Long-Term Efficacy and Safety of Cyclosporine in a Cohort of Steroid-Refractory Acute Severe Ulcerative Colitis Patients from the ENEIDA Registry (1989-2013): A Nationwide Multicenter Study.

OBJECTIVES: To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events. METHODS: Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators. RESULTS: Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P=0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P=0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P<0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed. CONCLUSIONS: Treatment with CyA showed a lower rate of SAE and a similar efficacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefit of sequential CyA-IFX for CyA non-responders is acceptable.

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Thermodynamic and Kinetic Fragility of Freon 113: The Most Fragile Plastic Crystal.

We present a dynamic and thermodynamic study of the orientational glass former Freon 113 (1,1,2-trichloro-1,2,2-trifluoroethane, CCl_{2}F-CClF_{2}) in order to analyze its kinetic and thermodynamic fragilities. Freon 113 displays internal molecular degrees of freedom that promote a complex energy landscape. Experimental specific heat and its microscopic origin, the vibrational density of states from inelastic neutron scattering, together with the orientational dynamics obtained by means of dielectric spectroscopy have revealed the highest fragility value, both thermodynamic and kinetic, found for this orientational glass former. The excess in both Debye-reduced specific heat and density of states (boson peak) evidences the existence of glassy low-energy excitations. We demonstrate that early proposed correlations between the boson peak and the Debye specific heat value are elusive as revealed by the clear counterexample of the studied case.

Glassy Anomalies in the Low-Temperature Thermal Properties of a Minimally Disordered Crystalline Solid.

The low-temperature thermal and transport properties of an unusual kind of crystal exhibiting minimal molecular positional and tilting disorder have been measured. The material, namely, low-dimensional, highly anisotropic pentachloronitrobenzene has a layered structure of rhombohedral parallel planes in which the molecules execute large-amplitude in-plane as well as concurrent out-of-plane librational motions. Our study reveals that low-temperature glassy anomalies can be found in a system with minimal disorder due to the freezing of (mostly in-plane) reorientational jumps of molecules between equivalent crystallographic positions with partial site occupation. Our findings will pave the way to a deeper understanding of the origin of the above-mentioned universal glassy properties at low temperature.

Effect of Chondroitin Sulphate on Pro-Inflammatory Mediators and Disease Activity in Patients with Inflammatory Bowel Disease.

BACKGROUND/AIMS: To evaluate the incidence rate of relapse in patients with inflammatory bowel disease (IBD) undergoing chondroitin sulphate (CS) treatment and its effect on the concentrations of several pro-inflammatory proteins. METHODS: Prospective, observational, 12-month follow-up study in patients with IBD in remission, starting CS (Condrosan®, Bioiberica S.A.) treatment for osteoarthritis (OA). Crohn's Disease Activity Index and modified Truelove-Witts severity index were calculated for Crohn's disease and ulcerative colitis (UC) respectively. Levels of vascular endothelial growth factor (VEGFA), -C, fibroblast growth factor 2, hepatocyte growth factor, angiopoietin (Ang)-1, Ang-2, transforming growth factor beta, tumour necrosis factor alpha, interleukin (IL)-1ß, IL-6, IL-12, IL-17, IL-23, intracellular adhesion molecule-1, vascular adhesion molecule-1, matrix metalloproteinase-3 and PGE2 were quantified by ELISA. OA joint pain was evaluated using a visual analogue scale. RESULTS: A total of 37 patients (19 UC and 18 Crohn's disease) were included. The mean values for OA joint pain decreased after 12 months from 5.9 ± 2.8 to 3.0 ± 2.3 (p < 0.05). Only 1 patient (with UC) flared during follow-up. The incidence rate of relapse was 3.4% per patient-year of follow-up. Mean serum VEGFA levels increased between baseline (492 pg/ml) and 12-month treatment (799 pg/ml; p < 0.05). CONCLUSION: The incidence of IBD relapse in patients under CS treatment was lower than that generally reported. This treatment might modulate VEGFA. CS decreases OA-related pain in patients with IBD.

Thermal properties of halogen-ethane glassy crystals: Effects of orientational disorder and the role of internal molecular degrees of freedom.

