Adipose-derived stem cells and rabbit bone regeneration: histomorphometric, immunohistochemical and mechanical characterization

Background

In the last few years, several attempts have been made to treat large bone loss, including the use of tissue engineering with osteoinductive scaffolds and cells. This study highlights the role of mesenchymal stem cells from adipose tissue (ASCs; adipose-derived stem cells) in a rabbit bone regeneration model.

Methods

We compared the neoformed bone tissues achieved by treating critical tibial defects with either hydroxyapatite alone (HA, group I) or hydroxyapatite–autologous ASC constructs (ASCs-HA, group II), investigating their histomorphometric, immunohistochemical and biomechanical properties.

Results

After eight weeks of follow-up, we observed advanced maturation and a spatial distribution of new bone that was more homogeneous in the inner parts of the pores in group II, not just along the walls (as seen in group I). The new tissue expressed osteogenic markers, and biomechanical tests suggested that the newly formed bone in group II had a higher mineral content than that in group I. Although variability in differentiation was observed among the different cell populations in vitro, no differences in bone healing were observed in vivo; the variability seen in vitro was probably due to local microenvironment effects.

Conclusions

Tibial defects treated with rabbit ASCs-HA showed an improved healing process when compared to the process that occurred when only the scaffold was used. We suggest that implanted ASCs ameliorate the bone reparative process either directly or by recruiting resident progenitor cells.     

Reoperative Surgery After Repair of Postcholecystectomy Bile Duct Injuries: Is it Worthwhile?

Background

Repeat repair of bile duct injuries (BDIs) after cholecystectomy is technically challenging, and its success remains uncertain. We retrospectively evaluated the short- and long-term outcomes of patients requiring reoperative surgery for BDI at a major referral center for hepatobiliary surgery.

Methods

Between January 1991 and May 2011, we performed surgical BDI repairs in 46 patients. Among them, 22 patients had undergone a previous surgical repair elsewhere (group 1), and 24 patients had no previous repair (group 2). We compared the early and late outcomes in the two groups.

Results

The patients in group 1 were younger (48.6 vs. 54.8 years, p = 0.0001) and were referred after a longer interval (>1 month) from BDI (72.7 vs. 41.7 %, p = 0.042). Intraoperative diagnosis of BDI (59.1 vs. 12.5 %, p = 0.001), ongoing cholangitis (45.4 vs. 12.5 %; p = 0.02), and delay of repair after referral to our institution (116 ± 34 days vs. 23 ± 9 days; p = 0.001) were significantly more frequent in group 1 than in group 2. No significant differences were found for postoperative mortality, morbidity, or length of stay between the groups. Patients with associated vascular injuries had a higher postoperative morbidity rate (p = 0.01) and associated hepatectomy rate (p = 0.045). After a mean follow-up of 96.6 ± 9.7 months (range 5–237.2 months, median 96 months), the rate of recurrent cholangitis (6.5 %) was comparable in the two groups.

Conclusions

This study demonstrates that short- and long-term outcomes after surgical repair of BDI are comparable regardless of whether the patient requires reoperative surgery for a failed primary repair. Associated vascular injuries increase postoperative morbidity and the need for liver resection.     

Transplantation of Autologous Cultivated Conjunctival Epithelium for the Restoration of Defects in the Ocular Surface

Ocular surface disorders are often characterised by partial or complete loss of corneo-conjunctival epithelium, which causes dramatic functional and cosmetic problems. Depletion of stem cells and the scarcity of donor tissue available make large or bilateral defects challenging to reconstruct, and usually require the transplantation of heterotopic or allogeneic grafts. We investigated the feasibility of restoring severely damaged ocular surfaces with autologous cultivated conjunctival epithelium. Conjunctival cells were harvested from the healthy eyelid bed of four patients with oculopalpebral diseases. An epithelial sheet reproducing the original conjunctival epithelium was generated by serial cell culture. This was transplanted for the first time ever to our knowledge on to the ocular surface of the same patients. Take was excellent and the cultivated epithelium was stable, resulting in great improvement of patient's symptoms and cosmesis. Transplantation of cultivated conjunctival cells opens new perspectives in the treatment of severe ocular surface disorders.     

