Increased cortical neuronal responses to NMDA and improved attentional set-shifting performance in rats following prebiotic (B-GOS®) ingestion

We have previously shown that prebiotics (dietary fibres that augment the growth of indigenous beneficial gut bacteria) such as Bimuno^? galacto-oligosaccharides (B-GOS^®), increased N-methyl-D-aspartate (NMDA) receptor levels in the rat brain. The current investigation examined the functional correlates of these changes in B-GOS^®-fed rats by measuring cortical neuronal responses to NMDA using in vivo NMDA micro-iontophoresis electrophysiology, and performance in the attentional set-shifting task. Adult male rats were supplemented with B-GOS^® in the drinking water 3 weeks prior to in vivo iontophoresis or behavioural testing. Cortical neuronal responses to NMDA iontophoresis, were greater (+30%) in B-GOS^® administered rats compared to non-supplemented controls. The intake of B-GOS^® also partially hindered the reduction of NMDA responses by the glycine site antagonist, HA-966. In the attentional set-shifting task, B-GOS^® -fed rats shifted from an intra-dimensional to an extra-dimensional set in fewer trials than controls, thereby indicating greater cognitive flexibility. An initial exploration into the mechanisms revealed that rats ingesting B-GOS^® had increased levels of plasma acetate, and cortical GluN2B subunits and Acetyl Co-A Carboxylase mRNA. These changes were also observed in rats fed daily for 3 weeks with glyceryl triacetate, though unlike B-GOS^®, cortical histone deacetylase (HDAC1, HDAC2) mRNAs were also increased which suggested an additional epigenetic action of direct acetate supplementation. Our data demonstrate that a pro-cognitive effect of B-GOS^® intake in rats is associated with an increase in cortical NMDA receptor function, but the role of circulating acetate derived from gut bacterial fermentation of this prebiotic requires further investigation.     

Cost-effectiveness of vedolizumab compared with infliximab,adalimumab, and golimumab in patients with ulcerative colitis in the United Kingdom

Objective

To examine the clinical and economic impact of vedolizumab compared with infliximab, adalimumab, and golimumab in the treatment of moderately to severely active ulcerative colitis (UC) in the United Kingdom (UK).

Methods

A decision analytic model in Microsoft Excel was used to compare vedolizumab with other biologic treatments (infliximab, adalimumab, and golimumab) for the treatment of biologic-naïve patients with UC in the UK. Efficacy data were obtained from a network meta-analysis using placebo as the common comparator. Other inputs (e.g., unit costs, adverse-event disutilities, probability of surgery, mortality) were obtained from published literature. Costs were presented in 2012/2013 British pounds. Outcomes included quality-adjusted life-years (QALYs). Costs and outcomes were discounted by 3.5% per year. Incremental cost-effectiveness ratios were presented for vedolizumab compared with other biologics. Univariate and multivariate probabilistic sensitivity analyses were conducted to assess model robustness to parameter uncertainty.

Results

The model predicted that anti-tumour necrosis factor-naïve patients on vedolizumab would accrue more QALY than patients on other biologics. The incremental results suggest that vedolizumab is a cost-effective treatment compared with adalimumab (incremental cost-effectiveness ratio of £22,735/QALY) and dominant compared with infliximab and golimumab. Sensitivity analyses suggest that results are most sensitive to treatment response and transition probabilities. However, vedolizumab is cost-effective irrespective of variation in any of the input parameters.

Conclusions

Our model predicted that treatment with vedolizumab improves QALY, increases time in remission and response, and is a cost-effective treatment option compared with all other biologics for biologic-naïve patients with moderately to severely active UC.

