Implications of the Collar Sign in Incompletely Occluded Aneurysms after Pipeline Embolization Device Implantation: A Follow-Up Study.

BACKGROUND AND PURPOSE: The angiographic collar sign has been recently described in patients with incompletely occluded aneurysms after Pipeline Embolization Device implantation. The long-term implications of this sign are unknown. We report angiographic outcomes of patients with the collar sign with follow-up of up to 45 months and the implications of this angiographic finding. MATERIALS AND METHODS: We performed a retrospective review of a prospectively maintained data base of patients who underwent Pipeline Embolization Device implantation for an intracranial aneurysm at our institution between January 2014 and December 2016. We included patients with a collar sign at the initial follow-up angiogram after Pipeline Embolization Device implantation. RESULTS: A total of 198 patients with 285 aneurysms were screened for the collar sign on initial and subsequent follow-up angiograms. There were 226 aneurysms (79.3%) with complete occlusion at the first follow-up. Of 59 incompletely occluded aneurysms, 19 (32.2%) aneurysms in 17 patients were found to have a collar sign on the first angiographic follow-up (median, 6 months; range, 4.2-7.2). Ten (52.6%) aneurysms underwent retreatment with a second Pipeline Embolization Device, which resulted in aneurysm occlusion in 1 (10%) patient. There were only 3 (15.8%) aneurysms with complete occlusion at the last follow-up, 2 (10.5%) of which had a single Pipeline Embolization Device implantation and another single (5.3%) aneurysm with a second Pipeline Embolization Device implantation. CONCLUSIONS: A collar sign on the initial angiogram after Pipeline Embolization Device placement is a predictor of poor aneurysm occlusion. Because the occlusion rates remain equally low regardless of retreatment in patients with a collar sign, radiologic follow-up may be more appropriate than retreatment.

Cortical stroke affects activity and stability of theta/delta states in remote hippocampal regions.

Cognitive impairment is a common outcome of ischemic stroke. Our previous work has shown that an experimental stroke in the cortex reduces activity in remote hippocampal layers in rats. This study seeks to uncover the underlying functional connections between these areas by analyzing changes to oscillatory activity, signal power, and communication. We induced an ischemic stroke in the left somatosensory cortex of rats and used linear micro-electrode arrays to simultaneously record from cortex and hippocampus under urethane anesthesia at two weeks and one month after stroke. We found significant increase in signal power, as well as an increase in the number of brain state changes in response to stroke. Our results suggest that the cortex modulates the activity and stability of hippocampal oscillations, which is disrupted following cortical stroke that can lead to cognitive impairment.

Should sagittal osteotomy line be parallel to tibial posterior slope in high tibial osteotomy?

BACKGROUND: The reason why the osteotomy line in the sagittal view should be parallel to the medial tibial posterior slope in open wedge high tibial osteotomy (OWHTO) remains unclear. In addition, previous study reported that a posterolateral hinge position led to an increase in tibial posterior slope (TPS) after OWHTO. Our aims were to examine the relationships between angles among the tibial plateau and osteotomy planes or the hinge point and the change in TPS, and the location of the hinge position after OWHTO using three-dimensional computed tomography (3DCT). We hypothesized that the sagittal angle between the tibial plateau and osteotomy planes with an anterior-widening proximal tibial fragment resulted in increased TPS, and the hinge position located posterolaterally. METHODS: Preoperative planning anticipated a weight-bearing line ratio of 62% on the radiograph. The anterior gap was 67% of the posterior gap in OWHTO. We identified the tibial plateau and upper and lower osteotomy planes on 3DCT of 82 patients with symptomatic medial osteoarthritic knee after OWHTO. The osteotomy plane angles between the tibial plateau and upper osteotomy planes, and opening gap angles between both osteotomy planes in the coronal and sagittal views were measured. The anteroposterior (AP) and lateral hinge position was displayed as a percentage on the upper osteotomy plane. We assessed the relationships among them. RESULTS: The TPS significantly increased after OWHTO (p = 0.002). There was no significant difference between the sagittal osteotomy plane angle and the change in TPS. The sagittal opening gap angle and the AP hinge position ratio were significantly correlated with the change in the TPS (r = 0.477 p < 0.001 and r = - 0.342, p = 0.002, respectively). The hinge position was located a mean of 16.0% from the lateral and 48.6% from the posterior tibial edge in the upper osteotomy plane. CONCLUSIONS: Contrary to our expectation, the osteotomy plane did not need to be parallel to the tibial plateau plane in the sagittal view. However, the osteotomy gap should be rectangular in the sagittal view. The hinge position located nearly in the center of the sagittal view.

