scholarly journals P654 Influence of the interval of time between anti-TNF and vedolizumab or ustekinumab in the response to treatment in patients with inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S539-S539
Author(s):  
I Bastón Rey ◽  
M Costa ◽  
C Calviño-Suarez ◽  
V Mauriz-Barreiro ◽  
D De la Iglesia ◽  
...  

Abstract Background There is no evidence about the time that it is reasonable to wait until starting Vedolizumab (VDZ) or Ustekinumab (UST) in case of loss of response to anti-TNF therapy. The aim of our study was to evaluate whether the time between the change from any anti-TNF drug to VDZ or UST had an influence on the risk of treatment failure and the rate of adverse events or severe infections. Methods A retrospective, observational single-centre study was designed. Inclusion criteria were all adult patients with moderate-to-severe IBD who started treatment with VDZ or UST due to loss of response to anti-TNF (Infliximab or Adalimumab). Exclusion criteria were patients who had received treatment for different indications such as prevention of recurrence or extra-intestinal manifestations. Patients that changed directly from VDZ to UST or from UST to VDZ were also excluded. We defined two groups of periods based on the interval of time between the last dose of anti-TNF and the first dose of VDZ or UST: Group A: early (≤30 days), Group B: late (31–60 days). Patients that had a waiting time of over 60 days were also excluded. Treatment failure after the initiation of VDZ or UST was defined as the need for dose intensification, surgical resection, therapy removal for ineffectiveness or adverse reaction. The existence of infections was also evaluated. Results are shown as percentages, median, range and Hazard Ratio (CI 95%). Fisher test and Cox Regression analysis were also performed. Results 46 patients (45.6% CD) were consecutively included (mean age 47.6 years). 17 had initially been treated with Infliximab and 29 with Adalimumab. Thirty patients were changed to VDZ and 16 to UST. Twenty-three patients were included in Group A and 23 in Group B. Treatment failure was observed in 20 patients: 9/23 in group A and 11/23 in group B with a mean follow-up of 323 days (range 152–432). The duration of the interval of time between stopping anti-TNF and starting VDZ or UST was not associated with increased risk of treatment failure (p = 0.25) with a median of time until loss of response of 252 days (range 98–432 days) in Group A and 168 days (range 131–418 days) in group B (Figure 1). No differences were found between patients with CD or UC (p = 0.23) and no differences were found in starting with VDZ or UST. There was 1 adverse event that forced a stopping of treatment in group A. No infections that required hospitalisation were observed. Conclusion The interval of time between anti-TNF and VDZ or UST had no influence on the rates of treatment failure, adverse events or infections in our cohort.

2018 ◽  
Vol 12 (7) ◽  
pp. 804-810 ◽  
Author(s):  
Konstantinos Papamichael ◽  
Ravy K Vajravelu ◽  
Byron P Vaughn ◽  
Mark T Osterman ◽  
Adam S Cheifetz

Abstract Background and Aims Reactive testing has emerged as the new standard of care for managing loss of response to infliximab in inflammatory bowel disease [IBD]. Recent data suggest that proactive infliximab monitoring is associated with better therapeutic outcomes in IBD. Nevertheless, there are no data regarding the clinical utility of proactive infliximab monitoring after first reactive testing. We aimed to evaluate long-term outcomes of proactive infliximab monitoring following reactive testing compared with reactive testing alone in patients with IBD. Methods This was a retrospective multicenter cohort study of consecutive IBD patients on infliximab maintenance therapy receiving a first reactive testing between September 2006 and January 2015. Patients were divided into two groups; Group A [proactive infliximab monitoring after reactive testing] and Group B [reactive testing alone]. Patients were followed through December 2015. Time-to-event analysis for treatment failure and IBD-related surgery and hospitalization was performed. Treatment failure was defined as drug discontinuation due to either loss of response or serious adverse event. Results The study population consisted of 102 [n = 70, 69% with CD] patients [Group A, n = 33 and Group B, n = 69] who were followed for (median, interquartile range [IQR]) 2.7 [1.4–3.8] years. Multiple Cox regression analysis identified proactive following reactive TDM as independently associated with less treatment failure (hazard ratio [HR] 0.15; 95% confidence interval [CI] 0.05–0.51; p = 0.002) and fewer IBD-related hospitalizations [HR: 0.18; 95% CI 0.05–0.99; p = 0.007]. Conclusions This study showed that proactive infliximab monitoring following reactive testing was associated with greater drug persistence and fewer IBD-related hospitalizations than reactive testing alone.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Reza Hekmat

