Anti-LFA-1 improves pig islet xenograft function in diabetic mice when long-term acceptance is induced by CTLA4Ig/anti-CD40L

BACKGROUND: It has been previously demonstrated that addition of anti-LFA-1 to a combination of CTLA4Ig and anti-CD40L induces the permanent acceptance of dopaminergic fetal pig xenografts when transplanted into the brain of wild-type mice. The purpose of this study was to test whether this costimulation blockade also can induce acceptance of adult pig islets transplanted to C57BL/6 mice with streptozotocin-induced diabetes. METHODS: Recipients were treated with CTLA4Ig/anti-CD40L+/-anti-LFA-1 or isotype control antibodies during the first week after transplantation. Half of the costimulation blockade-treated recipients had their grafts removed after 8 weeks. The other half was observed up to 5 months. RESULTS: Recipients treated with CTLA4Ig/anti-CD40L/anti-LFA-1 had significantly lower blood glucose and gained more weight than CTLA4Ig/anti-CD40L-treated recipients. CTLA4Ig/anti-CD40L-treated recipients exhibited unstable blood glucose. IPGTT of these recipients revealed a slow recovery to normal blood glucose levels at week 4. In comparison, CTLA4Ig/anti-CD40L/anti-LFA-1 treated recipients exhibited a significantly superior glucose clearance. CTLA4Ig/anti-CD40L+/-anti-LFA-1 treated recipients did not produce anti-pig IgG, whereas control antibody-treated mice did. CD4+ T cells from costimulation blockade-treated recipients proliferated less than CD4+ T cells from control antibody-treated mice when co-cultured with syngeneic antigen presenting cells loaded with pig islet antigens. CONCLUSIONS: CTLA4Ig/anti-CD40L/anti-LFA-1-treated recipients had superior islet function compared with CTLA4Ig/anti-CD40L-treated recipients. However, both costimulation blockade regimens led to islet graft acceptance up to 5 months after a 1-week treatment.     

Fisherman's technique, introducing a novel method for using the umbilical port for removal of appendix during laparoscopic appendectomy

We describe a useful technique for removing the dissected appendix after laparoscopic appendectomy. This technique allows laparoscopic appendectomy to be completed with a single 10-mm and two 5-mm ports using only one 10-mm telescope. In this technique the dissected appendix is tied with an endoloop and then the end of this loop is railroaded through the umbilical port that will allow the appendix to be pulled (or fished) through the umbilical port. The advantage of this technique over older techniques is that it uses the full width of the 10 mm port, which makes it suitable for almost all cases with no chance of appendicular fragmentation during retrieval. The technique is safe, inexpensive, and does not need the use of retrieval bags.     

Outcome of rail fixator system in reconstructing bone gap

Background:

Bone loss following open fracture or infected gap nonunion is a difficult situation to manage. There are many modes of treatment such as bone grafting, vascularized bone grafting and bone transport by illizarov and monolateral fixator. We evaluated the outcome of rail fixator treatment in reconstructing bone and limb function. We felt that due to problems such as heavy apparatus, persistent pain, deformity of joints and discomfort caused by an Ilizarov ring fixator, rail fixator is a good alternative to treat bone gaps.

Materials and Methods:

20 patients (17 males and 3 females with mean age 30.5 years) who suffered bone loss due to open fracture and chronic osteomyelitis leading to infected gap nonunion. Ten patients suffered an open fracture (Gustilo type II and type III) and 10 patients suffered bone gap following excision of necrotic bone after infected nonunion. There were 19 cases of tibia and one case of humerus. All patients were treated with debridement and stabilization of fracture with a rail fixator. Further treatment involved reconstructing bone defect by corticotomy at an appropriate level and distraction by rail fixator.

Result:

We achieved union in all cases. The average bone gap reconstructed was 7.72 cm (range 3.5-15.5 cm) in 9 months (range 6-14 months). Normal range of motion in nearby joint was achieved in 80% cases. We had excellent to good limb function in 85% of cases as per the association for the study and application of the method of ilizarov scoring system[ASAMI] score.

Conclusion:

All patients well tolerated rail fixator with good functional results and gap reconstruction. Easy application of rail fixator and comfortable distraction procedure suggest rail fixator a good alternative for gap reconstruction of limbs.     