Edoxaban is effective in reducing the incidence of asymptomatic phlebographic events following closed-wedge high tibial osteotomy.

INTRODUCTION: The purpose of this study was twofold: to investigate whether edoxaban significantly decreases the rate of venous thromboembolism (VTE) following closed-wedge high tibial osteotomy (CWHTO), in terms of phlebographic event, and to determine whether edoxaban is safe or increases the rate of hemorrhagic complications. We hypothesized that edoxaban would decrease the incidence of VTE and would not increase the rate of hemorrhagic complications. MATERIALS AND METHODS: We randomly enrolled 60 patients undergoing CWHTO. The patients were divided into two groups: one group receiving edoxaban (15mg in 5 patients, 30mg in 23 patients) and a non-edoxaban group. All patients underwent computed tomography venography on day 7to diagnose postoperative VTE. Blood samples were obtained on the day before CWHTO and on postoperative days 1, 3, 7 and 14. The incidence of VTE and hemorrhagic events in both groups was compared using unpaired Student t-test or chi-square test. RESULTS: The incidence of VTE was significantly greater in the non-edoxaban group (31.3% versus 7.1%; P=0.02). The incidence of deep vein thrombosis (DVT) was also significantly greater in the non-edoxaban group (28.1% versus 3.6%; P=0.01). A single patient from the edoxaban group experienced major bleeding. On days 3 and 7, D-dimer levels were significantly lower in the edoxaban group (P=0.03 and 0.003, respectively). On days 3, 7 and 14, activated partial thromboplastin time was significantly greater in the edoxaban group (P=0.02, 0.01 and 0.006, respectively). CONCLUSION: Patients undergoing CWHTO are at risk of postoperative VTE. Edoxaban helps prevent asymptomatic phlebographic VTE and DVT following CWHTO; however, the risk of major bleeding must be considered. LEVEL OF EVIDENCE: II.

Influence of coronal bowing on the lower alignment and the positioning of component in navigation and conventional total knee arthroplasty.

BACKGROUND: Coronal alignment is an important factor for the function and longevity of total knee arthroplasty (TKA). Coronal bowing of the lower extremity is common among Asians and it may pose a risk for malalignment of the lower leg and malposition of component. HYPOTHESIS: We hypothesized that coronal bowing itself has a risk for malalignment of the lower leg and malposition of femoral/tibial components and that navigation TKA is beneficial for patients with coronal bowing. We investigated the incidence of femoral/tibial bowing in patients treated with TKA and compared the radiographic parameters between the navigation group and the conventional group. Additionally, the influence of coronal bowing on these radiographic parameters was investigated. MATERIALS AND METHODS: We enrolled 35 patients with knee osteoarthritis and 70 bilateral simultaneous TKAs. The patients underwent TKA with the use of a computer tomography-free navigation in one knee and conventional TKA in the contralateral knee. Preoperative coronal bowing were measured, and the subjects were divided into 2 subgroups, i.e. the bowing group and the non-bowing group. Lateral bowing was expressed as plus (+) and medial bowing was expressed as minus (-). Various radiographic parameters, including coronal bowing, lower leg alignment, component position, and outliers were compared between the navigation group and the conventional group. RESULTS: Femoral bowing varied from -7.4° to 10.9° with an average of 3.0°. Tibial bowing varied from -4.1° to 4.6° with an average of 0.4°. The femoral component was placed more properly in the navigation group. Number of outlier regarding to the coronal femoral component angle to the femoral mechanical axis was 14 cases (37.8%) in the bowing group and 6 cases (18.2%) in the non-bowing group (P=0.04). DISCUSSION: In conclusion, coronal femoral bowing has an important effect on femoral bone cut in TKA. The navigated TKA was more consistent than conventional TKA in aiding proper alignments of femoral component. LEVEL OF EVIDENCE: Level II, comparative prospective study.