Background. Impact of hemodialysis adequacy on patient survival is extensively studied. The current study compares the survival of chronic hemodialyzed, undocumented, uninsured, Afghan immigrant patients with that of a group of insured Iranian patients matched for underlying disease, age, weight, level of education, marital status, income, and number of comorbid conditions. Methods. Eighty chronic hemodialysis patients (mean age 42.8 ± 10.5 years) entered this historical cohort study in Mashhad, Iran, between January 2012 and January 2015. Half of the patients were undocumented, uninsured, Afghan immigrants (Group A) matched with forty insured Iranian patients (Group B). To compare the survival rate of the two patient groups, Kaplan–Meir survival analysis test was used. Results. Group A patients were underdialyzed with a weekly Kt/V which was significantly less in comparison with that of Group B (1.63 ± 0.63 versus 2.54 ± 0.12, p value = 0.01). While Group A’s number of hemodialysis sessions per week was fewer than that of Group B (1.45 ± 0.56 versus 2.8 ± 0.41, p value = 0.04), the mean of Kt/V in each hemodialysis session was higher in them, in comparison with Group B (1.43 ± 0.25 versus 1.3 ± 0.07, p value = 0.045). In Group B and Group A patients, one-year survival was 70% versus 50%, two-year survival was 55% versus 30%, and three-year survival was 40% versus 20%, respectively (p values = 0.04, 0.02 and 0.04, respectively). In Cox regression analysis, hemodialysis adequacy and uninsurance were factors impacting patients’ survival (OR = 1.193 and 0.333, respectively). Conclusions. Undocumented, uninsured, inadequately hemodialyzed, Afghan patients had a significantly lower one-, two-, and three-year survival as opposed to their Iranian counterparts, probably due to lack of insurance.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marios Theodoridis ◽  
Stylianos Panagoutsos ◽  
Ioannis Neofytou ◽  
Konstantia Kantartzi ◽  
Efthimia Mourvati ◽  
...  

Abstract Background and Aims Peritoneal protein loss (PPL) through peritoneal effluent has been a well-recognized detrimental result of peritoneal dialysis (PD). The amount of protein lost will depend on dialysis time, protein size, its serum concentration and other factors including patients’ clinical status. Peritoneal protein loss may be a manifestation of endothelial dysfunction, as with another type of capillary protein leakage, microalbuminuria, a recognized endothelial dysfunction marker. The aim of this study was to retrospectively evaluate the influence of PPL on cardiovascular mortality of peritoneal dialysis patients Method This is a single center retrospective study of 84 PD patients (m=54, f=30) with mean age of 65.2±17 years, mean PD duration of 43.2±24.9 months conducted for the time period from 2006 to 2019 (13 years). The patients were divided into two groups according to the amount of protein excreted during the modified Peritoneal Equilibration Test (PET) procedure using PD solution of 3.86% DW, 2 Lt infusion volume for total time of 4 hours. The total amount of proteins excreted was calculate from PET by multiplying the concentration of proteins at the end of the test with the total volume of PD fluid at the same time. Group A excreted a total amount of proteins < 1.55 gr (median value) at the end of PET test and Group B > 1.55 gr. The cumulative all-cause and cardiovascular survival of the PD patients was calculated by Kaplan Meier while the possible effect of any parameter in survival rates was evaluated by using Cox Regression analysis Results There was not any statistically significant difference between the two groups according to PD duration, age, dialysis adequacy targets, Residual Renal Function(RRF), BMI, ultrafiltration volume during PET and their transport status. The cumulative all-cause survival using Kaplan-Meier analysis revealed no statistically significant deference between the two groups (Log Rank p=0.55) even though mortality risk was adjusted for several factors (Cox Regression). When cardiovascular survival, using Cox Regression analysis, was adjusted for age, sex, Diabetes, PD modality, dialysis Kt/V and RRF we found that Group A (with protein excretion < 1.55 gr) had statistically significant better cardiovascular survival (p=0.029) compared to Group B. We confirm these results while trying to find among the total of our patients the possible risk factors for cardiovascular mortality. Using Cox Regression analysis, the amount of protein excreted during PET procedure and the type of PD solutions (high or low in GDPs) used were statistically significant (p=0.019 and p=0.04 respectively) independent risk factors for cardiovascular survival in our patients. Conclusion These results indicate that protein loss during peritoneal dialysis procedure has negative impact on cardiovascular mortality and survival of PD patients. Additionally, the use of PD solutions with low Glucose Degradation Products (GDPs) and AGEs may improve PD patient’s cardiovascular survival. Randomized interventional studies are encouraged to address the pathological concern of PPL in the future, namely its effects on cardiovascular conditions or its role as marker and effort to reduce PPL using ACE inhibitors or vit D should be considered only if it diminishes cardiovascular morbidity or mortality.


