Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome

Irritable bowel syndrome(IBS)is a common clinical label for medically unexplained gastrointestinal symptoms,recently described as a disturbance of the microbiota-gut-brain axis.Despite decades of research,the pathophysiology of this highly heterogeneous disorder remains elusive.However,a dramatic change in the understanding of the underlying pathophysiological mechanisms surfaced when the importance of gut microbiota protruded the scientific picture.Are we getting any closer to understanding IBS’etiology,or are we drowning in unspecific,conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing?In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota,clinical microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation,neuroimaging and methods in microbiota analyses,and current and future challenges with big data analysis in IBS.     

Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn's disease

BACKGROUND: Episodic infliximab (IFX) treatment is associated with the formation of antibodies to IFX (ATIs) in the majority of patients, which can lead to infusion reactions and a shorter duration of response. Concomitant use of immunosuppressives (IS) reduces the risk of ATI formation. AIMS AND METHODS: To investigate which of the IS-that is, methotrexate (MTX) or azathioprine (AZA)-is most effective at reducing the risk of ATI formation, a multicentre cohort of 174 patients with Crohn's disease, treated with IFX in an on-demand schedule, was prospectively studied. Three groups were studied: no IS (n = 59), concomitant MTX (n = 50) and concomitant AZA (n = 65). ATI and IFX concentrations were measured in a blinded manner at Prometheus Laboratories before and 4 weeks after each infusion. RESULTS: ATIs were detected in 55% (96/174) of the patients. The concomitant use of IS therapy (AZA or MTX) was associated with a lower incidence of ATIs (53/115; 46%) compared with patients not taking concomitant IS therapy (43/59; 73%; p<0.001). The incidence of ATIs was not different for the MTX group (44%) compared with the AZA group (48%). Patients not taking IS therapy had lower IFX levels (median 2.42 microg/ml (interquartile range (IQR) 1-10.8), maximum 21 microg/ml) 4 weeks after any follow-up infusion than patients taking concomitant IS therapy (median 6.45 microg/ml (IQR 3-11.6), maximum 21 microg/ml; p = 0.065), but there was no difference between MTX or AZA. In patients who developed significant ATIs >8 microg/ml during follow-up, the IFX levels 4 weeks after the first infusion were retrospectively found to be significantly lower than in patients who did not develop ATIs on follow-up or had inconclusive ATIs. CONCLUSION: Concomitant IS therapy reduces ATI formation associated with IFX treatment and improves the pharmacokinetics of IFX. There is no difference between MTX and AZA in reducing these risks. ATI profoundly influences the pharmacokinetics of IFX. The formation of ATIs >8 microg/ml is associated with lower serum levels of IFX already at 4 weeks after its first administration.     

Raltitrexed plus cisplatin is cost-effective compared with pemetrexed plus cisplatin in patients with malignant pleural mesothelioma

Introduction

The National Institute for Health and Clinical Excellence (NICE) has previously recommended pemetrexed plus cisplatin for the treatment of patients with advanced malignant pleural mesothelioma (MPM) and WHO performance status 0-1. Subsequent to this appraisal, randomised controlled trial (RCT) data for raltitrexed plus cisplatin and comparing chemotherapy to active symptom control (ASC) has become available, allowing a more complete analysis of the comparative efficacy and cost-effectiveness of first-line chemotherapy in MPM.

Methods

An adjusted indirect comparison is used to estimate the relative efficacy of raltitrexed plus cisplatin and pemetrexed plus cisplatin. A cost-effectiveness model is used to assess the lifetime costs and health outcomes associated with these comparators and ASC. Patient level data from the EORTC 08983 trial are used to estimate baseline progression and survival rates. Relative treatment effects are taken from RCTs; cost and utility data from the literature.

Results

Raltitrexed plus cisplatin and pemetrexed plus cisplatin were not found to be statistically significantly different with respect to overall response, progression free survival or overall survival. The cost-effectiveness analysis found raltitrexed plus cisplatin to be cost-effective at a cost per quality adjusted life year of £13,454 compared to cisplatin and £27,360 compared to ASC. Pemetrexed plus cisplatin is dominated by raltitrexed plus cisplatin as the raltitrexed combination offers marginally higher quality adjusted life years (QALYs) and life years (LYs) at a substantially lower total cost.

Conclusion

Raltitrexed plus cisplatin is a cost-effective first-line treatment for MPM. This conclusion was maintained across a number of sensitivity analyses.     

Brown tumour of the spine in a renal transplant patient

We report a 30-year-old male who had undergone a renal transplant and suffered with secondary hyperparathyroidism. He presented with back pain and minimal neurological deterioration, caused by a thoracic brown tumour. The imaging findings, surgical treatment of the spinal lesion and outcome are discussed. We also discuss primary medical therapy and suggest a rational approach to further imaging of patients in whom brown tumour is suspected.     

What is the optimal medical treatment for stable cardiac surgical patients who go into atrial fibrillation after their operation?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was which medical strategy is the optimal treatment for stable patients going into atrial fibrillation post cardiac surgery. Altogether 281 papers were found from medline and 83 from the Cochrane Central Register of Controlled Trials using the reported search, of which 12 presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that there is very little evidence to support any one strategy over another.     

Glomangiomyoma (glomus tumor) of the kidney

We report herein a case of glomus tumor arising in the kidney of a 55-year-old woman, which was found incidentally on a computed tomographic scan. Partial nephrectomy revealed a 2-cm encapsulated mass that was architecturally similar to glomus tumor. Immunohistochemistry showed positivity of tumor cells for vimentin and smooth muscle actin. On electron microscopy, cytoplasmic thin filaments and dense bodies were seen, confirming the smooth muscle nature of the tumor. Glomus tumors arising in visceral organs are rare, and those arising in kidney are exceedingly rare.