Predictive factors for the progression of spontaneous osteonecrosis of the knee.

PURPOSE: To assess potentially predictive factors that were evaluated 1 year after the onset of symptoms in patients with spontaneous osteonecrosis of the knee (SONK) and to determine receiver operating characteristic (ROC) curve cut-off values. METHODS: Within 1 year of symptom onset, patients with SONK-selected treatment options, mainly based on severity of pain, chose either conservative treatment (n = 27 knees) or operative treatment (n = 27 knees). Knee and whole-leg radiographs, knee MRIs and bone mineral density scans of the lumbar spine, femoral neck and femoral condyles were obtained. The parameters measured were: (1) anatomical angle on whole-leg radiograph and (2) lesion size and medial meniscus extrusion on MRI. RESULTS: The anatomical angle and lesion size in the sagittal section (depth) on MRI were markedly larger in the operative treatment group than those in the conservative treatment group. The anatomical angle and depth on MRI of SONK at Stages 1-3 were significantly different between groups, with odds ratios (95 % confidence intervals) of 1.16 (1.18-2.34) and 1.11 (1.01-1.23). One year after symptom onset, ROC curve cut-off value for anatomical angle was 180° and depth on MRI was 20 mm. CONCLUSION: An anatomical angle >180° and depth >20 mm on MRI were predictive factors for a poorer prognosis 1 year after symptom onset in patients with SONK. Our results on radiographs and MRI provided a predictive prognosis for patients with SONK at the initial visit to their orthopaedic surgeons. LEVEL OF EVIDENCE: III.

Usefulness of long tibial axis to measure medial tibial slope for opening wedge high tibial osteotomy.

PURPOSE: To assess which tibial slope measurements on knee, whole leg radiographs and three-dimensional reconstructed computed tomography (CT) were useful in clinical practice before and after opening wedge high tibial osteotomy. METHODS: Medial and lateral tibial slopes on knee, whole leg radiographs and three-dimensional reconstructed CT were measured in 50 patients with knee osteoarthritis. To investigate the intraobserver reproducibility and interobserver reliability for each medial and lateral tibial slope on knee, whole leg radiographs and CT, the measurements were repeated twice by two observers. The statistical differences between the medial and lateral tibial slopes obtained by the three methods, and the differences and correlation coefficients for the medial and lateral tibial slopes between knee or whole leg radiographs and CT were calculated. RESULTS: The reproducibility and reliability of medial and lateral tibial slopes on CT were superior to those on whole leg or knee radiographs. The medial and lateral tibial slopes on whole leg radiographs had better reproducibility and reliability than those on knee radiographs. The mean medial tibial slopes on knee, whole leg radiographs and CT were 9.3 ± 3.4°, 12.3 ± 4.3° and 11.0 ± 3.9°, respectively. The mean lateral tibial slopes were 7.9 ± 3.1°, 9.6 ± 3.6° and 9.3 ± 2.9°, respectively. The medial tibial slopes on knee, whole leg radiographs and CT were significantly higher than the lateral tibial slopes (p < 0.01 for all). CONCLUSIONS: Tibial slope measurements using CT required time and specialized software. Therefore, measurements of the medial tibial slope using the long tibial axis on whole leg radiographs were more reproducible and reliable and could be an alternative to CT in clinical practice. LEVEL OF EVIDENCE: III.