2021 ◽  
Author(s):  
Giuliana Scarpati ◽  
Daniela Baldassarre ◽  
Graziella Lacava ◽  
Filomena Oliva ◽  
Gabriele Pascale ◽  
...  

Rationale Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Elevated circulating levels of KL-6 may denote disorder of the alveolar epithelial lining. Objective Aim of this study was to verify if KL-6 values may help to risk stratify and triage severe COVID-19 patients. Methods We performed a retrospective prognostic study on 110 COVID-19 ICU patients, evaluating the predictive role of KL-6 for mortality. Measurements and Main Results The study sample was divided in two groups related according to the median KL-6 value [Group A (KL-6 lower than the log-transformed median (6.73)) and Group B (KL-6 higher than the log-transformed median)]. In both linear and logistic multivariate analyses, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (P/F) was significantly and inversely related to KL-6. Death rate was higher in group B than in group A (80.3 versus 45.9%) (p<0.001), Accordingly, the Cox regression analysis showed a significant prognostic role of KL-6 on mortality in the whole sample as well as in the subgroup with SOFA lower than its median value. Conclusions At ICU admission, KL-6 serum level was significantly lower in the survivors group. Our findings shown that, in severe COVID19 patients, elevated KL-6 was strongly associated with mortality in ICU.


2009 ◽  
Vol 37 (1) ◽  
pp. 182-189 ◽  
Author(s):  
OGUZ SOYLEMEZOGLU ◽  
MUSTAFA ARGA ◽  
KIBRIYA FIDAN ◽  
SEVIM GONEN ◽  
HAMDI CIHAN EMEKSIZ ◽  
...  

Objective.More than 50 disease-associated mutations of the Mediterranean fever gene (MEFV) have been identified in familial Mediterranean fever (FMF), some of which were shown to have different clinical, diagnostic, prognostic, and therapeutic implications. The aim of our study was to define the frequency of mutation type, genotype-phenotype correlation, and response to colchicine treatment in patients with FMF.Methods.This study included 222 pediatric FMF patients. All patients were investigated for 6 MEFV mutations. Then patients were divided into 3 groups according to the presence of M694V mutation on both of the alleles (homozygotes), on only 1 allele (heterozygotes), and on none of the alleles, and compared according to their phenotypic characteristics and response to treatment. M694V/M694V was denoted Group A, M694V/Other Group B, and Other/Other, Group C.Results.Complete colchicine response was significantly lower while the rate of unresponsiveness was significantly higher in Group A compared to Groups B and C (p = 0.031, p < 0.001 and p = 0.005, p = 0.029, respectively). No differences except proteinuria were found between the phenotypic features of 3 groups. Group C had the lowest rate of proteinuria development (p = 0.024). All the amyloidosis patients were in Group A.Conclusion.Our results indicate that the M694V/M694V mutation is associated with lower response to colchicine treatment. Therefore, patients homozygous for M694V/M694V may be carrying an increased risk for development of amyloidosis.


2019 ◽  
Vol 130 (5) ◽  
pp. 1710-1720 ◽  
Author(s):  
Yasushi Motoyama ◽  
Tsukasa Nakajima ◽  
Yoshiaki Takamura ◽  
Tsutomu Nakazawa ◽  
Daisuke Wajima ◽  
...  

OBJECTIVELumbar spinal drainage (LSD) during neurosurgery can have an important effect by facilitating a smooth procedure when needed. However, LSD is quite invasive, and the pathology of brain herniation associated with LSD has become known recently. The objective of this study was to determine the risk of postoperative brain herniation after craniotomy with LSD in neurosurgery overall.METHODSIncluded were 239 patients who underwent craniotomy with LSD for various types of neurological diseases between January 2007 and December 2016. The authors performed propensity score matching to establish a proper control group taken from among 1424 patients who underwent craniotomy and met the inclusion criteria during the same period. The incidences of postoperative brain herniation between the patients who underwent craniotomy with LSD (group A, n = 239) and the matched patients who underwent craniotomy without LSD (group B, n = 239) were compared.RESULTSBrain herniation was observed in 24 patients in group A and 8 patients in group B (OR 3.21, 95% CI 1.36–8.46, p = 0.005), but the rate of favorable outcomes was higher in group A (OR 1.79, 95% CI 1.18–2.76, p = 0.005). Of the 24 patients, 18 had uncal herniation, 5 had central herniation, and 1 had uncal and subfalcine herniation; 8 patients with other than subarachnoid hemorrhage were included. Significant differences in the rates of deep approach (OR 5.12, 95% CI 1.8–14.5, p = 0.002) and temporal craniotomy (OR 10.2, 95% CI 2.3–44.8, p = 0.002) were found between the 2 subgroups (those with and those without herniation) in group A. In 5 patients, brain herniation proceeded even after external decompression (ED). Cox regression analysis revealed that the risk of brain herniation related to LSD increased with ED (hazard ratio 3.326, 95% CI 1.491–7.422, p < 0.001). Among all 1424 patients, ED resulted in progression or deterioration of brain herniation more frequently in those who underwent LSD than it did in those who did not undergo LSD (OR 9.127, 95% CI 1.82–62.1, p = 0.004).CONCLUSIONSBrain herniation downward to the tentorial hiatus is more likely to occur after craniotomy with LSD than after craniotomy without LSD. Using a deep approach and craniotomy involving the temporal areas are risk factors for brain herniation related to LSD. Additional ED would aggravate brain herniation after LSD. The risk of brain herniation after placement of a lumbar spinal drain during neurosurgery must be considered even when LSD is essential.