     

Adolescents with inflammatory bowel disease feel ambivalent towards their parents' concern for them

This is a grounded theory study to identify concepts for describing how adolescents with inflammatory bowel disease (IBD) respond to their parents' concern for them. Ten adolescent boys and seven girls were interviewed. In the analysis four main categories emerged: ambivalence, ability/inability, compliance/resistance and trust/distrust. We found ambivalence to be the most distinctive theme to appear in the way in which these young people described how they felt about their parents' response to their disease. The core category ambivalence was expressed as an oscillation between seeking close contact with one's parents or, sometimes, staving them off, one moment feeling anxiously dependent upon them or turning to them for protection and support and the next, trying to achieve a dialogue with them. The core category comprised three subcategories, ability/inability, compliance/resistance and trust/distrust. The clinical support for young individuals with IBD should include an awareness of the simultaneous existence of conflicting attitudes, reactions and emotions.     

The third decade of HIV/AIDS: a brief epidemiologic update for dentistry

Dental professionals currently entering the dental workforce are witness to a significantly different set of oral health issues with HIV than those encountered when the epidemic began. Populations at risk for infection have changed over time and, in Canada, the United States, and the rest of the world, higher proportions of minorities and women have become infected. Medication regimens that help manage HIV as a more chronic disease have affected its presentation, its frequency and, perhaps, the significance of its oral manifestations. These medications may provoke comorbidities that challenge medical and dental disease management and health promotion. The dental office may become a site for rapid testing for HIV. The complexity of HIV infection and treatment behooves all health care professionals to be aware of developments in the prevention and epidemiology of HIV infection, and in oral health care for patients who are HIV-positive.     

Local treatment of rhabdomyosarcoma of the female genital tract: Expert consensus from the Children's Oncology Group,the European Soft-Tissue Sarcoma Group,and the Cooperative Weichteilsarkom Studiengruppe

The International Soft-Tissue Sarcoma Consortium (INSTRuCT) was founded as an international collaboration between different pediatric soft-tissue sarcoma cooperative groups (Children's Oncology Group, European Pediatric Soft-Tissue Sarcoma Group, and Cooperative Weichteilsarkom Studiengruppe). Besides other tasks, a major goal of INSTRuCT is to develop consensus expert opinions for best clinical treatment. This consensus paper for patients with rhabdomyosarcoma of the female genital tract (FGU-RMS) provides treatment recommendations for local treatment, long-term follow-up, and fertility preservation. Therefore, a review of the current literature was combined with recommendations of the treatment protocols of the appropriate clinical trials. Additionally, opinions of international FGU-RMS experts were incorporated into recommendations. Results were that the prognosis of FGU-RMS is favorable with an excellent response to chemotherapy. Initial complete surgical resection is not indicated, but diagnosis should be established properly. In patients with tumors localized at the vagina or cervix demonstrating incomplete response after induction chemotherapy, local radiotherapy (brachytherapy) should be carried out. In patients with persistent tumors at the corpus uteri, hysterectomy should be performed. Fertility preservation should be considered in all patients. In conclusion, for the first time, an international consensus for the treatment of FGU-RMS patients could be achieved, which will help to harmonize the treatment of these patients in different study groups.     

Association Between Ageing and Short-Term Survival Outcomes in Patients Undergoing Surgery for Primary Retroperitoneal Sarcoma

Annals of Surgical Oncology - As the population ages, more elderly patients are receiving surgery for retroperitoneal sarcoma (RPS). However, high-quality data investigating associations between...     

Morbidity of graft harvesting versus bone marrow aspiration in cell regenerative therapy

Purpose

Using bone marrow mesenchymal stem cells (MSCs) with aspiration from the iliac crest is commonly used in reconstructive orthopaedic surgery. Because bone marrow aspiration is a percutaneous technique, the morbidity as compared with the classical bone graft should be decreased.

Method

Therefore in a retrospective review of 523 consecutive cases of bone marrow aspiration performed at the Henri Mondor Hospital from 1990 to 2006 for the treatment of fractures, minor and major complications were identified and compared to the number of complications observed during the same period with 435 classical iliac crest bone graft procedures performed for the same indications of treatment of fractures. Minor complications included superficial infections, superficial seromas, and minor haematomas. Major complications included herniation of abdominal contents through massive bone graft donor sites, vascular injuries, deep infections at the donor site, neurologic injuries, deep haematoma formation requiring surgical intervention or transfusion, and iliac wing fractures.

