Outcome in ulcerative colitis after switch from adalimumab/golimumab to infliximab: A multicenter retrospective study

Background

Anti-TNF therapies infliximab (IFX), adalimumab (ADA), and golimumab (GOL) are approved for treating moderate to severe ulcerative colitis (UC). In UC, only the switch from IFX to ADA has been investigated, reaching no more than 10–43% remission rates at 12 months.

Tacrolimus plus mycophenolate mofetil vs. cyclosporine plus everolimus in deceased donor kidney transplant recipients: three‐yr results of a single‐center prospective clinical trial

We compared in kidney transplantation two immunosuppressive regimens: tacrolimus plus mycophenolate mofetil (MMF) (TAC) and everolimus plus low‐dose cyclosporine (EVE). Sixty consecutive patients received TAC (30 patients) or EVE (30 patients) as immunosuppressive regimen; all subjects also received induction with basiliximab and corticosteroids. After three‐yr follow‐up, no difference was found in patient and graft survival (PTS: TAC: 97% vs. EVE: 100%; GS: TAC: 93% vs. EVE: 93%). The incidence of acute rejection was higher in the EVE group but the difference was not statistically significant (17% vs. 23%, p = ns). Patients in EVE showed higher serum cholesterol (205 ± 41 vs. 235 ± 41 mg/dL, p = 0.0012) and lower hemoglobin concentration (13.6 ± 1.4 vs. 12.4 ± 1.9, p = 0.01). Renal function was not significantly different in the two groups (3 Y creatinine: TAC 1.4 ± 0.8 vs. EVE 1.6 ± 0.8 mg/dL, p = ns). Treatment discontinuation was higher in the EVE group (TAC 17 vs. EVE 36%, p = ns). Our data show that in the middle‐term follow‐up, an immunosuppressive regimen with tacrolimus plus MMF has a similar efficacy and safety profile in comparison with the combination of low‐exposure cyclosporine plus everolimus. Further follow up could evidence the benefits related to the anti‐proliferative effects of everolimus.     

Short-Term Outcomes of Laparoscopy Combined with Enhanced Recovery Pathway after Ileocecal Resection for Crohn’s Disease: a Case-Matched Analysis

Background

Laparoscopy combined with an enhanced recovery pathway (ERP) is widely considered to be the first-choice option for patients with colorectal cancer. However, no previous reports have focused on patients with Crohn’s disease (CD) treated by laparoscopy and ERP.

Methods

Twenty patients with CD underwent laparoscopic ileocecal resection with an ERP at two institutions. The ERP protocol included no bowel preparation nor fasting, no nasogastric tube, no abdominal drains, early removal of urinary catheter, early solid dietary intake and mobilization, opioid-sparing analgesia and restrictive fluid management. This group was compared with a matched historical control group of 70 CD patients who underwent laparoscopic ileocecal resection treated with conventional care.

Results

Compliance with the ERP was high (≥80 %) for all items except no drain placement. A significantly earlier return of bowel function (time to first flatus and stool) was observed in the ERP group. Mean postoperative and total length of stay were significantly shorter in the ERP group. Postoperative complications were similar in both groups.

Conclusions

This is the first reported experience of laparoscopy with ERP in CD patients and suggests that optimized perioperative care combined with minimally invasive techniques may lead to further improvements in surgical outcomes for CD patients.     

Narrow-band imaging endoscopy to assess mucosal angiogenesis in inflammatory bowel disease: A pilot study

AIM: To investigate whether narrow band imaging (NBI) is a useful tool for the in vivo detection of angiogenesis in inflammatory bowel disease (IBD) patients. METHODS: Conventional and NBI colonoscopy was performed in 14 patients with colonic inflammation (8 ulcerative colitis and 6 Crohn’s disease). Biopsy samples were taken and CD31 expression was assayed immuno- histochemically; microvascular density was assessed by vessel count. RESULTS: In areas that were endoscopically normal but positive on NBI, ther...     

