overall estimated 12-year survival was 53.7% after RN and 55.2% after NSS (log-rank test P=0.437). The 12-year cancer-specific survival in the RN and NSS groups was 69.6% and 80.6%, respectively (log-rank test P=0.198). Pathological stage and patients’ age were the major factors affecting both overall and cancer-specific survival. The type of surgery (NSS or RN) had no effect on survival. Conclusions. Our study showed that nephron-sparing surgery is a safe technique compared with radical nephrectomy that ensures good oncological control in the treatment of renal cell carcinoma measuring 4 to 7 cm and may be proposed as the treatment of choice for renal tumors not only up to 4 cm, but also 4 to 7 cm in size.


2019 ◽  
Vol 111 (11) ◽  
pp. 1186-1191 ◽  
Author(s):  
Julien Péron ◽  
Alexandre Lambert ◽  
Stephane Munier ◽  
Brice Ozenne ◽  
Joris Giai ◽  
...  

Abstract Background The treatment effect in survival analysis is commonly quantified as the hazard ratio, and tested statistically using the standard log-rank test. Modern anticancer immunotherapies are successful in a proportion of patients who remain alive even after a long-term follow-up. This new phenomenon induces a nonproportionality of the underlying hazards of death. Methods The properties of the net survival benefit were illustrated using the dataset from a trial evaluating ipilimumab in metastatic melanoma. The net survival benefit was then investigated through simulated datasets under typical scenarios of proportional hazards, delayed treatment effect, and cure rate. The net survival benefit test was computed according to the value of the minimal survival difference considered clinically relevant. As comparators, the standard and the weighted log-rank tests were also performed. Results In the illustrative dataset, the net survival benefit favored ipilimumab [Δ(0) = 15.8%, 95% confidence interval = 4.6% to 27.3%, P = .006]. This favorable effect was maintained when the analysis was focused on long-term survival differences (eg, >12 months, Δ(12) = 12.5% (95% confidence interval = 4.4% to 20.6%, P = .002). Under the scenarios of a delayed treatment effect and cure rate, the power of the net survival benefit test compared favorably to the standard log-rank test power and was comparable to the power of the weighted log-rank test for large values of the threshold of clinical relevance. Conclusion The net long-term survival benefit is a measure of treatment effect that is meaningful whether or not hazards are proportional. The associated statistical test is more powerful than the standard log-rank test when a delayed treatment effect is anticipated.


2019 ◽  
Vol 6 (1) ◽  
pp. e000465
Author(s):  
C.Tji-Joong Gan ◽  
Chris Ward ◽  
Gerard Meachery ◽  
James Laurence Lordan ◽  
Andrew J Fisher ◽  
...  

IntroductionAzithromycin stabilises and improves lung function forced expiratory volume in one second (FEV1) in lung transplantation patients with bronchiolitis obliterans syndrome (BOS). A post hoc analysis was performed to assess the long-term effect of azithromycin on FEV1, BOS progression and survival .MethodsEligible patients recruited for the initial randomised placebo-controlled trial received open-label azithromycin after 3 months and were followed up until 6 years after inclusion (n=45) to assess FEV1, BOS free progression and overall survival.ResultsFEV1 in the placebo group improved after open-label azithromycin and was comparable with the treatment group by 6 months. FEV1 decreased after 1 and 5 years and was not different between groups. Patients (n=18) with rapid progression of BOS underwent total lymphoid irradiation (TLI). Progression-free survival (log-rank test p=0.40) and overall survival (log-rank test p=0.28) were comparable. Survival of patients with early BOS was similar to late-onset BOS (log-rank test p=0.74).DiscussionLong-term treatment with azithromycin slows down the progression of BOS, although the effect of TLI may affect the observed attenuation of FEV1 decline. BOS progression and long-term survival were not affected by randomisation to the placebo group, given the early cross-over to azithromycin and possibly due to TLI in case of further progression. Performing randomised placebo-controlled trials in lung transplantation patients with BOS with a blinded trial duration is feasible, effective and safe.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22157-e22157
Author(s):  
M. Batus ◽  
R. Myint ◽  
J. Coon ◽  
S. Basu ◽  
K. Kaiser ◽  
...  

e22157 Background: Minimal advances have been made in the treatment of SCLC. Molecular markers may allow us to better stratify patients (pts) for new treatment options and drug combinations. The objective of our study was to determine the frequency and potential prognostic significance of N-cadherin (N-cad), E-cadherin (E-cad), ERCC1, and c-kit (CD117) expression in SCLC. Methods: Tissue from 132 pts with SCLC was retrospectively stained for N-cad, E-cad, ERCC1, and c-kit. Frequency of expression (% of tumor cells staining positive) was measured on a scale of 0–4 (freq 0=no expression (<1%), freq 1=1–10%, freq 2=11–35%, freq 3=36–70%, freq 4=71–100%). Charts were reviewed for stage, performance status, date of diagnosis/death, survival, and treatment (type, dates, response). The frequency of molecular markers was correlated with clinical data and overall survival. Results: Age range 42 to 97 years, 65 male:67 female, and 64 had limited and 68 had extensive stage. Of the 132 pts, 75% had tumors that expressed (frequency ≥ 1) N-cad, 58% E-cad, 70% ERCC1, and 55% c-kit. Comparing tumor marker expression with survival using either the Log-Rank Test or the Wilcoxon Test, there was no significant association for N-cad, E-cad, or ERCC1. However, tumors that expressed c-kit with frequency ≥ 3 had a trend toward superior survival compared with frequency < 3. Median survival for c-kit frequency ≥ 3 was 496 days compared to 312 days for frequency < 3 (p = 0.09, Log-Rank Test). Conclusions: In our retrospective study of 132 SCLC pts, we found that all 4 markers were expressed in greater than 50% of specimens, and that higher c-kit expression was associated with marginally significant increase in overall survival. Though previous experience with imatinib alone or with chemotherapy showed limited clinical activity in unselected SCLC pts, given preclinical synergy with cisplatin, it seems reasonable to consider combination therapy with cisplatin/etoposide and imatinib in pts selected for high c-kit expression. [Table: see text] No significant financial relationships to disclose.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11061-11061
Author(s):  
Brett A. Schroeder ◽  
Chad He ◽  
Yuzheng Zhang ◽  
Michael Wagner ◽  
Robin Lewis Jones ◽  
...  

