Incidence, Management, and Outcome of Symptomatic Postoperative Posterior Fossa Pseudomeningocele: A Retrospective Single-Institution Experience

2016 ◽  
Vol 12 (3) ◽  
pp. 298-304 ◽  
Author(s):  
Gabriel A Smith ◽  
Madeline P Strohl ◽  
Sunil Manjila ◽  
Jonathan P Miller
Keyword(s):  
Posterior Fossa ◽  
Proportional Hazards ◽  
Management Strategies ◽  
Treatment Strategies ◽  
Multivariate Logistic Regression Analysis ◽  
Cox Proportional Hazards ◽  
Posterior Fossa Surgery ◽  
Single Institution ◽  
Clinical Resolution ◽  
Lumbar Drainage

Abstract BACKGROUND Pseudomeningocele is a source of considerable morbidity after posterior fossa surgery, but incidence and optimal management strategies are unclear. OBJECTIVE To define risk factors, evaluate management strategies, and identify predictors of resolution. METHODS A prospectively maintained database of 687 consecutive posterior fossa operations at a single institution was analyzed to identify cases of symptomatic postoperative pseudomeningocele. Retrospective analysis of treatment strategies and outcome was performed. RESULTS Overall rate of symptomatic postoperative pseudomeningocele was 14.1% (97 cases). The highest rate was for midline posterior fossa surgery (16.5%), and the lowest rate was for retrosigmoid surgery (11.9%). Multivariate logistic regression analysis revealed that the presence of increased ventricle size on postoperative imaging predicted significantly higher risk of failure of lumbar drainage (odds ratio, 6.57; 95% confidence interval [CI], 1.18-36.59; P < .05). Cox proportional hazards analysis revealed that time to clinical resolution was significantly associated only with use of temporary lumbar drainage (hazards ratio, 2.28; 95% CI, 1.04-5.00; P < .05), and time to radiographic resolution was associated only with placement of a ventricular shunt (hazards ratio, 2.84; 95% CI, 1.19-6.78; P < .05). CONCLUSION Pseudomeningocele is a common complication after posterior fossa surgery, but incidence is not related to age or medical comorbidity. Postoperative ventriculomegaly portends failure of temporary cerebrospinal fluid diversion, and early consideration of shunting might be appropriate in such cases. In the absence of ventriculomegaly, temporary use of a lumbar drain leads to earlier clinical resolution, but complete radiographic resolution is rare when a permanent shunt is not implanted. Further research should be performed to establish the most effective treatment strategy.

Analysis of the effect of adjuvant therapy on overall survival for resected gallbladder adenocarcinoma using the National Cancer Database.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 360-360
Author(s):  
David G. Brauer ◽  
Kian-Huat Lim ◽  
Maria Majella Doyle ◽  
William G. Hawkins ◽  
William C. Chapman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Proportional Hazards ◽  
Treatment Strategies ◽  
Cox Proportional Hazards ◽  
National Cancer Database ◽  
Clinical Scenarios ◽  
Gallbladder Adenocarcinoma ◽  
One Year

360 Background: The effect of adjuvant chemotherapy on survival after resection for gallbladder adenocarcinoma (GBC) is based on limited evidence. Since prospective trials are not generally practical for GBC, we sought to evaluate current best evidence to evaluate the role of adjuvant chemotherapy in multiple clinical scenarios by analyzing data from the U.S. National Cancer Database (NCDB). Methods: Patients who underwent resection for GBC diagnosed between 2004 and 2012 were identified in the NCDB. The effect of adjuvant therapy on overall survival (OS) was assessed using Kaplan-Meier analysis and Cox proportional hazards regression modeling. Results: 10,402 patients met inclusion criteria. Median follow-up was 14 months. Median survival was 16 months. One- and five-year OS were 57% and 23%, respectively. 3,509 patients (34%) received any modality of adjuvant therapy. Receipt of adjuvant therapy improved one-year OS (63% vs 55%, p < 0.01), but median OS was minimally changed (17 vs 15 months, NS). Adjuvant therapy was associated with improved one-year OS in T3 and T4N1 disease (Table 1). Only chemoradiation therapy was associated with improved one-year OS for T2 disease. Adjuvant chemotherapy was associated with worse one-year OS in T1N0 disease. Conclusions: Using data from the US NCDB, adjuvant therapy for resected gallbladder adenocarcinoma is associated with improved one-year overall survival with the exception of T1N0 disease. In the absence of prospective studies in this rare disease, retrospective data can provide insights into successful treatment strategies and guidelines for GBC. [Table: see text]

scholarly journals The Prognostic Impact of Tumor Differentiation on Recurrence and Survival after Resection of Hepatocellular Carcinoma Is Dependent on Tumor Size