The thermal conductivity, specific heat, and specific volume of the orientational glass former 1,1,2-trichloro-1,2,2-trifluoroethane (CCl2F-CClF2, F-113) have been measured under equilibrium pressure within the low-temperature range, showing thermodynamic anomalies at ca. 120, 72, and 20 K. The results are discussed together with those pertaining to the structurally related 1,1,2,2-tetrachloro-1,2-difluoroethane (CCl2F-CCl2F, F-112), which also shows anomalies at 130, 90, and 60 K. The rich phase behavior of these compounds can be accounted for by the interplay between several of their degrees of freedom. The arrest of the degrees of freedom corresponding to the internal molecular rotation, responsible for the existence of two energetically distinct isomers, and the overall molecular orientation, source of the characteristic orientational disorder of plastic phases, can explain the anomalies at higher and intermediate temperatures, respectively. The soft-potential model has been used as the framework to describe the thermal properties at low temperatures. We show that the low-temperature anomaly of the compounds corresponds to a secondary relaxation, which can be associated with the appearance of Umklapp processes, i.e., anharmonic phonon-phonon scattering, that dominate thermal transport in that temperature range.

Third-line rescue therapy with bismuth-containing quadruple regimen after failure of two treatments (with clarithromycin and levofloxacin) for H. pylori infection.

BACKGROUND: Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin fails in >20 % of cases. A rescue therapy with PPI-amoxicillin-levofloxacin still fails in >20 % of patients. AIM: To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive eradication failures. METHODS: Prospective multicenter study of patients in whom 1st treatment with PPI-clarithromycin-amoxicillin and 2nd with PPI-amoxicillin-levofloxacin had failed. A 3rd eradication regimen with a 7- to 14-day PPI (standard dose b.i.d.), bismuth subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to 500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.). Eradication was confirmed by (13)C-urea-breath-test 4-8 weeks after therapy. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by means of a questionnaire. RESULTS: Two hundred patients (mean age 50 years, 55 % females, 20 % peptic ulcer/80 % uninvestigated-functional dyspepsia) were initially included, and two were lost to follow-up. In all, 97 % of patients complied with the protocol. Per-protocol and intention-to-treat eradication rates were 67 % (95 % CI 60-74 %) and 65 % (58-72 %). Adverse effects were reported in 22 % of patients, the most common being nausea (12 %), abdominal pain (11 %), metallic taste (8.5 %), and diarrhea (8 %), none of them severe. CONCLUSION: A bismuth-containing quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin- and levofloxacin-containing triple therapies.

[Consensus document on ultrasound training in Intensive Care Medicine. Care process, use of the technique and acquisition of professional skills]. / Documento de consenso para la formación en ecografía en Medicina Intensiva. Proceso asistencial, uso de la técnica y adquisición de competencias profesionales.

Ultrasound has become an essential tool in assisting critically ill patients. His knowledge, use and instruction requires a statement by scientific societies involved in its development and implementation. Our aim are to determine the use of the technique in intensive care medicine, clinical situations where its application is recommended, levels of knowledge, associated responsibility and learning process also implement the ultrasound technique as a common tool in all intensive care units, similar to the rest of european countries. The SEMICYUC's Working Group Cardiac Intensive Care and CPR establishes after literature review and scientific evidence, a consensus document which sets out the requirements for accreditation in ultrasound applied to the critically ill patient and how to acquire the necessary skills. Training and learning requires a structured process within the specialty. The SEMICYUC must agree to disclose this document, build relationships with other scientific societies and give legal cover through accreditation of the training units, training courses and different levels of training.

[Early statin therapy in acute myocardial infarction]. / Tratamiento precoz con estatinas en el infarto agudo de miocardio.

OBJECTIVES: To evaluate the effects of the early administration of statins during acute myocardial infarction (MI). DESIGN: A retrospective cohort study was carried out. SETTING: National (Spain). PATIENTS OR PARTICIPANTS: Patients included in the ARIAM registry from January 1999 to December 2008 with a diagnosis of MI. INTERVENTIONS: None. MAIN VARIABLES: We used logistic regression analysis and propensity scoring to determine whether the administration of statins during the first 24h of MI acts as a protective factor against: 1) mortality, 2) the incidence of lethal arrhythmias, or 3) cardiogenic shock. RESULTS: A total of 36 842 patients were included in the study. Statins were administered early in 50.2% of the patients. Statin administration was associated with younger patients with known previous dyslipidemia, obesity, a history of ischemic heart disease, heart failure, presence of sinus tachycardia, use of beta-blockers, angiotensin-converting enzyme inhibitors, thrombolysis and percutaneous coronary intervention. Mortality was 8.2% (13.2% without statin versus 3% with statin, P<.001). Multivariate analysis demonstrated that statin administration acted as a protective factor against mortality (adjusted OR 0.518, 95%CI 0.447 to 0.601). Continued use of statins was associated with a reduction in mortality (adjusted OR 0.597, 95%CI 0.449 to 0.798), and the start of treatment was a protective factor against mortality (adjusted OR 0.642, 95%CI 0.544 -0.757). Statin therapy also exerted a protective effect against the incidence of lethal arrhythmias and cardiogenic shock. CONCLUSIONS: These results suggest that early treatment with statins in patients with MI is associated with reduced mortality.