2010 ◽  
Vol 54 (7) ◽  
pp. 612-619 ◽  
Author(s):  
Natália António ◽  
Francisco Soares ◽  
Carolina Lourenço ◽  
Fátima Saraiva ◽  
Francisco Gonçalves ◽  
...  

OBJECTIVE: To determine whether previous insulin treatment independently influences subsequent outcomes in diabetic patients with ACS (acute coronary syndromes). SUBJECTS AND METHODS: 375 diabetic patients with ACS, divided in 2 groups: Group A (n = 69) - previous insulin and Group B (n = 306) - without previous insulin. Predictors of 1-year mortality and major adverse cardiac events (MACE) were analyzed by Cox regression analysis. RESULTS: Group A had more previous stroke (17.4% vs. 9.2%, p = 0.047) and peripheral artery disease (13.0% vs. 3.6%, p = 0.005). They had significantly higher admission glycemia and lower LDL cholesterol. There were no significant differences in the type of ACS, in 1-year mortality (18.2% vs. 10.4%, p = 0.103) or MACE (32.1% vs. 23.0%, p = 0.146) between groups. In multivariate analysis, insulin treatment was neither an independent predictor of 1-year mortality nor of MACE. CONCLUSION: Despite the more advanced atherosclerotic disease, diabetics under insulin had similar outcomes to those without insulin. Insulin may protect diabetics from the expected poor adverse outcome of an advanced atherosclerotic disease.


PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0249590
Author(s):  
Amjad Alharbi ◽  
Haifa Bin Dokhi ◽  
Ghadir Almuhaini ◽  
Futoon Alomran ◽  
Emad Masuadi ◽  
...  

Objectives KRAS, NRAS, and BRAF mutations are commonly present in colorectal cancer (CRC). We estimated the frequency of KRAS, NRAS, and BRAF mutations and assessed their impact on survival and other clinical variables among Saudi patients. Design Retrospective cohort study design. Settings Oncology department of a tertiary hospital in Riyadh, Saudi Arabia. We gathered information from 2016 to 2018. Participants Cohort of 248 CRC patients to assess the demographic data, pathological tumour features, response to treatment modalities, disease progression, and metastasis. Statistical analysis used Correlation analysis using the chi-square test. Survival analysis using a Kaplan Meier method. Cox regression analysis to calculate the hazard ratios. Results Demographic data revealed that 84% of patients were diagnosed with CRC above the age of 50 years. Only 27% of patients presented with distant metastasis. KRAS mutations were the most prevalent (49.6%), followed by NRAS mutations (2%) and BRAF mutations (0.4%). Wild type tumours were found among 44.4% of patients. KRAS mutation showed no significant correlation with the site, type, pathological grade, and stage of the tumour. The mean survival time was shorter among patients with KRAS mutations than among patients with wild type KRAS tumours (54.46 vs. 58.02 months). Adjusted analysis showed that the survival time was significantly affected by patients’ age at diagnosis (P = 0.04). Male patients had an increased risk of mortality by 77% (hazard ratio: 1.77). Conclusions Saudi CRC patients had a high frequency of KRAS mutations and a low frequency of BRAF mutations. The KRAS mutation status did not affect the patients’ survival.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18061-18061
Author(s):  
V. Mutri ◽  
C. Pinto ◽  
A. Marino ◽  
M. Di Bisceglie ◽  
D. Dell’Amore ◽  
...  

