Clinical, endoscopic and radiographic outcomes with ustekinumab in medically-refractory Crohn's disease: real world experience from a multicentre cohort.

BACKGROUND: Ustekinumab is a monoclonal antibody targeting interleukins-12 and -23, with efficacy in Crohn's disease (CD) demonstrated in clinical trials. AIM: To assess the real-world clinical, endoscopic and radiographic response and remission outcomes achieved with ustekinumab in medically-refractory CD. METHODS: A retrospective multicentre cohort study was performed on CD patients receiving ustekinumab between 2011 and 2016. The primary outcome was achievement of clinical and objective steroid-free response and remission at 3, 6 and 12 months. Clinical response and remission were defined by reduction in Harvey Bradshaw Index (HBI) of ≥3 points and an HBI ≤4 points respectively. Objective response was defined by improvement in endoscopic or radiographic CD, as assessed by ileocolonoscopy, contrast-enhanced ultrasound or CT/MR enterography. Objective remission was defined by endoscopic mucosal healing or complete resolution of inflammatory parameters on radiographic assessment. RESULTS: A total of 167 CD patients were treated with ustekinumab. 95.2% (159/167) previously failed anti-TNF therapy. Median follow-up was 45.6 weeks (IQR: 24.4-88.9). At 3 months, clinical response was achieved in 38.9% (65/167) and remission in 15.0% (25/167) of patients. At 6 months, clinical response was achieved in 60.3% (91/151) and remission in 25.2% (38/151) of patients. At 12 months, clinical response was achieved in 59.5% (66/111) and remission in 27.9% (31/111) of patients. Endoscopic or radiographic response was demonstrated in 54.5% (67/123) at 6 months and 55.8% (48/86) of patients at 12 months. CONCLUSIONS: Ustekinumab is an effective therapeutic option for inducing and maintaining clinical, endoscopic and radiographic response in patients with Crohn's disease failing anti-TNF therapy.

An in vitro study of the effect of mifepristone and ulipristal acetate on human sperm functions.

Ulipristal acetate (UPA) and mifepristone are currently well-established agents for emergency contraception. Both drugs are selective progestogen receptor modulators which have been shown to have better efficacy than the widely used levonorgestrel in prevention of pregnancy. However, there is only limited information on the action of UPA on sperm function. The present study compared the in vitro biological effects of mifepristone and UPA on human sperm functions. Spermatozoa from semen samples with normal semen parameters were isolated. Capacitated spermatozoa were pre-incubated with 0.04, 0.4, 4 and 40 µM mifepristone or UPA for 1 h. Sperm motility, viability, DNA integrity, capacitation, spontaneous acrosome reaction, spontaneous hyperactivation, zona pellucida (ZP) binding capability and intracellular calcium concentration ([Ca(2+)]i) were determined. The effects of mifepristone and UPA on progesterone-induced acrosome reaction, hyperactivation and [Ca(2+)]i were also studied. Our results showed that mifepristone and UPA dose-dependently suppressed progesterone-induced acrosome reaction, hyperactivation and [Ca(2+)]i at concentrations ≥0.4 µM in human spermatozoa. Both compounds did not affect sperm motility, viability, DNA integrity, capacitation, spontaneous acrosome reaction, spontaneous hyperactivation, ZP binding capability and [Ca(2+)]i. This study demonstrated that UPA and mifepristone modulate human sperm functions by acting as progesterone antagonists. The results enable us to gain a better understanding of the mechanisms by which mifepristone and UPA work for emergency contraception, and provide a scientific basis for their clinical application.

Review article: a decision-making algorithm for the management of pregnancy in the inflammatory bowel disease patient.

BACKGROUND: Inflammatory bowel disease affects patients who are in their reproductive years. There are many questions regarding the management of IBD patients who are considering or who are already pregnant. These include the effect of the disease and the medications on fertility and on the pregnancy outcome. AIM: To create an evidence-based decision-making algorithm to help guide physicians through the management of pregnancy in the IBD patient. METHODS: A literature review using phrases that include: 'inflammatory bowel disease', 'Crohn's disease', 'ulcerative colitis', 'pregnancy', 'fertility', 'breast feeding', 'delivery', 'surgery', 'immunomodulators', 'azathioprine', 'mercaptopurine', 'biologics', 'infliximab', 'adalimumab', 'certolizumab'. CONCLUSIONS: The four decision-making nodes in the algorithm for the management of pregnancy in the IBD patient, and the key points for each one are as follows: (i) preconception counselling - pregnancy outcome is better if patients remain in remission during pregnancy, (ii) contemplating pregnancy or is already pregnant - drugs used to treat IBD appear to be safe during pregnancy, with the exception of methotrexate and thalidomide, (iii) delivery and (iv) breast feeding - drugs used to treat IBD appear to be safe during lactation, except for ciclosporin. Another key point is that biological agents may be continued up to 30 weeks gestation. The management of pregnancy in the IBD patient should be multi-disciplinary involving the patient and her partner, the family physician, the gastroenterologist and the obstetrician.

Injury of the dorsal sensory branch of the ulnar nerve as a complication of arthroscopic repair of the triangular fibrocartilage.

This report presents a case of direct injury to the dorsal sensory branch of the ulnar nerve caused by arthroscopic repair of the triangular fibrocartilage complex. The dorsal sensory branch of the ulnar nerve was strangulated by one of the three pull-out sutures of the joint capsule, just ulnar to the extensor carpi ulnaris tendon. Pain and dysaesthesia of the ulnar side of the wrist was completely relieved after excision of the injured nerve segment. This complication can be avoided by careful exploration of the dorsal sensory branch of the ulnar nerve prior to suturing or passage of instruments during arthroscopy.