Impairment of host resistance to helminthes with age in murine small intestine.

Age-associated alterations of Th2 immune responses against nematode parasites are largely unknown. We investigated primary and memory responses against two types of gastrointestinal nematode parasites, Heligmosomoides polygyrus (Hp) and Nippostrongylus brasiliensis (Nb), in aged mice. The small intestinal gene expression of Th2 cytokines was almost unchanged after primary (Nb and Hp) and secondary infection (Hp) in aged mice in contrast to strongly increased small intestinal gene expression of Th2 cytokines in young (3-month-old) mice. Mucus production decreased (Nb), and worm expulsion was impaired (Nb and Hp) compared with the young mice. Immunofluorescent staining revealed that after Hp infection, the number of alternatively activated macrophages, which are induced by Th2 cytokines, was lower in the aged mice. On the other hand, the number of CD4(+) T cells recruited to the worm cysts was normal compared with the young mice. These results suggest that migration of CD4(+) T cells to the host-parasite interface is not affected by ageing. Alterations in Th2 immune responses in aged mice might be due to inappropriate or insufficient activation of CD4(+) T cells in the submucosa.

Reproducibility of condylar twist angle measurement using computed tomography and axial radiography of the distal femur.

INTRODUCTION: It is essential to understand rotational alignment of the distal femur when performing total knee arthroplasty (TKA). Several rotational landmarks including condylar twist angle (CTA) are used for preoperative planning and during TKA. Axial radiography of the distal femur is used for measuring the CTA, and assessing rotational alignment in TKA. The aim of this study was to investigate the reliability and the reproducibility of the CTA using two different methods and evaluate if CTA differed between varus and valgus knees and between normal and osteoarthritic knees. MATERIALS AND METHODS: CTA were obtained from 144 knees (77 patients) having total knee or hip arthroplasty using computed tomography (CT) and axial radiography. Subjects were divided into five groups based on femorotibial angle (FTA) and into four groups based on the severity of knee osteoarthritis. The intra-observer and inter-observer reliabilities of these methods and inter-method differences were evaluated. RESULTS: The mean CTA was 7.02° with axial radiography, and 6.87° with CT images. There were no significant differences among the five FTA groups and among the four osteoarthritis groups. In total, intra-/inter-observer, and inter-method intraclass correlation coefficients were substantial or almost perfect in the scoring system of Landis et al. However, discrepancies ≥ 2° between the two methods were observed in more than 20% of knees. CONCLUSION: The CTA should be reassessed by more than two observers or two methods for precise preoperative TKA planning in cases where it is difficult to identify the bony landmarks for CTA measurements. LEVEL OF EVIDENCE: Level III.

Five- to ten-year outcome following medial opening-wedge high tibial osteotomy with rigid plate fixation in combination with an artificial bone substitute.

Between 2003 and 2007, 99 knees in 77 patients underwent opening wedge high tibial osteotomy. We evaluated the effect of initial stable fixation combined with an artificial bone substitute on the mid- to long-term outcome after medial opening-wedge high tibial osteotomy (HTO) for medial compartmental osteoarthritis or spontaneous osteonecrosis of the knee in 78 knees in 64 patients available for review at a minimum of five years (mean age 68 years; 49 to 82). The mean follow-up was 6.5 years (5 to 10). The mean Knee Society knee score and function score improved from 49.6 (SD 11.4, 26 to 72) and 56.6 (SD 15.6, 5 to 100) before surgery to 88.1 (SD 12.5, 14 to 100) and 89.4 (SD 15.6, 5 to 100) at final follow-up (p < 0.001) respectively. There were no significant differences between patients aged ≥ 70 and < 70 years. The mean standing femorotibial angle was corrected significantly from 181.7° (SD 2.7°, 175° to 185°) pre-operatively to 169.7° (SD 2.4°, 164° to 175°) at one year's follow-up (p < 0.001) and 169.6° (SD 3.0°, 157° to 179°) at the final follow-up (p = 0.69 vs one year). Opening-wedge HTO using a stable plate fixation system combined with a bone substitute is a reliable procedure that provides excellent results. Although this treatment might seem challenging for older patients, our results strongly suggest that the results are equally good.

