Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic. Results from the MIMIC Study (A Multi-centre cohort study evaluating the role of Inflammatory Markers in patients presenting with acute ureteric Colic)

Objectives There is conflicting data on the role of white blood cell count (WBC) and other inflammatory markers in spontaneous stone passage in patients with acute ureteric colic. The aim of the study was to assess the relationship of WBC and other routinely collected inflammatory and clinical markers including stone size, stone position and Medically Expulsive Therapy use (MET) with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic. Subjects and Methods Multi‐centre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across 4 countries (United Kingdom, Republic of Ireland, Australia and New Zealand). 4170 patients presented with acute ureteric colic and a computer tomography confirmed single ureteric stone. Our primary outcome measure was SSP as defined by the absence of need for intervention to assist stone passage. Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. Results 2518 patients were discharged with conservative management and had further follow up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, Neutrophils or CRP were seen to predict SSP, with an adjusted OR of 0.97 [95% CI 0.91 to 1.04, p = 0.38], 1.06 [95% CI 0.99 to 1.13, p = 0.1] and 1.00 [95% CI 0.99 to 1.00, p = 0.17], respectively. Medical expulsive therapy (MET) also did not predict SSP [adjusted OR 1.11 [95% CI 0.76 to 1.61]). However, stone size and stone position were significant predictors. SSP for stones 7mm. For stones in the upper ureter the SSP rate was 52% [95% CI 48 to 56], middle ureter was 70% [95% CI 64 to 76], and lower ureter was 83% [95% CI 81 to 85]. Conclusion In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management, neither WBC, Neutrophil count or CRP help determine the likelihood of spontaneous stone passage. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our findings represent the most comprehensive stone passage rates for each mm increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure

Comparison of the adjuvant activity of aluminum hydroxide and calcium phosphate on the antibody response towards Bothrops asper snake venom

The adjuvanticity of aluminum hydroxide and calcium phosphate on the antibody response in mice towards the venom of the snake Bothrops asper was studied. It was found that, in vitro, most of the venom proteins are similarly adsorbed by both mineral salts, with the exception of some basic phospholipases A2, which are better adsorbed by calcium phosphate. After injection, the adjuvants promoted a slow release of the venom, as judged by the lack of acute toxicity when lethal doses of venom were administered to mice. Leukocyte recruitment induced by the venom was enhanced when it was adsorbed on both mineral salts; however, venom adsorbed on calcium phosphate induced a higher antibody response towards all tested HPLC fractions of the venom. On the other hand, co-precipitation of venom with calcium phosphate was the best strategy for increasing: (1) the capacity of the salt to couple venom proteins in vitro; (2) the venom ability to induce leukocyte recruitment; (3) phagocytosis by macrophages; and (4) a host antibody response. These findings suggest that the chemical nature is not the only one determining factor of the adjuvant activity of mineral salts.International Foundation for Science/[B/5043-1]/IFS/SueciaUniversidad de Costa Rica/[741-B2-501]/UCR/Costa RicaFundação de Amparo à Pesquisa do Estado de São Paulo/[08/57898-0]/INCTTOX-CNPq/FAPESP/BrasilUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic: results from the Multi-centre cohort study evaluating the role of Inflammatory Markers In patients presenting with acute ureteric Colic (MIMIC) study

Objectives: To assess the relationship of white blood cell count (WBC) and other routinely collected inflammatory and clinical markers including stone size, stone position, and medical expulsive therapy use (MET), with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic, as there are conflicting data on the role of WBC and other inflammatory markers in SSP in patients with acute ureteric colic. Patients and methods: Multicentre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across four countries (UK, Republic of Ireland, Australia, and New Zealand). In all, 4170 patients presented with acute ureteric colic and a computed tomography confirmed single ureteric stone. Our primary outcome measure was SSP, as defined by the absence of need for intervention to assist stone passage (SP). Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. Results: In all, 2518 patients were discharged with conservative management and had further follow-up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, neutrophils count, nor C-reactive protein (CRP) predicted SSP, with an adjusted odds ratio (OR) of 0.97 (95% confidence interval [CI] 0.91–1.04, P = 0.38), 1.06 (95% CI 0.99–1.13, P = 0.1) and 1.00 (95% CI 0.99–1.00, P = 0.17), respectively. MET also did not predict SSP (adjusted OR 1.11, 95% CI 0.76–1.61). However, stone size and stone position were significant predictors. SSP for stones 7 mm. For stones in the upper ureter the SSP rate was 52% (95% CI 48–56), middle ureter was 70% (95% CI 64–76), and lower ureter was 83% (95% CI 81–85). Conclusion: In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management neither WBC, neutrophil count, nor CRP, helps determine the likelihood of SSP. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our present findings represent the most comprehensive SP rates for each millimetre increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention

Validation of a new optical diagnosis training module to improve dysplasia characterization in inflammatory bowel disease: a multicenter international study

Background and Aims: Inflammatory bowel disease (IBD) increases risk of dysplasia and colorectal cancer. Advanced endoscopic techniques allow for the detection and characterization of IBD dysplastic lesions, but specialized training is not widely available. We aimed to develop and validate an online training platform to improve the detection and characterization of colonic lesions in IBD: OPtical diagnosis Training to Improve dysplasia Characterization in Inflammatory Bowel Disease (OPTIC-IBD). Methods: We designed a web-based learning module that includes surveillance principles, optical diagnostic methods, approach to characterization, and classifications of colonic lesions using still images and videos. We invited gastroenterologists from Canada, Italy, and the United Kingdom with a wide range of experience. Participants reviewed 24 educational videos of IBD colonic lesions, predicted histology, and rated their confidence. The primary endpoint was to improve accuracy in detecting dysplastic lesions after training on the platform. Furthermore, participants were randomized 1:1 to get additional training or not, with a final assessment occurring after 60 days. Diagnostic performance for dysplasia and rater confidence were measured. Results: A total of 117 participants completed the study and were assessed for the primary endpoint. Diagnostic accuracy improved from 70.8% to 75.0% (P = .002) after training, with the greatest improvements seen in less experienced endoscopists. Improvements in both accuracy and confidence were sustained after 2 months of assessment, although the group randomized to receive additional training did not improve further. Similarly, participants’ confidence in characterizing lesions significantly improved between before and after the course (P < .001), and it was sustained after 2 months of assessment. Conclusions: The OPTIC-IBD training module demonstrated that an online platform could improve participants’ accuracy and confidence in the optical diagnosis of dysplasia in patients with IBD. The training platform can be widely available and improve endoscopic care for people with IBD. (Clinical trial registration number: NCT04924543.