Anatomical and biomechanical factors of osteoporotic vertebral fracture and the occurrence of cascade fractures. / Factores anatómicos y biomecánicos de la fractura vertebral osteoporótica y la aparición de las fracturas en cascada.

Osteoporosis weakens the structural strength of bone to such an extent that normal daily activity may exceed the capacity of the vertebra to bear this load. Vertebral fracture and deformity is a hallmark of osteoporosis. The detriment of trabecular bone properties alone cannot explain the occurrence of osteoporotic vertebral fracture. The ability of the spine to bear and resist loads depends on the structural capacity of the vertebrae, but also on loading conditions arising from activities of daily living or low-energy trauma. This review describes the mechanical properties of the vertebral bone, the structural load-bearing capacity of the various elements forming the spine, the neuromuscular control of the trunk, as well as the biomechanics of the loads to which the spine is subjected in relation to the presence of osteoporosis and the risk of vertebral fracture. A better understanding of biomechanical factors may help to explain both the high incidence of osteoporotic vertebral fractures and their mechanism of production. Consideration of these issues may be important in the development of prevention and management strategies.

[Translated article] Anatomical and biomechanical factors of osteoporotic vertebral fracture and the occurrence of cascade fractures.

Osteoporosis weakens the structural strength of bone to such an extent that normal daily activity may exceed the capacity of the vertebra to bear this load. Vertebral fracture and deformity is a hallmark of osteoporosis. The detriment of trabecular bone properties alone cannot explain the occurrence of osteoporotic vertebral fracture. The ability of the spine to bear and resist loads depends on the structural capacity of the vertebrae, but also on loading conditions arising from activities of daily living or low-energy trauma. This review describes the mechanical properties of the vertebral bone, the structural load-bearing capacity of the various elements forming the spine, the neuromuscular control of the trunk, as well as the biomechanics of the loads to which the spine is subjected in relation to the presence of osteoporosis and the risk of vertebral fracture. A better understanding of biomechanical factors may help to explain both the high incidence of osteoporotic vertebral fractures and their mechanism of production. Consideration of these issues may be important in the development of prevention and management strategies.

Impact of COVID-19 disease on placental histopathology. PLAXAVID study.

BACKGROUND: The impact of COVID-19 on pregnancy has been analyzed suggesting an increased risk of placental lesions that might lead to maternal and neonatal complications. However, the current published evidence is not conclusive because contradictory results. METHODS: PLAXAVID is an observational, retrospective, histopathological, single-center study that aimed to evaluate the prevalence of vascular and inflammatory lesions in placental and umbilical cord samples of one hundred women infected by SARS-CoV-2 during pregnancy. RESULTS: The histopathological analysis showed that in most of the placentas (77.8%) there were signs of maternal vascular malperfusion (MVM; primary endpoint). The most common MVM features were an accelerated villous maturation (37.4%), central villous infarcts (33.3%), and villous agglutination (46.5%). Fetal vascular malperfusion (FVM) was identified in 57.6% of samples, and the most frequent features were hyalinized avascular villi (38.4%), fetal vascular thrombi (20.2%) and umbilical cord at risk of partial obstruction (14.1%). Acute and chronic inflammatory pathology were noticed in 22.2% and 49.5% of placentas, respectively. No significant correlations were found between MVM presence and the time, duration, and severity of infection, nor with the duration of pregnancy. However, in critically ill patients, the pregnancy duration (p=0.008), newborn weight (p=0.003), and APGAR test scores (p<0.001) were significantly lower. The same trend was observed considering the presence of infection at the time of delivery and in preterm births. CONCLUSION: A very high percentage of placentas with vascular and/or inflammatory lesions was found in the analyzed cohort. Therefore, PLAXAVID study results supported that COVID-19 should be considered a risk factor during gestation and requires close monitoring of pregnancy.

Management of Spinal Deformities Caused by Osteoporotic Vertebral Fractures. / Manejo de la deformidad espinal en el contexto de fracturas por compresión vertebral osteoporóticas.