The extent of degeneration of cruciate ligament is associated with chondrogenic differentiation in patients with osteoarthritis of the knee.

OBJECTIVE: Degeneration in cruciate ligaments results from abnormal biomechanical stress and the aging process. Such degeneration is a common outcome in patients with osteoarthritis (OA) of the knee and contributes to the progression of OA. However, to date, there are no specific markers that can predict the extent of ligament degeneration. We hypothesized that the extent of degeneration has correlations to increased chondrogenic potential. METHODS: Twenty anterior cruciate ligaments (ACLs) and 30 posterior cruciate ligaments (PCLs) from 30 knees of 28 adult patients with OA at the time of total knee arthroplasty were used for the study. Degeneration was histologically assessed using a grading system. Expressions of Scleraxis (as a ligament cell marker) and Sry-type HMG box 9 (SOX9) (as a chondrogenic marker) were immunohistochemically assessed in each grade. RESULTS: We found the opposite expression pattern between Scleraxis and SOX9 according to the grade. The percentage of Scleraxis-positive cells decreased significantly by grade (60.9±23.7 in grade 1, 39.7±30.5 in grade 2, and 13.9±27.1 in grade 3, P<0.0001). In contrast, the percentage of SOX9-positive cells increased significantly by grade (2.5±4.9 in grade 1, 17.5±13.4 in grade 2, and 50.9±27.1 in grade 3, P<0.0001). Furthermore, co-localized expression of both Scleraxis and SOX9 was demonstrated in chondrocyte-like cells. CONCLUSIONS: This study indicates that chondrogenic differentiation is associated with the progression of degeneration in human ligaments. Our results suggest that the expression of SOX9 as a chondrogenic marker could be an indicator for the extent of degeneration in human ligaments. It remains to be elucidated whether suppression of chondrogenic differentiation can prevent progression of the degenerative process of cruciate ligaments in patients with OA.

The relationship between recurrences and immunosuppression on living donor liver transplantation for hepatocellular carcinoma.

OBJECTIVES: Living donor liver transplantation (LDLT) offers timely transplantation for patients with hepatocellular carcinoma (HCC). If ABO-incompatible LDLT is feasible, the needs for pretransplantation treatments may be eliminated. It is known that negative impacts of immunosuppression are limited among LDLT for HCC, however, we believe that excessive immunosuppression is one of the risk factors for recurrence. We compared the impacts of immunosuppression for LDLT with hepatectomy outcomes for HCC. METHODS: From 1991 to 2010, we performed 144 LDLTs including 14 patients with HCC. Seven met the Milan criteria. Immunosuppressive therapies were based on tacrolimus plus methylprednisolone plus CD25 antibody. For ABO-incompatible cases, we also used mycophenolate mofetil and rituximab. Five cases underwent strong imunosuppressive therapy (steroid pulse or rituximab) within 180 days. In addition, we performed hepatectomy for 180 HCC cases from 1997 to 2010. RESULTS: Overall survival rates of the LDLT cohort and hepatectomy groups were similar, but disease-free 5-year survival rates (DFS) of the LDLT cohort were significantly better than those of the hepatectomy group (total = 54.4% versus 27.4%, within the Milan criteria cases, 71.4% versus 33.8%). Thus, the negative impact of immunosuppression on recurrence was less than the benefit of a whole liver resection. Among strongly immunosuppressed cases, 5-years DFS rates were significantly worse than among other immunosuppressed cases (20.0% versus 76.2%). Upon univariate analysis, the factors associated with HCC recurrence were alpha-fetoprotein levels and steroid doses within 180 days, but multivariate analysis did not show a predictor for recurrence. CONCLUSION: Patients who are strongly immunosuppressed may have several negative impacts for recurrences. More careful indications must be selected for ABO-incompatible cases.