18061 Background: The aim of this study is to evaluate the impact on survival of preoperative chemotherapy in potentially resectable MPM and correlations with prognostic factors. Methods: The eligibility criteria were: histologically MPM, stage T1–3N0–2M0, age =75 years, KPS = 80, adequate organ function. A first group of pts (group A) received cisplatin 75 mg/m2 d1 and gemcitabine 1,200 mg/m2 d1,8, every 3 weeks for 4 courses, followed by EPP and by 6 courses of adjuvant chemotherapy with mitoxantrone 10 mg/m2 d1, methotrexate 35 mg/m2 d1 and mitomycin 7 mg/m2 d1, every 3 weeks with mitomycin in alternate cycles. A second group of pts (group B) received cisplatin 75 mg/m2 d1 plus pemetrexed 500 mg/m2 d1 for 4 cycles. In each group, only those pts with metastatic lymph nodes and/or positive resection margins received radiotherapy after EPP. The prognostic factors evaluated were: sex, histotype, stage at diagnosis, clinical objective response. Results: Between February 2000 and December 2006, 32 pts were enrolled (8 group A, 24 group B). Pt characteristics were: 27M (84.4%), 5F (15.6%), median age 64 years (51–72), median KPS 100 (80–100), histological subtype: 27 (84.4%) epithelial, 2 (6.3%) sarcomatous, 3 (9.4%) mixed; IMIG stage: 6 (18.8%) I, 16 (50%) II, 10 (31.2%) III. The clinical response to neoadjuvant chemotherapy was: 10 (31.3%) CR + PR, 16 (50%) SD and 6 (18.7%) PD. Eighteen (56.3%) pts underwent EPP. In the 14 pts who did not undergo EPP: 5 (15.6%) were treated with pleurectomy and 9 (28.1%) were not treated with surgery. Two postoperative deaths (1 contralateral pneumonia and 1 ARDS) occurred after EPP. No pts were treated with radiotherapy after EPP. The estimated median overall survival, 1-year and 2-year survival rates in the pts treated with EPP and not treated with EPP were 20 and 12 months (p=0.468), 60 and 41%, 42 and 20%, respectively. In the multivariate analysis (Cox regression analysis), none of evaluated prognostic factors was significantly associated with an improved OS. Conclusions: These data show that preoperative chemotherapy followed by EPP is a feasible approach, while initial analysis suggests favourable survival. No significant prognostic factors were identified. No significant financial relationships to disclose.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S420-S422
Author(s):  
R Mahmoud ◽  
J Schultheiss ◽  
J Louwers ◽  
M van der Kaaij ◽  
B van Hellemondt ◽  
...  

Abstract Background Globally, the prevalences of both inflammatory bowel diseases (IBD) and obesity have increased over the past decades. Recently, obesity has been linked to treatment failure in anti-TNF-treated patients with inflammatory bowel disease (IBD). We assessed whether obesity was associated with an increased risk of treatment failure and immunogenicity (i.e. anti-drug antibodies) among IBD patients treated with adalimumab (ADA) or infliximab (IFX). Methods This was a multicenter, retrospective cohort study of adult patients with IBD, treated with ADA or IFX for at least four months between 2011-2019 at a general hospital or a tertiary referral center. Obesity was defined as body mass index (BMI) &gt;30kg/m2. Adjusted hazard rates (aHR) were calculated by mixed-effects Cox regression analysis, accounting for multiple treatment episodes in individual patients and adjusted for sex, prior anti-TNF exposure, immunomodulator use, IBD phenotype (ulcerative colitis versus Crohn’s disease), age, disease duration, smoking and rheumatological comorbidity. Multiple imputation was used to replace missing values (5% for BMI). Results We included 728 patients, providing 2339 patient-years of follow-up and 868 treatment episodes with anti-TNF; 130 (17.9%) patients were obese. Obesity was associated with female sex (67% vs 54%), smoking (36% vs 22%), older age (median 42 vs 36 years) and prior exposure to methotrexate (25% vs 15%). In patients receiving ADA, obesity was significantly and independently associated with a higher risk of immunogenicity (Figure 1a, aHR: 2.15, 95%CI: 1.10 – 4.19) and treatment failure (Figure 2a), although significance of the latter association was lost after correcting for relevant confounders (aHR: 1.33, 95%CI: 0.87 – 2.03). In patients treated with IFX, obesity was not associated with immunogenicity (Figure 1b, aHR: 1.05, 95%CI: 0.54 – 2.03) or treatment failure (Figure 2b, aHR: 0.98, 95%CI: 0.70 – 1.39). Trough levels were significantly lower in obese patients treated with ADA, but not IFX. Conclusion In patients treated with ADA, but not IFX, obesity is associated with immunogenicity and possibly a higher risk of treatment failure. Proactive therapeutic drug monitoring may be warranted in obese patients treated with ADA.


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