Liver Cancer ◽  
2021 ◽  
pp. 1-12
Author(s):  
Hiroji Shinkawa ◽  
Shogo Tanaka ◽  
Daijiro Kabata ◽  
Shigekazu Takemura ◽  
Ryosuke Amano ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatic Resection ◽  
Tumor Size ◽  
Proportional Hazards ◽  
Treatment Strategies ◽  
Early Recurrence ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
Tumor Differentiation ◽  
Negative Effects

<b><i>Introduction:</i></b> The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). <b><i>Methods:</i></b> A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. <b><i>Results:</i></b> In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07–1.59), 1.07 (95% CI 0.89–1.28), 1.31 (95% CI 1.06–1.62), and 1.81 (95% CI 1.03–3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (<i>p</i> = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring &#x3c;2, ≥2 and &#x3c;5, and ≥5 cm were 1.22 (95% CI 0.69–2.14), 1.33 (95% CI 1.02–1.73), and 1.58 (95% CI 1.04–2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46–1.57), 1.34 (95% CI 1.01–1.8), and 1.57 (95% CI 1.03–2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83–4.3) in patients with tumors measuring ≥2 and &#x3c;5 cm and 2.33 (95% CI 0.98–5.54) in those with tumors measuring ≥5 cm. <b><i>Conclusions:</i></b> Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC.

Leptomeningeal disease and breast cancer: Relationship of outcome and subtype.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 601-601
Author(s):  
Sausan Abouharb ◽  
Joe Ensor ◽  
Monica Elena Loghin ◽  
Ruth Katz ◽  
Ana M. Gonzalez-Angulo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Proportional Hazards ◽  
Treatment Strategies ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Intrathecal Therapy ◽  
Leptomeningeal Disease ◽  
Tumor Subtype ◽  
Dismal Prognosis ◽  
Significant Difference

601 Background: Breast cancer (BC) is one of the most common tumors to involve the leptomeninges. Outcome of leptomeningeal disease (LMD) across BC subtypes is not well documented. We aimed to characterize clinical features and outcomes of LMD based on BC subtypes. Methods: We retrospectively reviewed medical records of patients diagnosed with LMD from BC (1997 to 2012). All patients had BC. Cases of LMD were based on the presence of neoplastic cells on cerebrospinal fluid examination and/or evidence of LMD by imaging studies. Survival was estimated by the Kaplan-Meier method and significant differences in survival were determined by Cox proportional hazards or log-rank tests. Results: 232 patients were included, 189 of them had available tumor subtype classified as: hormone receptor positive (HR+) BC N=67 (35.5%), human epidermal growth factor receptor 2 positive (HER2+) N=55 (29%), and 67 (35.5%) triple-negative BC (TNBC). Median age at diagnosis of LMD was 49.7 years. (Range 24-89). Median overall survival (OS) from LMD diagnosis across all subtypes was 3.1 months (95% CI, 2.5 to 3.7). Median OS correlated with BC subtype: 3.7 months (95% CI: 2.4, 6.0) in HR+, 4.0 months (95% CI: 2.6, 6.9) in HER2+, and 2.2 months (95% CI: 1.5, 3.0) in TNBC, (p=0.0002). There was an 11.4% chance a patient diagnosed with LMD would survive 1 year and the chance of surviving at least 3 years was 1.3%. When age was used as a continuous variable, older age was associated with worse outcome (p<0.0001). Patients with HER2+ BC and LMD were more likely to have received systemic therapy (ST) (70%), compared to HR+ (41%) and TNBC (41%) (p=0.002). 38% of patients with HER2+ BC received HER2 directed therapy. There was no difference in the use of intrathecal therapy (IT) (52%) across subtypes (p=0.3). Use of IT therapy (p<0.0001) and ST (p<0.0001) were both associated with improved age-adjusted OS. After adjusting for age, ST, there was no difference in OS between patients with HR+ and HER2+ BC (p =0.14), but a significant difference remained between TNBC and HER2+ BC (p < 0.0001). Conclusions: LMD carries a dismal prognosis. Our data shows that OS correlates with tumor subtype. Patients with TNBC had a significantly shorter OS compared to patients with HER2+ BC. New treatment strategies are needed.

