Pulsatile Pump Decreases Risk of Delayed Graft Function in Kidneys Donated After Cardiac Death

Organ storage techniques have been under scrutiny to determine the best preservation method, particularly in donation after cardiac death (DCD) kidneys. Conflicting literature on the benefit of pulsatile perfusion (PP) over cold storage (CS) warrants further investigation. We analyzed the risk of developing delayed graft function (DGF) in recipients of DCD and donation after brain death (DBD) kidneys undergoing PP or CS. We stratified on basis of cold ischemic time (CIT) to determine the interaction of preservation techniques, CIT and DCD kidneys on developing DGF. Of 54 136 recipients, 4923 received DCD kidneys of which 3330 (67%) underwent PP. Of 49 213 DBD recipients, 7531 (15%) underwent PP. DCD had a higher risk of DGF versus DBD (adjusted odds ratio, AOR 3.2; 3.0–3.5). PP kidneys had less DGF (AOR 0.59; 0.56–0.63) compared to CS. Interaction models of method by donor type referenced to PP/DBD revealed CS/DBD kidneys had higher DGF (AOR 1.8; 1.7–1.9), whereas CS/DCD kidneys had the highest risk of DGF (AOR 5.01; 4.43–5.67). Even though suggestive for a benefit of PP on DGF, this retrospective analysis cannot address whether this is an intrinsic effect of PP or is associated with the logistics of PP such as discard of DCD kidneys based on pump parameters.     

Induction of Alloimmune Tolerance in Heart Transplantation Through Gene Silencing of TLR Adaptors

Toll‐like receptors (TLRs) activate biochemical pathways that evoke activation of innate immunity, which leads to dendritic cell (DC) maturation and initiation of adaptive immune responses that provoke allograft rejection. We aimed to prolong allograft survival by selectively inhibiting expression of the common adaptors of TLR signaling, namely MyD88 and TRIF, using siRNA. In vitro we demonstrated that blocking expression of MyD88 and TRIF led to reduced DC maturation. In vivo treatment of recipients with MyD88 and TRIF siRNA significantly prolonged allograft survival in the BALB/c > C57BL6 cardiac transplant model. Moreover, the combination of MyD88 and TRIF siRNA along with a low dose of rapamycin further extended the allograft survival (88.8 ± 7.1 days). Tissue histopathology demonstrated an overall reduction in lymphocyte interstitium infiltration, vascular obstruction and hemorrhage in mice treated with MyD88 and TRIF siRNA vector plus rapamycin. Furthermore, treatment was associated with an increase in the numbers of CD4⁺CD25⁺FoxP3⁺ regulatory T cells and Th2 deviation. To our knowledge, this study is the first demonstration of prolonging the survival of allogeneic heart grafts through gene silencing of TLR signaling adaptors, highlighting the therapeutic potential of siRNA in clinical transplantation.     

The invention of an iliosacral screw fixation guide and its preliminary clinical application

Objective: To introduce an iliosacral screw fixation guide and evaluate its efficacy in fixation of sacroiliac joint fracture‐dislocations. Methods: Between January 2011 and May 2011, eight patients (five men, three women) with sacroiliac joint fracture‐dislocation underwent percutaneous iliosacral screw fixation with the assistance of this minimally invasive guide and under CT guidance. The patients, aged from 26 to 56 years (mean 32 years), had vertically unstable pelvic fractures. Before surgery, six patients who had displacement of >2 cm in their sacroiliac joints underwent skeletal traction on the femoral condyle. The inserted sites were marked out on the affected side of their buttocks after the best screw trajectory had been determined under CT control. The gear that controls the direction of the minimally invasive guide was adjusted according to the inserting angle determined by CT scans. A K‐wire was inserted into the sacroiliac joint along the pilot sleeve of the guide, and a hollow screw (diameter 7.3 mm) was implanted into the sacroiliac joint along the K‐wire. Results: All eight operations were successful on the first attempt. The operations lasted from 10 to 20 minutes (mean 14 minutes). Immediate CT scans confirmed that all the screws had been placed in the desired positions, none had penetrated the bones and the configuration of the sacroiliac joints had been satisfactorily restored and firmly fixed. No patient experienced numbness or radiating pain in the lower limbs during surgery. There were no postoperative vascular or neurological complications. Conclusion: The minimally invasive guide can eliminate discrepancies resulting from the surgeon's own sensory input when inserting screws under the guidance of CT, making percutaneous iliosacral screw fixation more accurate, safe and simple.     