Recombinant human soluble thrombomodulin (ART-123) prevents warm ischemia-reperfusion injury in liver grafts from non-heart-beating donors.

BACKGROUND: Liver transplantation is an established treatment for end-stage liver disease. However, an ongoing problem worldwide concerning this treatment is the shortage of grafts. Although transplantation using grafts from non-heart-beating donors (NHBDs) is considered a promising solution, some researchers have reported that these liver grafts are associated with primary graft nonfunction and biliary complications. The purpose of this study was to establish a safe technique procuring liver grafts from marginal donors such as NHBDs. MATERIALS AND METHODS: Male Wistar rats were divided into three groups: (1) the heart-beating (HB) group, whose livers were retrieved from HB donors; (2) the non-HB (NHB) group, whose livers were retrieved from NHBDs that had experienced an apnea-induced agonal condition (for this group, livers were subjected to warm ischemia for 30 minutes after cardiac arrest); and (3) the recombinant human soluble thrombomodulin (ART-123) group, whose livers were retrieved in the same manner as the NHB group but pretreated with ART-123 (1 mg/kg) at the agonal stage. The livers were reperfused for 60 minutes with oxygenated Krebs-Henseleit bicarbonate buffer after cold preservation for 6 hours. RESULTS: Bile production and portal flow volume in the ART-123 group were significantly higher than those in the NHB group. Alanine aminotransferase levels in the ART-123 group were significantly lower than those in the NHB group. Histological findings showed the narrowing of sinusoidal spaces and necroses in the NHB group were more severe than those in the ART-123 group. CONCLUSIONS: These results suggest that thrombomodulin may improve the viability of liver grafts from NHBDs.

Navigated opening wedge high tibial osteotomy improves intraoperative correction angle compared with conventional method.

PURPOSE: The correction angle after high tibial osteotomy (HTO) depends on an accurate preoperative planning and an accurate intraoperative technique. We hypothesized that the use of a navigation system in opening wedge HTO would improve the intraoperative target angles in the coronal and sagittal planes. METHODS: Postoperative femoro-tibial angle (FTA) and tibial posterior slope (TPS) in 28 knees with navigated opening wedge HTO were compared to those in 31 knees with the conventional method. Intraoperative correction angle was determined by the predicted medial opening width in the conventional group, and by the change of hip-knee-ankle angle in the navigated group. We defined lateral unstable knee as the knees with lateral cortex breakage or lateral tibial plateau fracture. RESULTS: Mean postoperative FTA was higher in the conventional group than in the navigated group (P < 0.037). In the conventional group, 4 lateral unstable knees were corrected to 174.6°. In the navigated group, 5 lateral unstable knees were corrected to 170.3° and no knees showed FTA > 173°. Mean change in TPS was greater in the conventional group than in the navigated group (P = 0.001). CONCLUSION: The navigation system in opening wedge HTO might reduce undercorrection in the knees with lateral cortex breakage or lateral tibial plateau fracture, and provide the better intraoperative FTA and TPS. LEVEL OF EVIDENCE: III.

Nonmarginal-donor duodenal ulcers caused by rejection after simultaneous pancreas and kidney transplantation: a case report.