A multistate model for follicular lymphoma (FL) patients (pts) who experience early progression.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18164-e18164
Author(s):  
Hiromi Terawaki ◽  
Caglar Caglayan ◽  
Qiushi Chen ◽  
Ashish Rai ◽  
Turgay Ayer ◽  
...  
Keyword(s):  
Markov Model ◽  
Median Time ◽  
Median Survival ◽  
Proportional Hazards ◽  
Treatment Strategies ◽  
Initial Therapy ◽  
Observation Time ◽  
Cox Proportional Hazards ◽  
Health States ◽  
The Impact

e18164 Background: FL is the second most frequent lymphoma subtype. Approximately 20% of FL pts experience disease progression within two years of initial chemo-immunotherapy. Currently, there is no standard of care approach for treatment of these pts. Methods: Using Surveillance, Epidemiology, and End Results (SEER) registry data from 2000 through 2009 linked to Medicare claims data through 2011, we identified pts who received second line therapy within 2 years of their initial therapy and incorporated their clinical, demographic, treatment, and outcomes data into a multi-state Markov model to study the impact of first, second and third line therapies. Treatments were categorized as rituximab (R), R-cyclophosphamide and vincristine (RCVP), R- cyclophosphamide, hydroxydaunorubicin, and vincristine (RCHOP), and other R-containing regimens. The Aalen-Johansen estimator was used to estimate the likelihood of being in 1 of 4 health states: dead or alive following treatment (TX) 1, 2 or 3. A Cox proportional hazards regression model was fitted for each possible transition between the model states to identify significant factors affecting time of progression to the next line treatment or death. Results: Data for 5234 pts were incorporated into the model. The median observation time before TX1 was 1.4 months (range 0-125 months). Overall, the median time from TX1 to TX2 was 3.1 (95% CI 2.9-3.2) months and median survival was 33.3 (32.2-34.3) months. For pts who received R, RCVP, and RCHOP as TX1, the median time to TX2 (range) was 5.4 (4.9-5.8), 4.2 (3.6-4.7), and 3.3 (2.9-3.5) months, respectively. These treatments were associated with a median survival of 33 (31-35), 31 (28-32), and 36 (34-39) months, respectively. For pts who received R, RCVP, and RCHOP as TX2 the median time to TX3 was 5.0 (4.3- 5.3), 3.2 (2.7-3.9), and 2.7 (2.3-3.1) months, respectively. Conclusions: This multi-state Markov model using SEER-Medicare data, provides means to examine sequential treatment strategies that influence outcomes for pts with poor-risk FL and factors that influence transition points within each strategy. This modeling approach can help identify where interventions can have the greatest impact for these pts with unmet clinical needs.

scholarly journals MicroRNA-mRNA networks define translatable molecular outcome phenotypes in osteosarcoma

2019 ◽  
Author(s):  
Christopher E. Lietz ◽  
Cassandra Garbutt ◽  
William T. Barry ◽  
Vikram Deshpande ◽  
Yen-Lin Chen ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Prognostic Significance ◽  
Treatment Strategies ◽  
Cox Proportional Hazards ◽  
Molecular Networks ◽  
Future Application ◽  
Treatment Standards ◽  
Novel Therapeutics ◽  
Microrna Profile ◽  
National Cooperative

ABSTRACTBackgroundThere is a lack of well validated biomarkers in osteosarcoma, a rare, recalcitrant disease with variable outcome and poorly understood biologic behavior, for which treatment standards have stalled for decades. The only standard prognostic factor in osteosarcoma remains the amount of pathologic necrosis following pre-operative chemotherapy, which does not adequately capture the biologic complexity of the tumor and has not resulted in optimized patient therapeutic stratification. New, robust biomarkers are needed to understand prognosis and better reflect the underlying biologic and molecular complexity of this disease.MethodsWe performed microRNA sequencing in 74 frozen osteosarcoma biopsy samples, the largest single center translationally analyzed cohort to date, and separately analyzed a multi-omic dataset from a large (n = 95) NCI supported national cooperative group cohort. Molecular patterns were tested for association with outcome and used to identify novel therapeutics for further study by integrative pharmacogenomic analysis.ResultsMicroRNA profiles were found predict Recurrence Free Survival (5-microRNA profile, Median RFS 59 vs 202 months, log rank p=0.06, HR 1.87, 95% CI 0.96-3.66). The profiles were independently prognostic of RFS when controlled for metastatic disease at diagnosis and pathologic necrosis following chemotherapy in multivariate Cox proportional hazards regression (5-microRNA profile, HR 3.31, 95% CI 1.31–8.36, p=0.01). Strong trends for survival discrimination were observed in the independent NCI dataset, and transcriptomic analysis revealed the downstream microRNA regulatory targets are also predictive of survival (median RFS 17 vs 105 months, log rank p=0.007). Additionally, DNA methylation patterns held prognostic significance. Through machine learning based integrative pharmacogenomic analysis, the microRNA biomarkers identify novel therapeutics for further study and stratified application in osteosarcoma.ConclusionsOur results support the existence of molecularly defined phenotypes in osteosarcoma associated with distinct outcome independent of clinicopathologic features. We validated candidate microRNA profiles and their associated molecular networks for prognostic value in multiple independent datasets. These networks may define previously unrecognized osteosarcoma subtypes with distinct molecular context and clinical course potentially appropriate for future application of tailored treatment strategies in different patient subgroups.