Occlus-o-Guide? versus Andresen activator appliance: neuromuscular evaluation

Background

The aim of the present study was to assess the muscular variations at the electromyography (EMG) level for the anterior temporalis muscles and masseter muscles during treatment with Occlus-o-Guide^® and Andresen activator appliances.

Methods

Eighty-two patients (35 males and 47 females) aged between 8 and 12 years (mean age, 10.5 ± 0.8 years) participated in the study. Fifty patients underwent treatment with an Occlus-o-Guide^® and 32 patients with an Andresen activator. All patients underwent EMG examination using a Freely EMG (De Gotzen, Legnano, Italy) and surface bipolar electrodes when the appliances were worn for the first time (T0), and after 6 months (T1) and after 12 months (T2) of appliance use.

Results

Statistical analysis showed that both at T0 and T2, the percent overlapping coefficient (POC) of the anterior temporalis muscles was not statistically different between the appliance groups. At T0, the POC of the masseter muscles was significantly lower for the Andresen appliance as compared to the Occlus-o-Guide^® (p = 0.02), while at T2 this significance was lost.

Conclusions

At insertion of an appliance, all patients show neuromuscular balance that does not correspond to orthognathic occlusion. Both appliances work by creating muscular imbalance. With the appliances in situ, EMG responses were generally analogous for the Occlus-o-Guide^® and the Andresen activator; however, the imbalance was greater and the recovery of the orthological muscular balance was slower in patients under treatment with the Andresen activator as compared to those with the Occlus-o-Guide^®.     

Foreign Accent Syndrome: In the ear of the beholder?

Background: The identification of accent type in patients with acquired accent change following brain damage (Foreign Accent Syndrome; FAS), may vary depending on the judge. Aims: This experiment tests the accent identification abilities of naive judges listening to speech samples from FAS patients versus healthy controls. Method & Procedures: A total of 52 naive judges listened to speech samples from speakers of British English, which were presented over audio CD. They were asked to identify the accent type, but were blind as to the identity of the participants vis-a-vis FAS versus control, and foreign versus native UK. Accuracy, variability, and confidence ratings were assessed as a function of participant and of accent type. Outcomes & Results: The naive judges displayed greater accuracy, consistency, and confidence in typing the control versus the FAS accents. There was a positive familiarity effect for the control, but not the FAS accents. Conclusions: The data provide preliminary support for the view that FAS is not exclusively “in the ear of the beholder”.     

Hypo-fractionated IMRT for patients with newly diagnosed glioblastoma multiforme: A 6 year single institutional experience

Objectives

Glioblastoma (GBM) is the most common malignant primary brain tumour in adults. Surgery and radiotherapy constitute the cornerstones for the therapeutic management of GBM. The standard treatment today is maximal surgical resection followed by concomitant chemo-radiation therapy followed by adjuvant TMZ according to Stupp protocol. Despite the progress in neurosurgery, radiotherapy and oncology, the prognosis still results poor.In order to reduce the long time of standard treatment, maintaining or improving the clinical results, in our institute we have investigated the effects of hypo-fractionated radiation therapy for patients with GBM.

Patients and methods

Sixty-seven patients affected by GBM who had previously undergone surgical resection (total, subtotal or biopsy) were enrolled between October 2005 and December 2011 in a single institutional study of hypo-fractionated intensity modulated radiation therapy (IMRT) followed or not by adjuvant chemotherapy with TMZ (6–12 cycles). The most important eligibility criteria were: biopsy-proven GBM, KPS ≥ 60, age ≥ 18 years, no previous brain irradiation, informed consensus. Hypo-fractionated IMRT was delivered to a total dose of 25 Gy in 5 fractions prescribed to 70% isodose. Response to treatment, OS, PFS, toxicity and patterns of recurrence were evaluated, and sex, age, type of surgery, Karnofsky performance status, Recursive Partitioning Analysis (RPA) classification, time between surgery and initiation of radiotherapy were evaluated as potential prognostic factors for survival.