OBJECTIVE: Pancreas transplantation has been associated with the highest surgical complication rate among routinely performed organ transplant procedures. Complications can be caused not only from the pancreas itself but also from the simultaneously transplanted duodenum: gastrointestinal bleeding, duodenal ulcer, pseudoaneurysm, arterioenteric fistula, and severe rejection. Herein we report a patient who underwent simultaneous pancreas-kidney transplantation (SPKT) and experienced a duodenal perforation because of rejection. METHODS: The 60-year-old man with insulin-dependent diabetes underwent SPKT with enteric drainage. At 15 days there after he displayed melena. RESULTS: We suspected it to be caused by rejection and ischemic changes. We slightly increased the doses, of tacrolimus and methylprednisolone. But 17 days after SPKT, the ulcer perforated, requiring a repair operation and increased dose of mycophenolate mofetil. However, the ulcers perforated repeatedly, requiring 4 repair operations. Unfortunately the patient developed pneumonia that mitigated continues repairs or rejection therapies, so we expated the duodenum and pancreas but saved the kidney. The pathologic findings showed the ulcer to have been caused by severe rejection. Despite those episodes, the patient was weaned from hemodialysis. CONCLUSIONS: Perforation of the transplanted duodenum is one of the most difficult complications among SPKT patients. This potentially lethal complication may be caused by mucosal rejection, ischemic changes, and the exocrine output from the pancreatic graft.

Rituximab therapy and reduction of immunosuppression to rescue graft function after renal posttransplantation lymphoproliferative disorder found by macrohematuria in a pancreas and kidney transplant recipient: a case report.

INTRODUCTION: Posttransplantation lymphoproliferative disorder (PTLD) remains an uncommon complication of solid organ transplantation, with a high mortality rate reported after conventional therapies. Epstein-Barr virus (EBV) may cause PTLD, but most EBV infections after transplantation are clinically silent reactivations, so the detection of PTLD is often delayed. Recently we experienced the rare case of intrarenal graft PTLD found by macrohematuria in a simultaneous pancreas and kidney transplant recipient. The grafts were saved by treatments with rituximab, cyclophosphamide, hydroxydaunorubicin, and prednisone-based chemotherapy (R-CHOP) after reduction of immunosuppression (IR). METHODS: This 37-year-old man with insulin-dependent diabetes underwent simultaneous pancreas and kidney transplantation (SPK) with enteric drainage. Six months after transplantation, he displayed macrohematuria, which we investigated by blood tests, computer tomography (CT) scan, positron emission tomography (PET)-CT, and magnetic resonance imaging, recognizing a tumor in the transplanted renal graft. An open biopsy showed a CD20-positive PTLD. We started treatments with IR, rituximab (375 mg/m(2), weekly for 2 cycles) and R-CHOP therapy: rituximab (375 mg/m(2)) plus CHOP every 3 weeks for 6 cycles. RESULTS: IR and R-CHOP therapy achieved a complete remission (CR). CR has continued for 14 months at the time of writing. The maximum level of EBV DNA was 259 copies/µg DNA, but 2 months after these therapies, the level had decreased to normal. The patient had no impairment of pancreas and kidney graft functions. CONCLUSIONS: The outcome of intragraft PTLD in the kidney of an SPK recipient suggested that the negative impact of IR on graft function may be compensated by the immunosuppressive effects of rituximab, allowing reduced immunosuppression during chemotherapy.

Effects of mechanical stress on cytokine production in mandible-derived osteoblasts.

OBJECTIVE: Mechanical stress is known to be an important factor in the regulation of bone remodeling, and mandibular bone is continuously exposed to mechanical stressors such as occlusal force. Therefore, in this study, we investigated the effects of mechanical stress approaching occlusal force, to which mandible-derived osteoblasts (MDOB) are exposed, on cytokine expression and production using an original hydrostatic pressure apparatus. MATERIALS AND METHODS: The levels of cytokine in MDOB were examined by real-time RT-PCR, ELISA, and western blotting. In addition, mitogen-activated protein kinase inhibitor for ERK1/2, JNK, and p-38 pathways was used to identify the signal transduction pathway. RESULTS: Hydrostatic pressure increased the expression of IL-6 and TNF-α mRNA in a magnitude- and time-dependent manner and also enhanced IL-6 and TNF-α protein production. Furthermore, hydrostatic pressure changed the RANKL/OPG ratio in favor of RANKL for both mRNA and protein levels. Specific inhibitor of p-38 pathway but not that of the ERK1/2 and JNK pathways suppressed the up-regulation of RANKL production induced by hydrostatic pressure loading. CONCLUSION: These results suggest that MDOB play a role in cytokine production in response to mechanical stress and that occlusal force may support the maintenance of mandible bone homeostasis by activating bone remodeling through osteoclastogenesis.