Osteoporosis and fragility play a significant role in the treatment and planning of patients with deformity secondary to osteoporotic vertebral fracture (OVF). The resulting deformity can present significant challenges for its management, both from a medical and surgical perspective. The need for a specific classification for these deformities, including the potential for the development of artificial intelligence and machine learning in predictive analysis, is emerging as a key point in the coming years. Relevant aspects in preoperative optimization and management of these patients are addressed. A classification with therapeutic guidance for the management of spinal deformity secondary to OVF is developed, emphasizing the importance of personalized treatment. Flexibility and sagittal balance are considered key aspects. On the other hand, we recommend, especially with these fragile patients, management with minimally invasive techniques to promote rapid recovery and reduce the number of complications.

Safety of thiopurines and anti-TNF-α drugs during pregnancy in patients with inflammatory bowel disease.

OBJECTIVES: The safety of thiopurines and anti-tumor necrosis factor-α (TNF-α) drugs during pregnancy remains controversial, as the experience with these drugs in this situation is limited. Our aim is to assess the safety of thiopurines and anti-TNF-α drugs for the treatment of inflammatory bowel disease (IBD) during pregnancy. METHODS: Retrospective, multicenter study in IBD patients. Pregnancies were classified according to the therapeutic regimens during pregnancy or during the 3 months before the conception: non-exposed group, pregnancies exposed to thiopurines alone (group A), and pregnancies exposed to anti-TNF-α drugs (group B). An unfavorable Global Pregnancy Outcome (GPO) was considered if pregnancy developed with obstetric complications in the mother and in the newborn. RESULTS: A total of 187 pregnancies in the group A, 66 pregnancies in the group B, and 318 pregnancies in the non-exposed group were included. The rate of unfavorable GPO was different among the three groups (31.8% in non-exposed group, 21.9% in group A, and 34.8% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). The rate of pregnancy complications was similar among the three groups (27.7% in non-exposed, 20.9% in group A, and 30.3% in group B). The rate of neonatal complications was different among the three groups (23.3% in non-exposed group, 13.9% in group A, and 21.2% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). In the multivariate analysis, the treatment with thiopurines (odds ratio = 0.6; 95% confidence interval = 0.4-0.9, P = 0.02) was the only predictor of favorable GPO, whereas maternal age >35 years at conception was the only predictor of unfavorable GPO. The treatment with anti-TNF-α drugs was not associated with an unfavorable GPO. CONCLUSION: The treatment with thiopurines and anti-TNF-α drugs does not seem to increase the risk of complications during pregnancy and does seem to be safe for the newborn.

Health care costs of complex perianal fistula in Crohn's disease.

AIM: To evaluate the use of health care resources and the associated costs of complex perianal Crohn's disease (CD) from the National Health System perspective. METHODS: We conducted a multicenter, retrospective, observational study in which gastroenterologists from 11 hospitals in the Community of Madrid took part. Data was collected on the direct healthcare resources (pharmacological treatments, surgical procedures, laboratory/diagnostic tests, visits to specialists and emergency departments, and hospitalizations) consumed by 97 adult patients with complex perianal CD which was active at some point between January 1, 2005, and case history review. RESULTS: We recorded 527 treatments: 73.1% pharmacological (32.3% antibiotic, 20.5% immunomodulator, 20.3% biological) and 26.9% surgical. Mean annual global cost was €8,289/patient, 75.3% (€6,242) of which was accounted for by pharmacological treatments (€13.44 antibiotics; €1,136 immunomodulators; €5,093 biological agents), 12.4% (€1,027) by hospitalizations and surgery, 7.7% (€640) by medical visits, 4.2% (€350) by laboratory/diagnostic tests, and 0.4% (€30) by emergency department visits. CONCLUSIONS: Pharmacological therapies, and in particular biological agents, are the main cost driver in complex perianal CD; costs due to surgery and hospitalizations are much lower.

Element content of propolis collected from different areas of South Spain.