Treatment and Outcome of Patients with Skull Base Chordoma: A Meta-analysis

Objective Chordoma is a locally aggressive tumor. The aim of this study was to assess the efficacy of different surgical approaches and adjuvant radiation modalities used to treat these patients. Design Meta-analysis. Main Outcome Measures Overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). Results The 5-year OS and PFS rates of the whole cohort (n = 467) were 86% and 65.7%, respectively. The 5-year DSS for patients who underwent open surgery and endoscopic surgery was 45% and 49%, respectively (p = 0.8); PFS was 94% and 79%, respectively (p = 0.11). The 5-year OS of patients treated with surgery followed by adjuvant radiotherapy was 90% compared with 70% of those treated by surgery alone (p = 0.24). Patients undergoing partial resection without adjuvant radiotherapy had a 5-year OS of 41% and a DSS of 45%, significantly lower than in the total-resection group (p = 0.0002 and p = 0.01, respectively). The complication rates were similar in the open and endoscopic groups. Conclusions Patients undergoing total resection have the best outcome; adjuvant radiation therapy improves the survival of patients undergoing partial resection. In view of the advantages of minimally invasive techniques, endoscopic surgery appears an appropriate surgical approach for this disease.     

Effect of body mass index on the outcomes of patients with upper and lower urinary tract cancers treated by radical surgery: Results from a Canadian multicenter collaboration

ObjectiveTo evaluate the effect of body mass index (BMI) on the outcomes of patients with urinary tract carcinoma treated with radical surgery.Materials and methodsData were collected from 10 Canadian centers on patients who underwent radical cystectomy (RC) (1998–2008) or radical nephroureterectomy (RNU) (1990–2010). Various parameters among subsets of patients (BMI<25, 25≤BMI<30, and BMI≥30 kg/m²) were analyzed. Kaplan-Meier and multivariate analyses were performed to assess the effect of BMI on overall survival, disease-specific survival, and recurrence-free survival (RFS).ResultsAmong the 847 RC and 664 RNU patients, there was no difference in histology, stage, grade, and margin status among the 3 patient subsets undergoing either surgery. However, RC patients with lower BMIs (<25 kg/m²) were significantly older (P = 0.004), had more nodal metastasis (P = 0.03), and trended toward higher stage (P = 0.052). RNU patients with lower BMIs (<25 kg/m²) were significantly older (P = 0.0004) and fewer received adjuvant chemotherapy (P = 0.04) compared with those with BMI≥30 kg/m²; however, there was no difference in tumor location (P = 0.20), stage (P = 0.48), and management of distal ureter among the groups (P = 0.30). On multivariate analysis, BMI was not prognostic for overall survival, disease-specific survival, and RFS in the RC group. However, BMI≥30 kg/m² was associated with more bladder cancer recurrences and worse RFS in the RNU group (HR = 1.588; 95% CI: 1.148–2.196; P = 0.0052).ConclusionsIncreased BMI did not influence survival among RC patients. BMI≥30 kg/m² is associated with worse bladder cancer recurrences among RNU patients; whether this is related to difficulty in obtaining adequate bladder cuff in patients with obesity requires further evaluation.     

Biomechanical analysis of distal femoral fracture fixation: dynamic condylar screw versus locked compression plate

Background This human cadaveric study introduces a laboratory model to establish and compare the fixation stability of the distal femoral locking plate (DFLP) and dynamic condylar screw (DCS) in distal femoral fracture fixation.Materials and methods The study was conducted on 16 fresh cadaveric femoral specimens, 8 implanted with the DCS and the other 8 with the DFLP. The construct was made unstable by removing a standard-sized medial wedge with a 1-cm base (gap osteotomy) beginning 6 cm proximal to the lateral joint line in the distal metaphyseal region with loss of the medial buttress. Each specimen underwent axial and torsional stiffness testing along with cyclic axial loading to failure. The mean DEXA value for the DFLP group was 0.82 g/cm² and in the DCS group was 0.79 g/cm².Results Axial stiffness in the DFLP group was significantly higher than in the DCS group, but no significant difference was found in torsional stiffness between the groups. A significant difference was found in the load-to-failure results between the groups. Plastic and total deformation was significantly higher in constructs in the DCS group than in those in the DFLP group. Total energy absorbed before construct failure was also significantly higher in the DFLP group than in the DCS group.Conclusions The DFLP construct proved stronger than the DCS in both axial stiffness and cyclic loading, but similar in torsional stiffness in biomechanical testing in a simulated A3 distal femoral fracture.