Results

All patients have completed the treatment protocol. Median age was 64.5 years (range 41–82 years) with 31 females (46%) and 36 males (54%). Median KPS at time of treatment was 80. The surgery was gross total in 38 patients and subtotal in 14 patients; 15 patients underwent only biopsy.No grade 3–4 acute or late neurotoxicity was observed. With median follow-up of 14.9 months, the median OS and PFS were 13.4 and 7.9 months, respectively.

Conclusions

The hypo-fractionated radiation therapy can be used for patients with GBM, resulting in favourable overall survival, low rates of toxicity and satisfying QoL. Future investigations are needed to determine the optimal fractionation for GBM.     

Long-term outcome and need of re-operation in gastro-esophageal reflux surgery in children

Background

Fundoplication is considered a mainstay in the treatment of gastro-esophageal reflux. However, the literature reports significant recurrences and limited data on long-term outcome.

Aims

To evaluate our long-term outcomes of antireflux surgery in children and to assess the results of redo surgery.

Methods

We retrospectively analyzed all patients who underwent Nissen fundoplication in 8 consecutive years. Reiterative surgery was indicated only in case of symptoms and anatomical alterations. A follow-up study was carried out to analyzed outcome and patients’ Visick score assessed parents’ perspective.

Results

Overall 162 children were included for 179 procedures in total. Median age at first intervention was 43 months. Comorbidities were 119 (73 %), particularly neurological impairments (73 %). Redo surgery is equal to 14 % (25/179). Comorbidities were risk factors to Nissen failure (p = 0.04), especially children suffering neurological impairment with seizures (p = 0.034). Follow-up datasets were obtained for 111/162 = 69 % (median time: 51 months). Parents’ perspectives were excellent or good in 85 %.

Conclusions

A significant positive impact of redo Nissen intervention on the patient’s outcome was highlighted; antireflux surgery is useful and advantageous in children and their caregivers. Children with neurological impairment affected by seizures represent significant risk factors.

     

The 5-lipoxygenase enzymatic pathway in the mouse brain: young versus old

The 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism is an important source of inflammatory mediators, and is also present in the central nervous system. In this study, we assayed the expression levels and activity of 5-LO in different brain regions of young versus old C57Bl/6 mice. 5-LO mRNA was expressed in all the brain regions considered, i.e. cortex, hippocampus, and cerebellum. The highest expression level was observed in cerebellum compared with cortex and hippocampus, although it was not affected by aging. By contrast, 5-LO mRNA and protein levels were significantly increased in the hippocampus of old (25 months) versus young (3 months) mice. Finally, levels of the leukotriene B4, a metabolic product of 5-LO, were significantly increased in the hippocampus of old mice, but no difference was observed in cortex and cerebellum. These results demonstrate that the 5-LO enzymatic pathway is widely expressed in the mouse CNS, where significant changes are region-specific and age-dependent. This observation supports the hypothesis that 5-LO may be involved in diseases of the brain associated with aging.     

A novel t(2;3)(p11;q27) in a case of follicular lymphoma

Rearrangement of the BCL6 gene is found in follicular lymphomas and in diffuse large B cell lymphomas of follicular center cell origin. The breakpoints cluster mainly in a region spanning the first noncoding exon of the gene (the major breakpoint region). A second breakpoint cluster has also been identified upstream of the first BCL6 noncoding exon (the alternative breakpoint region [ABR]). To date, eight different rearrangements involving the ABR have been reported. Here, we describe a novel rearrangement involving a t(2;3)(p11;q27) translocation that affects the ABR in an unusual combination with the IGK locus.