Abstract P246: A Naturalistic Assessment of Lipid Treatment Strategies: Further LDL-C Reduction Versus Comprehensive Lipid Management

2011 ◽  
Vol 4 (suppl_2) ◽  
Author(s):  
Robert Simko ◽  
Mark Cziraky ◽  
Ralph Quimbo
Keyword(s):  
Index Date ◽  
Proportional Hazards ◽  
Treatment Strategies ◽  
Geographic Region ◽  
Cox Proportional Hazards ◽  
Health Coverage ◽  
Adverse Cardiovascular Event ◽  
Adjunct Therapy ◽  
Lipid Management ◽  
Lipid Panel

Objective: To compare cardiovascular (CV) outcomes between patients initiating adjunct therapy with either niacin extended-release (NER) for broader lipid panel management or ezetimibe (EZE) for continued LDL-C reduction. Methods: Statin-treated patients aged ≥30 augmenting with NER or EZE between 1/1/05-11/30/09 (Index Date) were identified. Patients with ≥12 months of health plan eligibility before the Index Date (baseline) were included, and patients with secondary risk and ≥1 full lipid panel were retained. A propensity score (PPS) model was developed controlling for the following baseline factors: age, gender, geographic region, type of health coverage, baseline lipids, mode of therapy augmentation, potency of adjunct statin therapy, baseline statin adherence, comorbidities, and alternative CV medications. NER and EZE patients were matched based on PPS. Clinical outcomes included incidence of a major adverse cardiovascular event (MACE). MACE was defined as a composite of acute ischemic heart (IHD), peripheral vascular (PVD), and cerebrovascular disease (CVD) events. The economic outcome was annual CV disease-related costs. These outcomes were compared using univariate Cox proportional hazards and generalized linear models respectively. Results: A total of 15,195 patients initiated adjunct therapy with NER (n=3,098) and EZE (n=12,097) meeting all study criteria. Post-PPS match, 2,261 patients were identified in each cohort with no statistically significant differences in baseline or concurrent treatment characteristics. Frequency of MACE was lower among NER patients (3.5%) vs. EZE (5.4%), with a hazard ratio (HR) of 0.89 (95% CI: 0.67-1.20). Specifically, NER patients demonstrated a lower risk of IHD (HR: 0.90; 95% CI: 0.65-1.25) and CVD (HR: 0.69; 95% CI: 0.34-1.41) events vs. EZE patients. These findings correspond to significantly lower adjusted annual cost among NER patients ($8,168; 95% CI: $7,720 - $8,641) vs. EZE ($9,030; 95% CI: $8,535 - $9,553) ( P= 0.0136). Conclusions: Positive clinical benefits observed in this broader naturalistic population are consistent with results from recent clinical trials and suggest that treating beyond LDL-C with statin + NER in secondary risk patients may reduce CV risk and associated costs.

Trifluridine/tipiracil (FTD/TPI) and regorafenib (REG) in patients with metastatic colorectal cancer (mCRC): A single institution retrospective study.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 592-592 ◽  
Author(s):  
Anuj K. Patel ◽  
Kimmie Ng ◽  
Mei Sheng Duh ◽  
Victoria E. Barghout ◽  
Lynn Huynh ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cancer Center ◽  
Single Institution ◽  
Primary Tumors ◽  
Therapy Initiation ◽  
Cox Proportional Hazards Models ◽  
Baseline Characteristics ◽  
Dose Modifications ◽  
Effectiveness Data