Clinical analysis of osteonecrosis of the femoral head induced by steroids

Objective: To explore the clinical characteristics of osteonecrosis of the femoral head (ONFH) induced by steroids. Methods: From January 2000 to October 2009, 497 hips in 270 cases of ONFH induced by steroids were studied. A questionnaire was administered when the patients were admitted; the questions concerned the underlying disease, duration of steroid usage, total dosage of steroid, incubation period (time interval between commencement of steroid therapy and onset of pain), severity of pain, location of initial complaint, primary diagnosis, time lag from onset of pain to final diagnosis and physical signs when admitted. The correlations between pain and Association Research Circulation Osseous (ARCO) stage, bone marrow edema (BME) and lesion size were analyzed. Results: The median of time between commencing steroid medication and developing ONFH for the 269 cases was 18 months (range, 2–384 months). 78.82% cases presented with pain within three years of steroid initiation, only 10.41% patients first complained of pain six or more years after commencing steroid therapy. Fifty‐six cases (20.82%) were misdiagnosed, lumbar disorders being the most frequent misdiagnoses. 79.29% of symptomatic hips presented with abnormal physical tests. Of 420 symptomatic hips, 166 hips were type C1, 223 hips type C2; 299 hips had collapsed; and there was BME in 209 hips. Conclusion: Most patients with ONFH induced by steroids complained of pain within 3 years of commencing steroid therapy. Pain was associated with lesion size, collapse and BME. Atypical location of pain, failure to perform a physical examination and MRI findings were the main causes of misdiagnoses.     

Evaluation of vertical traction radiography for predicting the outcome of moderate to severe rigid scoliosis correction

Objective: To determine the efficacy of imaging patients in a state of traction (“traction imaging”) for selection of upper and lower vertebrae to undergo instrumentation (UIV and LIV, respectively) to correct moderate to severe, rigid scoliosis. Methods: Twenty‐seven patients aged 11–21 years (average, 15.5 years) who had been treated at our institution for scoliosis of the thoracic spine between 2004 and 2008 were retrospectively analyzed. All patients were treated with the third multiple hook‐screw and rod instrumentation system. Standardized radiographic measurements (anteroposterior, sagittal, bending, fulcrum, traction) were taken and Cobb's angles, apical vertebra translation (AVT), and traction‐stable vertebrae determined. Results: All patients were followed for 6–36 months (average, 14.7 months). The Cobb's angles under preoperative vertical traction correlated positively with those measured postoperatively in standing anteroposterior film (P < 0.01). Preoperative AVT under vertical traction was significantly different from that measured postoperatively in standing anteroposterior film (P < 0.01). The traction radiography‐determined UIV slant angles were significantly different from those preoperatively without traction and the postoperative values, whereas traction radiography‐determined LIV values were not significantly different from those found preoperatively without traction (P > 0.05). Conclusions: Traction radiographic imaging is an effective, feasible preoperative assessment for determining which vertebrae are stable, designing the surgical strategy and choosing the UIV and LIV for correcting moderate to severe, rigid scoliosis.     