Perfusion using oxygenated buffer containing prostaglandin E1 before cold preservation prevents warm ischemia-reperfusion injury in liver grafts from non-heart-beating donors.

We have previously reported that perfusion using warm oxygenated buffer before cold preservation (preperfusion) improved the viability of liver grafts from non-heart-beating donors. We demonstrated that adenosine triphosphate content was restored and apoptosis was reduced. The objective of the present study was to evaluate mitochondrial functions after this preperfusion and the effects of addition of prostaglandin E(1) (PGE(1)) to the preperfusion buffer. Preperfusion improved portal flow, bile production, and mitochondrial function, and reduced alanine aminotransferase levels in the perfusate. Addition of PGE(1) significantly increased bile production and suppressed alanine aminotransferase and tumor necrosis factor-α levels. PGE(1) minimized mitochondrial membrane damage and ischemic injury after liver graft reperfusion. Release of mitochondrial cytochrome c was suppressed by addition of PGE(1). In conclusion, perfusion using oxygenated buffer containing PGE(1) before cold preservation significantly prevented cellular damage, protected mitochondrial function, and suppressed the release of mitochondrial cytochrome c in livers undergoing warm ischemia-reperfusion injury. This method shows promise for reducing cellular damage in non-heart-beating donor liver grafts.

Signaling pathway on the effect of oxygenated warm perfusion prior to cold preservation of the liver grafts from non-heart-beating donors, and the additive effect of edaravone.

We have previously reported that oxygenated warm perfusion prior to cold preservation (preperfusion) improved the function and viability of liver grafts from non-heart-beating donors (NHBD) using an ex vivo perfusion model. In this study, we evaluated the signaling pathway underlying these effects as well as the additive effect of preperfusion administration of edaravone, a free radical scavenger. Preperfusion treatment suppressed activation of JNK, p38 MAPK, and ERK. The addition of edaravone provided an insignificant increase in bile production and a trend to a decrease in TUNEL-positive cells. Oxygenated perfusion prior to cold preservation improved the function and viability of the grafts from NHBD, which accompanied impairment of MAPK activation. Moreover, the addition of edaravone significantly enhanced the effects of preperfusion.

Management of living donor liver transplant patients using twice-daily 4-hour intravenous cyclosporine therapy.

Oral administration of cyclosporine (CsA) is the currently favored route in most liver transplant centers. From October 1998 to January 2008, 86 living donor liver transplantations (LDLTs) were performed in 85 patients (46 adults and 39 children) at our institution. Seventy-three patients received tacrolimus (Tac), and 12 intravenous CsA twice daily at a dose of 3 mg/kg/d as a 4-hour continuous infusion. Thirteen of 73 Tac-based patients were switched to CsA because of side effects. Five were switched to intravenous CsA because they were unable to take the drug orally because of severe Tac-related complications. The remaining eight patients switched to oral CsA. We evaluated patients (11 adults and three children), including 12 with induction therapy and two with conversion therapy within 2 weeks of LDLT. The patients were given a 4-hour intravenous infusion of CsA at an initial dose of 3 mg/kg/d. Stable and adequate blood CsA concentrations were achieved by 4-hour intravenous CsA administration. Among several factors, only graft-to-recipient weight ratio (r = .743, P < .0001) showed significant correlations with initial blood CsA concentration. No adverse effects were observed after intravenous CsA. No patients developed biopsy-proven acute cellular rejection (ACR) during intravenous CsA administration, whereas two patients had histopathologically diagnosed episodes of ACR after conversion from intravenous to oral CsA. Our findings suggest that immediate administration of a 4-hour intravenous infusion of CsA at an initial dose of 3 mg/kg/d is practical and effective for routine clinical use.