Result

Bone marrow aspiration decreased significantly the number of complications as compared with harvesting classical iliac crest bone graft that was associated with significant morbidity. Adverse events were significantly lower (p?Conclusion In our series the number of complications with bone marrow aspiration was ten times less than the complications observed with the classical technique of bone piece harvesting from the iliac crest, and the complications were clearly less severe.     

Regenerative therapy with mesenchymal stem cells at the site of malignant primary bone tumour resection: what are the risks of early or late local recurrence?

Purpose

There is concern that regenerative cell-based therapies at the site of malignant primary bone tumours could result in increased risk of local tumour recurrence. We therefore investigated the long-term risks for site-specific recurrences in patients who had received an autologous bone marrow derived mesenchymal stem cell suspension to improve healing at the host-to-allograft bone junction of the reconstruction after bone tumour resection.

Methods

A total of 92 patients were treated from 1993 to 2003 with bone marrow-derived mesenchymal stem cells after bone tumour resection. Patients were monitored for cancer incidence from the date of first operation (1993) until death, or until 31 December 2013. The mean follow-up time was 15.4 years (range ten to 20 years). The average number of MSCs returned to the patient was 234,000 MSCs?±?215,000. The primary outcome was to evaluate the risk of tumorigenesis recurrence at the cell therapy treatment sites with radiographs and/or MRIs. The relative risk of cancer recurrence was expressed as the ratio of observed and expected number of cases according to three different control populations.

Results

Thirteen recurrences were found at the treatment sites among the 92 patients. The expected number of recurrences based on incidence in the three cohort populations was between 15 and 20 for the same cancer, age and sex distribution. The standardized incidence ratio (equal to observed cancers divided by expected cancers) for the entire follow-up period and for all recurrences was between 0.65 and 0.86 (95 % CI 0.60–1.20).

Conclusion

This study found no increased cancer local recurrence risk in patients after application of autologous cell-based therapy using bone marrow-derived mesenchymal stem cells at the treatment site after an average follow-up period of 15.4 years, ranging from ten to 20 years.     

Supercharging irradiated allografts with mesenchymal stem cells improves acetabular bone grafting in revision arthroplasty

Purpose

The procedure of bone allografting associated with a reinforcement device is widely used for acetabulum revision. However in absence of biologic fixation of the allograft, failure of the reconstruction may occur. We made the hypothesis that it would be possible to load these grafts with bone marrow derived mesenchymal stem cells (MSC) to rescue the osteogenic capacity of an allogenic dead bone and therefore enhance incorporation of allografts with the host bone and decrease the number of failures related to the allograft.

Method

We identified 60 patients who had undergone acetabular component revision for aseptic failure of cemented implants associated with massive periacetabular osteolysis and Paprosky type 3A or 3B classification (without pelvic discontinuity) between 1996 and 2001. The study group of 30 patients received MSCs in the allograft and at the host graft junction. The average total number of MSCs received by each patient was 195,000 cells (range 86,000–254,000 cells). The control group of 30 patients had no MSCs in the allograft. Patients were matched for the size of periacetabular osteolysis (Paprosky type 3A or 3B). We compared the evolution of the allografts and evaluated cup migration and revision of the hips as end points at a minimum of 12 years or until failure.

Result

Better radiographic graft union rates and less allograft resorption were observed with allografts loaded with stem cells. Allograft resorption was significantly decreased in the group with allograft loaded with MSCs (1.2 cm² —range 0–2.3 cm²—of resorption on radiographs in the group with MSCs; versus 6 cm², range 2.1–8.5 cm² in the group without MSCs). The rate of mechanical failure was highest (p?=?0.01) among the 30 patients with allograft without stem cells (9/30; 30 %) compared with no failures for patients with allograft loaded with stem cells. Revision of the cup was necessary in nine patients in the control group. No revision was performed in the 30 patients of the study group with MSCs.

Conclusion

For acetabular defect reconstruction, loading the allograft with MSCs has resulted in a lower rate of failure as compared with allograft without MSCs.