592 Background: FTD/TPI and REG have both demonstrated prolonged survival in refractory mCRC patients (pts) when compared to placebo but limited comparative effectiveness data are available. This study aims to compare outcomes following initiation of FTD/TPI or REG for mCRC at a single academic cancer center. Methods: Retrospective chart reviews were conducted in all pts with mCRC who initiated FTD/TPI or REG between 2012-2017. Analyses of time from index therapy initiation to discontinuation for any reason (TTD), real-world response rates (rwRR) and disease control rates (rwDCR) were performed. Cox proportional hazards models adjusting for demographic and clinical characteristics were performed for overall survival (OS). Results: 126 FTD/TPI and 95 REG pts were included. Baseline characteristics were similar in both groups, though more pts treated with FTD/TPI had right-sided primary tumors compared to REG (30.4% vs. 25.5%, p = 0.43). Treatment patterns pre- and post-index therapy were comparable in both groups. Median observation duration for FTD/TPI and REG was 7.1 and 6.3 months, respectively. Mean TTD was 88.4 days for FTD/TPI pts and 84.2 days for REG pts (p = 0.42). Fewer pts treated with FTD/TPI discontinued due to toxicities than pts treated with REG (8.2% vs. 24.2%, p = 0.001). A higher proportion of FTD/TPI pts had no dose modifications vs. REG pts (84.0% vs. 64.1%, p < 0.001). OS was similar between the two groups (adjusted hazard ratio [HR] FTD/TPI vs. REG: 0.79, p = 0.13). FTD/TPI pts had higher rwRR (52.5% vs. 34.2%, p = 0.01) and rwDCR (64.2% vs. 46.1%, p = 0.01) than REG pts. In the subgroup of pts ≥ 65 years, mean TTD was higher in FTD/TPI pts (105.9 vs. 77.6 days, p = 0.004). Pts ≥ 65 years receiving FTD/TPI had better OS than REG pts (HR: 0.51, p = 0.03). Conclusions: In this single institution study, TTD and OS were similar between pts treated with FTD/TPI and REG. Fewer pts treated with FTD/TPI than REG discontinued due to toxicities or required dose modification. Reported responses rates were higher in FTD/TPI pts. Older pts (≥ 65 years) on FTD/TPI remained on treatment longer and had better OS than REG pts.

scholarly journals Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome

2020 ◽  
Vol 79 (10) ◽  
pp. 1286-1289 ◽  
Author(s):  
Mirko Scarsi ◽  
Silvia Piantoni ◽  
Enrico Colombo ◽  
Paolo Airó ◽  
Donata Richini ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Colchicine Treatment ◽  
Serum Levels ◽  
Potential Interaction ◽  
Cox Proportional Hazards ◽  
The Public ◽  
Risk Of Death ◽  
Hospitalised Patients

ObjectivesThe outbreak of COVID-19 posed the issue of urgently identifying treatment strategies. Colchicine was considered for this purpose based on well-recognised anti-inflammatory effects and potential antiviral properties. In the present study, colchicine was proposed to patients with COVID-19, and its effects compared with ‘standard-of-care’ (SoC).MethodsIn the public hospital of Esine, northern Italy, 140 consecutive inpatients, with virologically and radiographically confirmed COVID-19 admitted in the period 5–19 March 2020, were treated with ‘SoC’ (hydroxychloroquine and/or intravenous dexamethasone; and/or lopinavir/ritonavir). They were compared with 122 consecutive inpatients, admitted between 19 March and 5 April 2020, treated with colchicine (1 mg/day) and SoC (antiviral drugs were stopped before colchicine, due to potential interaction).ResultsPatients treated with colchicine had a better survival rate as compared with SoC at 21 days of follow-up (84.2% (SE=3.3%) vs 63.6% (SE=4.1%), p=0.001). Cox proportional hazards regression survival analysis showed that a lower risk of death was independently associated with colchicine treatment (HR=0.151 (95% CI 0.062 to 0.368), p<0.0001), whereas older age, worse PaO2/FiO2, and higher serum levels of ferritin at entry were associated with a higher risk.ConclusionThis proof-of-concept study may support the rationale of use of colchicine for the treatment of COVID-19. Efficacy and safety must be determined in controlled clinical trials.

scholarly journals Discontinuation of Azathioprine Could Be Considered in Pediatric Patients with Crohn’s Disease who Have Sustained Clinical and Deep Remission

