Abstract
Background
Primary aim: To assess the durability of ustekinumab treatment in patients with ulcerative colitis (UC). Secondary aims: To assess the short-term effectiveness, the durability of ...response, and the tolerability of ustekinumab in clinical practice.
Methods
Retrospective, multicenter study including UC patients who had received the 1st ustekinumab dose at least 16 weeks before inclusion. Patients were followed-up from the 1st ustekinumab dose to treatment discontinuation or last visit. Only patients with active disease Partial Mayo Score (PMS)>2 at ustekinumab start were considered in the effectiveness analysis. Clinical effectiveness was based on PMS. Patients who stopped ustekinumab before their last visit were considered not in remission at subsequent time points (negative imputation).
Results
620 patients were included (table 1). 78% of patients who started ustekinumab maintenance treatment, did it with 90 mg every-8-weeks dose. 155 patients (25%) withdrew ustekinumab during follow-up median=12 months (m). Incidence rate of ustekinumab discontinuation was 20% per patient-year of follow-up. The probability of maintaining ustekinumab is shown in figure 1A. Among patients who withdrew ustekinumab, the main reasons were primary non-response (39%) and loss of response (35%). Anaemia at baseline (HR=1.5, 95%CI=1.1-2.1), steroids at baseline (HR=1.5; 95%CI=1.06-2.08), and more severe clinical activity at baseline (HR=1.5; 95%CI=1.09-2.06) were associated with higher risk of ustekinumab discontinuation. Short and long-term effectiveness of ustekinumab is shown on figure 1B. Moderate-severe vs. mild disease activity at baseline (OR=0.3, 95%CI=0.2-0.5), male sex (OR=0.5; 95%CI=0.4-0.8), and increased number of previous biologics (OR=0.6, 95%CI=0.6-0.8) were associated with lower likelihood of steroid-free remission at week 16. A total of 57 (25%) patients among those with active disease at baseline and with steroid-free remission at week 16, lost response during a median follow-up of 8 m (IQR=3-16 m) (figure 1C). The dose was escalated in 72% of patients with loss of response, and 80% improved (67% remission); an intravenous reinduction was given in 3 patients, and none of them improved. A total of 176 patients (28%) had at least one adverse event, with infections being the most frequent (11%). No negative impact on extraintestinal manifestations and/or immunomediated diseases was seen.
Conclusion
Ustekinumab was effective in inducing remission even in highly refractory UC patients. A proportion of patients discontinue the treatment, mostly due to primary failure and loss of response. Dose escalation may be effective to regain response after loss of effectiveness. The safety profile was similar to previously reported.
The kinetics of 1,3‐dipolar cycloaddition involving azomethine ylides, generated from thermal 1,2‐prototropy of the corresponding imino ester, employing differential scanning calorimetry (DSC), is ...surveyed. Glycine and phenylalanine derived imino esters have different behavior. The first one prefers reacting with itself at 75 °C, rather than with the dipolarophile. However, the α‐substituted imino ester gives the cycloadduct at higher temperatures. Thermal dynamic analysis, by using 1H NMR spectroscopy, of the neat reaction mixture of the glycine derivative reveals the presence of signals corresponding to the dipole in small abundance. The non‐isothermal and isothermal DSC curves of the cycloaddition of phenylalaninate and diisobutyl fumarate are obtained from freshly prepared samples. The application of known kinetic models and mathematical multiple non‐linear regressions (NLR) allow the determintion and comparison of Ea, lnA, reaction orders, and reaction enthalpy values. Finally a rate equation for each different temperature studied can be established for this particular thermal cycloaddition.
The kinetics of the title cycloaddition has been evaluated through differential scanning calorimetry (DSC; see scheme, Bn=benzyl).The application of known kinetic models and mathematical multiple non‐linear regressions allow the determination and comparison of Ea, lnA, reaction orders, and reaction enthalpy values. Finally a rate equation for each temperature studied can be established for this particular thermal cycloaddition.
Abstract
Background
Thiopurines are the treatment of choice for the prevention of postoperative recurrence (POR) in Crohn’s disease (CD) in high-risk patients, whereas those at low risk should be ...monitored and treated only in case POR occurs. Endoscopic assessment of POR is recommended within the first year following surgery in all patients. With this strategy, more than 50% of patients will develop POR within 6–12 months after surgery. In patients with established POR, anti-TNF agents may be of benefit, but scarce data on this are available.
Methods
Retrospective, multicentre, nationwide study in CD patients who received therapy with anti-TNF agents because of established POR as defined by a Rutgeerts endoscopic score >i1. Epidemiological, clinical, biological and endoscopic features were collected before and after starting anti-TNF. Endoscopic improvement and remission were defined by a reduction in the baseline Rutgeerts score and by a score <i2, respectively. Clinical POR was defined by the presence of two out of the following three criteria: weight loss, increase in stool frequency, and new onset of abdominal pain, in the setting of POR at endoscopy or MRI enterography.
Results
145 CD patients treated with infliximab (69) or adalimumab (76) because of established POR (60% in combination with immunosuppressants) were included. Mean follow-up on anti-TNF: 47 ± 31 months. Table 1 summarises the baseline characteristics.
Baseline characteristics.