Identification of HLA‐DR4‐restricted immunogenic peptide derived from xenogenic porcine major histocompatibility complex class I molecule

Park C‐S, Kim K‐H, Im S‐A, Song S, Lee C‐K. Identification of HLA‐DR4‐restricted immunogenic peptide derived from xenogenic porcine major histocompatibility complex class I molecule. Xenotransplantation 2012; 19: 317–322. © 2012 John Wiley & Sons A/S. Abstract: Indirect recognition of xenoantigens has been implicated as the major mechanism underlying xenospecific CD4⁺ T‐cell activation in chronic rejection. We identified swine leukocyte antigen (SLA)‐derived immunogenic peptides that are presented in the context of human HLA‐DR4 molecules. The SLA class I‐derived peptides that bind HLA‐DRB1*0401, a representative of the DR4 supertype, were predicted using a computer‐assisted algorithm. The candidate peptides were synthesized, and their binding capacities to HLA‐DRB1*0401 were compared in a competitive ELISA using biotinylated hemagglutinin reporter peptides [HA_307‐319]. Peptide‐11 (LRSWTAADTAAQISK) was determined to exhibit the most potent binding capacity to HLA‐DRB1*0401 in vitro and thus selected for in vivo immunization. Immunization of HLA‐DRB1*0401‐transgenic mice with peptide‐11 elicited potent CD4⁺ Th1 responses. Peptide‐11 shares homology to α2 domains of three SLA‐1 alleles, six SLA‐2 alleles, and 14 SLA‐3 alleles. Thus, this study has important implications not only for the identification of an immunogenic indirect epitope shared by diverse SLA class I alleles, but also for the development of epitope‐specific immunoregulation strategies.     

Symptomatic chronic long head of biceps rupture: Surgical results

Purpose:

Chronic rupture of the long head of biceps (LHB) tendon is usually asymptomatic. However, some active patients suffer with long-term cramping pain associated with repetitive biceps use. The aim of this study is to review the outcomes of biceps tenodesis performed for chronic LHB ruptures.

Materials and Methods:

We performed a retrospective review of 11 consecutive patients who underwent biceps tenodesis for symptomatic chronic LHB ruptures over a 4-year period.

Results:

There were 10 men and one woman with an average age at surgery of 41 years (range 23-65). The mean follow-up was 29 months (range 6-60). In five cases a tendon was still identifiable and suitable for repair with an ‘in-bone’ interference screw. However, in six cases the tendon was not possible to tenodese with an interference screw. In these cases we used an ‘on-bone’ technique with suture anchors. All, except one, patients reported improvement in their arm pain (78%), strength (74%) and appearance. All, except one, were glad to have had the surgery.

Conclusions:

Symptomatic chronic LHB ruptures improve with a biceps tenodesis procedure. Due to the chronicity of the injury and possible degeneration of the tendon, a suitable tendon for ‘in-bone’ tenodesis may not be possible. In these cases an ‘on-bone’ footprint repair with suture anchors achieves good results.

Level of Evidence:

IV (retrospective case series).     

BMP‐2 mediates PGE2‐induced reduction of proliferation and osteogenic differentiation of human tendon stem cells

Tendon stem cells (TSCs) have been proposed to play a major role in the development of tendinopathy, which refers to pathological changes, such as calcification, in affected tendons. Using a human TSC (hTSC) culture model, this study investigated the effects of PGE₂, an inflammatory mediator present in injured tendons, on hTSC proliferation and differentiation as well as the molecular mediator for such PGE₂‐induced effects. We found that PGE₂ treatment of hTSCs decreased cell proliferation and caused osteogenic differentiation of hTSCs in a dose‐dependent manner. Also, PGE₂ treatment of hTSCs induced dose‐dependent BMP‐2 production in culture, and moreover, addition of BMP‐2 to hTSC culture decreased cell proliferation and induced hTSC differentiation into osteoblasts. Finally, addition of BMP‐2 antibodies to hTSC culture treated with PGE₂ nearly abolished PGE₂ effects on both cell proliferation and osteogenic differentiation. Taken together, the findings of this study showed that BMP‐2 mediates PGE₂‐induced reduction of proliferation and osteogenic differentiation of hTSCs. We suggest that such a mechanism may be partially responsible for the formation of calcified tissues in tendinopathic tendons seen in clinical settings. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:47–52, 2012