2021 ◽  
Author(s):  
Tae Jong Jeong ◽  
Eun Sil Kim ◽  
Yiyoung Kwon ◽  
Seonwoo Kim ◽  
Sang Won Seo ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Combination Therapy ◽  
Pediatric Patients ◽  
Proportional Hazards ◽  
Treatment Strategies ◽  
Cox Proportional Hazards ◽  
Clinical Relapse ◽  
Factors Affecting ◽  
Factors Associated

Abstract Few studies have demonstrated treatment strategies about the duration and cessation of medications in patients with Crohn’s disease (CD). We investigated factors affecting clinical relapse after infliximab (IFX) or azathioprine (AZA) withdrawal in pediatric patients with CD on combination therapy. Pediatric patients with moderate-to-severe CD receiving combination therapy were analyzed retrospectively and factors associated with clinical relapse were investigated. Discontinuation of IFX or AZA was performed in patients who sustained clinical remission (CR) for at least two years and achieved deep remission. A total of 75 patients were included. Forty-four patients (58.7%) continued with combination therapy and 31 patients (41.3%) discontinued AZA or IFX (AZA withdrawal 10, IFX withdrawal 15, both withdrawal 6). Cox proportional-hazards regression identified four factors associated with clinical relapse: IFX cessation (hazard ratio; HR 2.982, P=0.0081), formation of antibody-to-IFX (ATI) (HR=3.12, P=0.0373), IFX trough level (TL) (HR=0.581, P=0.003) and 6-thioguanine nucleotide (6-TGN) level (HR=0.978, P<0.001). However, AZA cessation was not associated with clinical relapse (P=0.9021). Even when applied in pediatric patients who meet stringent criteria, IFX cessation increased the relapse risk. However, withdrawal of AZA could be contemplated in pediatric patients with CD who have sustained CR for at least two years and achieved deep remission.

scholarly journals Genetic Polymorphisms of Long Non-coding RNA Linc00312 Are Associated With Susceptibility and Predict Poor Survival of Nasopharyngeal Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhen Guo ◽  
Mei-Hua Bao ◽  
Yun-Xia Fan ◽  
Yan Zhang ◽  
Hai-Yan Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Nasopharyngeal Carcinoma ◽  
Secondary Structure ◽  
Genetic Polymorphisms ◽  
Proportional Hazards ◽  
Multivariate Logistic Regression Analysis ◽  
Cox Proportional Hazards ◽  
Luciferase Reporter ◽  
Candidate Snps ◽  
Nucleotide Polymorphisms

BackgroundLinc00312 is dysregulated in nasopharyngeal carcinoma (NPC) and participates in the initiation and progression of NPC. Our previous studies suggested that linc00312 was able to enhance the sensitivity of NPC cells to irradiation and NPC patients with higher expression of linc00312 was associated with better short-term curative effect and overall survival. The single nucleotide polymorphisms (SNPs) of lncRNAs may influence the disease course and outcome by affecting the expression, secondary structure or function of lncRNAs. However, the role of SNPs in linc00312 on the occurrence and survival of NPC remains unknown.MethodsWe recruited 684 NPC patients and 823 healthy controls to evaluate the association between linc00312 SNPs and NPC susceptibility by using multivariate logistic regression analysis. Kaplan-Meier analysis and Cox proportional hazards regression were applied to assess the effect of linc00312 SNPs on the survival of NPC patients. The relative expression of linc00312 in NPC tissues was determined by real-time PCR. The interaction between linc00312 and mir-411-3p was explored by luciferase reporter assay. In silico prediction of the changes on linc00312 folding structure was conducted by RNAfold WebServer.ResultWe demonstrated that rs12497104 (G &gt; A) GA genotype carriers had a higher risk than others for suffering from NPC (GA vs GG, OR = 1.437, P = 0.003). Besides, patients with rs12497104 AA genotype showed a poorer overall survival in contrast to GG genotype (AA vs GG, HR = 2.117, P = 0.011). In addition, the heterozygous carriers of rs15734 (G &gt; A) and rs164966 (A &gt; G) were correlated with decreased risk of NPC (GA vs GG, OR = 0.778, P = 0.031; GA vs AA, OR = 0.781, P = 0.033, respectively). We found that the three SNPs might influence the expression of linc00312 in a genotype specific feature. The local centroid secondary structure as well as the minimum free energy of linc00312 were changed following the candidate SNPs alterations. Besides, we revealed that the G to A alteration at rs12497104 disrupted the binding between mir-411-3p and linc00312.ConclusionOur results indicated genetic polymorphisms of linc00312 might serve as potential biomarkers for NPC carcinogenesis and prognosis.

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