11061 Background: TRB is FDA approved drug for the treatment of liposarcoma (Lipo) and leiomyosarcoma (LMS). The aim of this study was to evaluate potential biomarkers associated with prolonged benefit in patients treated with TRB at our center prior to 2016. Methods: We performed a retrospective search of UW/FHCRC CASIS database to identify patients treated with TRB prior to 2016. Demographic variables and clinical variables (such as histology and treatment) were retrieved. Statistics were performed with R 3.4.1 software. Pairwise Pearson’s correlation was calculated for the # of prior chemotherapy regimens with # of TRB cycles. The Kaplan-Meir method was used to evaluate overall survival (OS). Log-rank test was conducted to compare groups in terms of OS. Results: 145 sarcoma patients treated with TRB were identified with a mean follow up of 5 years (generally on NCT01427582 or NCT01343277). Patients averaged 1.9 prior chemotherapy regimens prior to TRB (range 0-7 regimens) and received an average of 5.6 TRB doses (range 1-25 doses). Subtypes are listed on table. The # of prior regimens was negatively correlated with the # of TRB cycles that patients received (pairwise correlation coefficient = -1.77; p=0.034), suggesting that multiple prior treatment lines either made TRB less tolerable or made sarcoma less sensitive to TRB. The median OS for this heavily treated metastatic population was 0.5 years. However, patients who were able to stay on TRB for more than 5 cycles had a significantly higher OS (p=0.001). While only 23% of patients who received less than 5 cycles of TRB were alive at 5 years (95% CI: 0.15, 0.32), 53% of those who received 5 or more cycles of (95% CI: 0.39, 0.65) were alive at 5 years. Conclusions: TRB may be more effective when administered as an earlier line of therapy. Patients who are able to stay on TRB for a longer duration had a significant improvement in OS. Detailed subset analysis will be presented as will initial findings of our biomarker work. These retrospective data warrant further evaluation. Clinical trial information: NCT01427582 or NCT01343277. [Table: see text]


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S072-S073
Author(s):  
S Festa ◽  
M L Scribano ◽  
A Aratari ◽  
C Bezzio ◽  
M Principi ◽  
...  

Abstract Background The appropriate maintenance treatment for patients with acute severe ulcerative colitis (ASUC) responsive to intravenous steroids (IVS) is still a matter of debate. Although major Guidelines consider thiopurine maintenance an option in this setting, the long-term benefit of early immunomodulator (IMMs) initiation is not well established. The aim of our study was to explore the long-term outcome of patients with ASUC responsive to IVS who received different maintenance strategies Methods In a multicenter retrospective study, all patients with ASUC hospitalized between January 2005 and December 2017 in 14 Italian IBD referral centres were reviewed. Thiopurine and biologic-naïve patients experiencing their first acute severe attack and who responded to IVS were included in the study. Maintenance treatment was prescribed by attending physicians according to their clinical judgment. The main outcomes were recurrent flares requiring escalation of therapy, new hospitalization, and long-term colectomy rate. The Kaplan-Meier survival method was used to estimate the cumulative probability of a course without the main outcomes. Differences between curves were tested using the log-rank test. A propensity score matching analysis was performed to establish comparable groups of patients who received different maintenance treatment Results Overall 372 patients were reviewed. Of these, 141 met the inclusion criteria (males 61.7%, median age 34.5 (IQR 23–50). After response to IVS, 82 patients (58.1%) received maintenance treatment with aminosalicylates, 42 (29.8%) received IMMs and 17 (12.1%) were maintained with scheduled infliximab (IFX) + thiopurines. After a median follow-up of 48 (IQR 25–90) months, 94 patients (68.8%) experienced a flare requiring escalation of therapy, 51 (36.1%) required new hospitalization and 18 (12.8%) underwent colectomy. After 12, 36 and 60 months after the acute attack, the cumulative probability of a course without escalation of therapy was 59.6%, 33.3% and 23.1%; the cumulative probability of a hospitalization-free course was 83.9%, 67.4% and 59.5%; the cumulative probability of a colectomy-free course was 96.3%, 90.2%, and 88.9%. No differences were observed between patients receiving aminosalicylates, IMMs or IFX as maintenance treatment (log-rank test: p= 0.39; p = 0.41; p = 0.11 respectively). After a propensity score matching analysis, no significant difference in main outcomes was observed between patients maintained with aminosalicylates or IMMs/IFX Conclusion IMM-naïve ASUC patients responsive IVS remain at risk of relapse requiring escalation of therapy. Early IMMs introduction after the acute attack did not reduce the risk of escalation of therapy, hospitalization or colectomy


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