TNF-alpha suppresses the expression of clock genes by interfering with E-box-mediated transcription

Production of TNF-alpha and IL-1 in infectious and autoimmune diseases is associated with fever, fatigue, and sleep disturbances, which are collectively referred to as sickness behavior syndrome. In mice TNF-alpha and IL-1 increase nonrapid eye movement sleep. Because clock genes regulate the circadian rhythm and thereby locomotor activity and may alter sleep architecture we assessed the influence of TNF-alpha on the circadian timing system. TNF-alpha is shown here to suppress the expression of the PAR bZip clock-controlled genes Dbp, Tef, and Hlf and of the period genes Per1, Per2, and Per3 in fibroblasts in vitro and in vivo in the liver of mice infused with the cytokine. The effect of TNF-alpha on clock genes is shared by IL-1beta, but not by IFN-alpha, and IL-6. Furthermore, TNF-alpha interferes with the expression of Dbp in the suprachiasmatic nucleus and causes prolonged rest periods in the dark when mice show spontaneous locomotor activity. Using clock reporter genes TNF-alpha is found here to inhibit CLOCK-BMAL1-induced activation of E-box regulatory elements-dependent clock gene promoters. We suggest that the increase of TNF-alpha and IL-1beta, as seen in infectious and autoimmune diseases, impairs clock gene functions and causes fatigue.     

Acute severe colitis: infliximab and/or cyclosporine?

Acute severe ulcerative colitis is a serious condition that requires early hospitalization, with intensive monitoring and treatment. Despite the recent progress in the medical approach of Inflammatory Bowel Diseases acute severe ulcerative colitis remains a clinical challenge, with a mortality rate of nearly 1%. As of today, I.V. corticosteroids remain the 1(st)-line therapy for this complication. For non-responders (up to one-third of patients) possible options are surgery - whose timing is a critical point in the overall management of the disease - or rescue therapy with 2(nd)- line agents such as Cyclosporine and Infliximab. Here we will review the published studies dealing with the use of these medications in acute severe ulcerative colitis.     

Familial aggregation in inflammatory bowel disease：Is it genes or environment？

Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD path...     

Cortical excitability changes associated with fixation-off sensitivity: a case report

"Fixation-off sensitivity" (FOS) is an ideal human model for studying the features of epileptic discharges. Physiologically, FOS is expected to correspond to enhanced excitability of widespread cortical structures. To test this hypothesis, we measured by transcranial magnetic stimulation (TMS), the excitability level of the primary motor area in a 22-year-old woman with eyelid myoclonias and absences, who presented with generalized FOS. We also explored her visual system by pattern-reversal and flash-visual evoked potentials (VEPs). Both outside and within FOS, the cortical silent period was dramatically short, indicating defective γ-aminobutyric acid (GABA)(B) inhibition as a persistent background factor. The same was true for the short-interval intracortical inhibition, a TMS marker of cortical GABA(A) inhibition. The FOS state corresponded then to a pathologic enhancement of intracortical facilitation, a TMS marker of Glu/Asp transmission. During FOS, the flash VEP exhibited a hugely enhanced afterdischarge, expressing a pathologic overactivity of secondary visual areas. Within the limits of a single-case study, we thus provide electrophysiologic evidence supporting a grossly imbalanced cortical excitability, in both the frontal and posterior areas, as an important correlate of the present FOS subtype.     

Obsessive-compulsive-spectrum symptoms in patients with focal dystonia, hemifacial spasm, and healthy subjects

This study is aimed at investigating obsessive-compulsive disorder (OCD) in three groups of patients matched for age and gender; namely, focal dystonia (FD), hemifacial spasm (HFS), and healthy-control subjects (HC). All subjects were investigated with the Structured Clinical Interview for DSM-I, the Hospital Anxiety and Depression Scale, the Symptom Checklist-90, the Yale-Brown Obsessive-Compulsive Scale, and the Structured Clinical Interview for Obsessive-Compulsive Spectrum Self-Report, Lifetime Version (SCI-OBS-SR-LT). The prevalence of OCD was significantly higher in both FD and HFS than in HC participants. On the SCI-OBS, HFS patients showed higher scores than FD or HC for "contamination" and "aggressiveness." Despite the different pathophysiology, OCD is highly represented in both FD and HFS, with different thematic content characterizing the two conditions.