Overall (n = 145)
Infliximab (n = 69)
Adalimumab (n = 76)
p
Male sex
72 (50)
41 (59)
41 (59)
0.02
B3 behaviour
50 (30)
25 (36)
25 (33)
0.67
Perianal disease
32 (22)
19 (27)
13 (17)
0.13
Previous intestinal resections
33 (23)
14 (20)
19 (25)
0.49
Active smokers
63 (43)
33 (48)
30 (39)
0.31
Anti-TNF prior to surgery
56 (39)
24 (35)
32 (42)
0.40
Preventive thiopurines for POR
69 (48)
33 (48)
36 (47)
0.95
Rutgeerts score >i2 at anti-TNF start
88 (61)
40 (58)
48 (63)
0.52
Clinical POR at anti-TNF start
44 (30)
23 (33)
21 (28)
0.45
Rates of endoscopic improvement and remission (available in 90 patients; 45 with each anti-TNF. Mean time to endoscopic assessment: 21 ± 22 months), development of clinical POR and surgical POR are shown in Table 2.
Post-anti-TNF outcomes.
Overall
Infliximab
Adalimumab
p
Endoscopic improvement
56 (62)
33 (73)
23 (51)
0.003
Endoscopic remission
40 (44)
27 (60)
13 (29)
0.003
Clinical remission (among patients with baseline clinical POR)
31 (70)
15 (65)
16 (76)
0.92
Development of clinical POR during follow-up
11 (8)
3 (4)
8 (6)
0.16
Surgical POR
12 (9)
6 (9)
6 (8)
0.81
Multivariate logistic regression analysis showed that infliximab therapy (OR 3.9 95% CI 1.3–11.6), combination thiopurine therapy (OR 4.5 95% CI 1.5–15), and female gender (OR 3.7 95% CI 1.2–11.7) were associated with a higher probability of endoscopic improvement.
Conclusions
Anti-TNF therapy constitutes a good option for the treatment of established POR as it achieves endoscopic and clinical improvement in a great proportion of patients. Infliximab seems to be superior to adalimumab in reverting endoscopic lesions in the short-term.
A Spanish anthracite, with 5.6 wt % ash content, has been submitted to a two-stage activation process to explore its use as an activated carbon precursor. Several oxidation treatments, with two ...oxidizing agents (air and nitric acid), have been carried out to study the degree of coal oxidation and its influence on both the char porosity and the char activation. Two activating agents, CO2 and steam, have been used to prepare different burn-off samples to analyze the preoxidation effect on the porosity of the resulting activated carbons. The extent of the oxidation degree, followed by TPD experiment in He, increases with the severity of the oxidation treatment in the following order: air 4 h < air 8 h < 4 M HNO3 ≪ 15 M HNO3. All the oxidation treatments carried out in this study introduce important changes in the reactivity of the resulting chars and on the porous development. The more intense the preoxidation treatment is, and hence the amount of oxygen added to the anthracite, the higher is the porosity of the resulting chars. Activated carbons prepared from preoxidized chars, using CO2 or steam, present much larger porous development than the activated carbons coming from the original coal. The results show that the anthracite needs, prior to the pyrolysis process, an oxidation treatment to be used as an activated carbon precursor, as happens with caking coals. High surface area activated carbons (about 1300 m2/g at a 50% burn-off) can be obtained using nitric acid which has proved to be the most effective preoxidation agent. Comparison of both series of activated carbons, prepared in CO2 and steam, shows that steam develops the porosity of the resulting activated carbons more than CO2.
CaO dispersed on carbon as an SO2 sorbent MUNOZ-GUILLENA, M. J; MACIAS-PEREZ, M. C; LINARES-SOLANO, A ...
Fuel (Guildford),
05/1997, Letnik:
76, Številka:
6
Journal Article
High temperature SO2 retention by CaO MUNOZ-GUILLENA, M. J; LINARES-SOLANO, A; SALINAS-MARTINEZ DE LECEA, C
Applied surface science,
06/1996, Letnik:
99, Številka:
2
Journal Article
The kinetics of 1,3-dipolar cycloaddition involving azomethine ylides, generated from thermal 1,2-prototropy of the corresponding imino ester, employing differential scanning calorimetry (DSC), is ...surveyed. Glycine and phenylalanine derived imino esters have different behavior. The first one prefers reacting with itself at 75 °C, rather than with the dipolarophile. However, the α-substituted imino ester gives the cycloadduct at higher temperatures. Thermal dynamic analysis, by using ^sup 1^H NMR spectroscopy, of the neat reaction mixture of the glycine derivative reveals the presence of signals corresponding to the dipole in small abundance. The non-isothermal and isothermal DSC curves of the cycloaddition of phenylalaninate and diisobutyl fumarate are obtained from freshly prepared samples. The application of known kinetic models and mathematical multiple non-linear regressions (NLR) allow the determintion and comparison of E^sub a^, InA, reaction orders, and reaction enthalpy values. Finally a rate equation for each different temperature studied can be established for this particular thermal cycloaddition. PUBLICATION ABSTRACT
High temperature SO 2 retention by CaO Muñoz-Guillena, M.J; Linares-Solano, A; Salinas-Martínez de Lecea, C
Applied surface science,
1996, Letnik:
99, Številka:
2
Journal Article
Recenzirano
SO
2 retention with CaO at high temperature (1073 K), both in the absence and in the presence of O
2, has been studied. For this purpose, CaO samples coming from eight different limestones and ...commercial CaCO
3 have been used. Both limestone and CaO obtained from these samples were widely characterized. The ‘classical’ textural parameters of limestone or CaO (BET surface, pore volume, etc.) do not correlate with the SO
2 retention degree at 1073 K. However Temperature Programmed Reaction experiments (TPR) in a thermobalance may help to select the best limestone (CaO) to be used as SO
2 sorbent at 1073 K; in fact there seems to be a relation between the TPR type, the CaO dispersion (determined by CO
2 chemisorption at 573 K), and the retention degree reached. Consequently, CO
2 chemisorption at 573 K could be used to predict limestone behaviour with respect to SO
2 retention at 1073 K.
PDF