The aim of this work is to determine the content of essential and toxic elements in 25 raw propolis samples, when considering pollution agents and geographical and botanical factors. The microwave-assisted digestion was the most reliable and accurate method for determination of inorganic elements in propolis samples. The results were obtained using certified reference materials in a good agreement with certified values. Inductively coupled plasma atomic emission spectroscopy was used for the determination of 23 macro- and microelements (Ag, Al, As, B, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, P, Pb, S, Sb, Se, Si, Sn, and Zn). A Mercury analyzer was also utilized for the detection of the total Hg. Among the analyzed metals, Ca, K, Mg, Zn, Si, S, Fe, Al, P, and Na were found to be the most predominant. Heavy metals (As, Cd, Hg, and Pb) were determined in minimal concentration, and Pb was the highest mean contained toxic (<3.80 mg/kg), without influence on provisional tolerable weekly intake values. The method can be applied for routine analysis and quality and environmental pollution controls of toxic elements in propolis samples. The results obtained indicate no pollution of the collection areas and naturally high concentration of Al (460 ± 62.2 mg/kg).

Evaluation of liver fibrosis by transient elastography (Fibroscan®) in patients with inflammatory bowel disease treated with methotrexate: a multicentric trial.

BACKGROUND: Methotrexate is an effective treatment for inflammatory bowel disease (IBD). However, long-term treatments have been associated with the development of liver fibrosis. FibroScan® is a noninvasive, safe, and effective technique to evaluate liver fibrosis. AIM: To evaluate the presence of significant liver fibrosis by transient elastography (FibroScan®) in IBD patients treated with methotrexate. METHODS: Cross-sectional study including IBD patients treated with methotrexate from different hospitals. Clinical and analytical data, duration of treatment, and cumulative dose of methotrexate were obtained. Liver stiffness was assessed by FibroScan®. The cutoff value for significant liver fibrosis (according to METAVIR) was F ≥ 2: 7.1 kPa. Results. In the study, 46 patients were included, 30 women (65%), with a mean age of 43 ± 10 years. 31 patients had Crohn's disease (67.4%), 13 ulcerative colitis (28.3%), and 2 indeterminate colitis (4.3%). The mean cumulative dose of methotrexate was 1242 ± 1349 mg, with a mean treatment duration of 21 ± 24 months. The mean value of liver stiffness was 4.7 ± 6.9 kPa. There were 35 patients (76.1%) with F01, 8 patients (17.4%) with F = 2, and 3 patients with F ≥ 3 (6.5%). There were no differences in liver stiffness depending on sex, age, type of IBD, or cumulative dose of methotrexate. CONCLUSIONS: (1) Development of advanced liver fibrosis in IBD patients treated with methotrexate is exceptional. (2) There were no differences in liver stiffness depending on the type of IBD or the cumulative dose of methotrexate. (3) FibroScan® may be potentially useful for evaluation and follow-up of liver fibrosis in methotrexate-treated patients.

Differences in first neighbor orientation behind the anomalies in the low and high density trans-1,2-dichloroethene liquid.

Trans-1,2-dichloroethene (HClC=CClH) has several structural and dynamic anomalies between its low- and high-density liquid, previously found through neutron scattering experiments. To explain the microscopic origin of the differences found in those experiments, a series of molecular dynamics simulations were performed. The analysis of molecular short-range order shows that the number of molecules in the first neighbor shell is 12 for the high-density liquid and 11 for the low-density one. It also shows that the angular position of the center of mass of the first neighbor is roughly the same although the molecular orientation is not. In both liquids the first neighbor and its reference molecule arrange mainly in two configurations, each being the most probable in one of the liquids. First neighbors in the configuration that predominates in the high-density liquid tend to locate themselves closer to the reference molecule, an evidence that they are more strongly bonded. This arrangement facilitates a better packing of the rest of molecules in the first neighbor shell so that on average an additional molecule can be included, and is proposed to be the key in the explanation of all the observed anomalies in the characteristics of both liquids.

Numerically efficient real space theory of scattering from colloidal crystals.

The production of high-quality colloidal crystals demands precise quantitative characterization of their nanostructures. While small-angle radiation scattering is the technique of choice, a procedure for a comprehensive quantitative modeling of the data is still pending. A novel theory based on the pertinent radial pair distribution which takes into account orientational, positional, stacking disorder and grain effects is developed here. We also show how the scattering length density of the particles can be estimated from the positions of minima in the form factor. The obtained results can be cast as sums of analytical functions over the distribution function and, as such, are suitable for easy (automatic) parallelization. On the experimental side, we report on a strong extinction effect coming from grazing incidence specular reflection that we have been able to model analytically.

Effectiveness and Safety of the Switch from Remicade® to CT-P13 in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®. METHODS: Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The 'switch cohort' [SC] comprised patients who made the switch from Remicade® to CT-P13, and the 'non-switch' cohort [NC] patients remained under Remicade®. RESULTS: A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2-6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]. CONCLUSIONS: Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe.