Conversion to sirolimus of patients with chronic allograft nephropathy—a retrospective analysis of outcome and influencing factors

Purpose

The purpose of this study was to analyse the outcome and its influencing factors in patients whose therapy was converted from calcineurin inhibitors (CNI) to sirolimus (SRL) due to chronic allograft nephropathy (CAN).

Materials and methods

Therapies of 78 patients (44 men) with CAN from three European transplant centres were converted from CNI therapy to SRL and followed 24 months. Slopes for creatinine clearance before and after conversion were calculated. Influencing factors were analysed by a multivariance analysis.

Results

The slope of the creatinine clearance improved significantly (?0.90 vs. ?0.34 ml min^?1 month^?1; p?<?0.01). In patients whose therapy was converted from cyclosporine A (CyA) to SRL, the slope improved significantly, whereas conversion from Tacrolimus (Tac) to SRL did not affect the slope. The benefit was more pronounced in (1) patients with low or moderate baseline creatinine clearance, (2) patients receiving SRL after conversion without additional mycophenolate mofetil and (3) patients with low or moderate proteinuria.

Conclusion

Conversion from CyA to SRL but not from Tac to CRL is associated with a reduced loss of renal allograft function in patients with CAN.     

The Lymph Node Ratio is the Strongest Prognostic Factor after Resection of Pancreatic Cancer

Introduction  Survival after surgery of pancreatic cancer is still poor, even after curative resection. Some prognostic factors like the status of the resection margin, lymph node (LN) status, or tumor grading have been identified. However, only few data have been published regarding the prognostic influence of the LN ratio (number of LN involved to number of examined LN). We, therefore, evaluated potential prognostic factors in 182 patients after resection of pancreatic cancer including assessment of LN ratio. Methods  Since 1994, 204 patients underwent pancreatic resection for ductal pancreatic adenocarcinoma. Survival was evaluated in 182 patients with complete follow-up evaluations. Of those 182 patients, 88% had cancer of the pancreatic head, 5% of the body, and 7% of the pancreatic tail. Patients underwent pancreatoduodenectomy (85%), distal resection (12%), or total pancreatectomy (3%). Survival was analyzed by the Kaplan–Meier and Cox methods. Results  In all 204 resected patients, operative mortality was 3.9% (n = 8). In the 182 patients with follow-up, 70% had free resection margins, 62% had G1- or G2-classified tumors, and 70% positive LN. Median tumor size was 30 (7–80) mm. The median number of examined LN was 16 and median number of involved LN 1 (range 0–22). Median LN ratio was 0.1 (0–0.79). Cumulative 5-year survival (5-year SV) in all patients was 15%. In univariate analysis, a LN ratio ≥ 0.2 (5-year SV 6% vs. 19% with LN ratio < 0.2; p = 0.003), LN ratio ≥ 0.3 (5-year SV 0% vs. 18% with LN ratio < 0.3; p < 0.001), a positive resection margin (p < 0.01) and poor differentiation (G3/G4; p < 0.03) were associated with poorer survival. In multivariate analysis, a LN ratio ≥ 0.2 (p < 0.02; relative risk RR 1.6), LN ratio ≥ 0.3 (p < 0.001; RR 2.2), positive margins (p < 0.02; RR 1.7), and poor differentiation (p < 0.03; RR 1.5) were independent factors predicting a poorer outcome. The conventional nodal status or the number of examined nodes (in all patients and in the subgroups of node positive or negative patients) had no significant influence on survival. Patients with one metastatic LN had the same outcome as patients with negative nodes, but prognosis decreased significantly in patients with two or more LN involved. Conclusions  Not the lymph node involvement per se but especially the LN ratio is an independent prognostic factor after resection of pancreatic cancers. In our series, the LN ratio was even the strongest predictor of survival. The routine estimation of the LN ratio may be helpful not only for the individual prediction of prognosis but also for the indication of adjuvant therapy and herein related outcome and therapy studies. Presented in part at the 49th Annual Meeting of the Society for Surgery of the Alimentary Tract, May 2008 in San Diego and at the Annual Meeting of the German Cancer Society, February 2008 in Berlin, Germany     

Rotational instability of the knee: internal tibial rotation under a simulated pivot shift test

Introduction  Recently, several publications investigated the rotational instability of the human knee joint under pivot shift examinations and reported the internal tibial rotation as measurement for instrumented knee laxity measurements. We hypothesize that ACL deficiency leads to increased internal tibial rotation under a simulated pivot shift test. Furthermore, it was hypothesized that anatomic single bundle ACL reconstruction significantly reduces the internal tibial rotation under a simulated pivot shift test when compared to the ACL-deficient knee. Methods  In seven human cadaveric knees, the kinematics of the intact knee, ACL-deficient knee, and anatomic single bundle ACL reconstructed knee were determined in response to a 134 N anterior tibial load and a combined rotatory load of 10 N m valgus and 4 N m internal tibial rotation using a robotic/UFS testing system. Statistical analyses were performed using a two-way ANOVA test. Results  Single bundle ACL reconstruction reduced the anterior tibial translation under a simulated KT-1000 test significantly compared to the ACL-deficient knee (P < 0.05). After reconstruction, there was a statistical significant difference to the intact knee at 30° of knee flexion. Under a simulated pivot shift test, anatomic single bundle ACL reconstruction could restore the intact knee kinematics. Internal tibial rotation under a simulated pivot shift showed no significant difference in the ACL-intact, ACL-deficient and ACL-reconstructed knee. Conclusion  In conclusion, ACL deficiency does not increase the internal tibial rotation under a simulated pivot shift test. For objective measurements of the rotational instability of the knee using instrumented knee laxity devices under pivot shift mechanisms, the anterior tibial translation should be rather evaluated than the internal tibial rotation. This study was supported in part by a grant of the German Speaking Association of Arthroscopy (AGA).     

Impact of Intraoperative Parathyroid Hormone Levels on Surgical Results in Patients with Renal Hyperparathyroidism

The aim of our study was to evaluate the impact of intraoperative parathyroid hormone (PTH) measurement on surgical results in patients with renal hyperparathyroidism (HPT). From December 1999 to February 2004, a series of 95 consecutive patients underwent total parathyroidectomy and intraoperative PTH measurement for renal HPT. Intraoperative PTH was measured before and 15 minutes after parathyroidectomy with the Immulite DPC assay for intact PTH. The median PTH levels before surgery were 133.0 pmol/L, which declined to 5.9 pmol/L at the end of the operation. At follow-up, 91 of 95 (96%) patients presented with normal calcium levels. Persistent renal HPT was seen in three patients, and recurrent HPT was diagnosed in another. In 99% of the patients the intraoperative PTH levels declined more than 50% and in 73% the PTH decay was more than 90%. In 64% of the patients PTH levels dropped into the normal range (< 7.6 pmol/L). Altogether, 97% of the patients with an intraoperative PTH decrease of more than 90% presented with normal PTH levels postoperatively (p = 0.0237), as did all of the patients whose intraoperative PTH dropped into the normal range (p = 0.0432). Intraoperative PTH measurement with a decrease in intraoperative PTH of at least 90% is highly predictive of successful parathyroidectomy and normalization of postoperative calcium and PTH levels.     

Preliminary experience with oral dexmedetomidine for procedural and anesthetic premedication

BACKGROUND: Oral premedication is often required in children to provide anxiolysis and lessen the psychological impact of hospitalization and/or procedures. We present our experience with dexmedetomidine as an oral premedicant prior to procedural sedation or anesthetic induction. METHODS: We undertook a retrospective review of the anesthesia or sedation service records of patients who received oral dexmedetomidine. RESULTS: The cohort for the study included 13 patients ranging in age from 4 to 14 years. Oral dexmedetomidine (mean dose: 2.6 +/- 0.83 microg.kg(-1); range 1.0-4.2 microg.kg(-1)) was used as premedication prior to anesthesia induction in four patients and prior to intravenous (IV) cannula placement for procedural sedation in nine patients with neurobehavioral problems. Effective sedation was achieved in 11 of 13 patients. The one patient in whom anxiolysis was not achieved received the lowest dose of dexmedetomidine (1 microg.kg(-1)) prior to anesthesia induction. In the other three patients, parental separation and acceptance of the mask was achieved at 20-30 min with a dose of 2.5 microg.kg(-1). When used for procedural sedation, placement of an IV cannula was accomplished without difficulty in seven of eight patients with neurobehavioral disorders and with only mild resistance in the other. No complications were noted and parental satisfaction with the sedation experience was high. CONCLUSIONS: These preliminary data suggest that dexmedetomidine may be an effective oral premedicant prior to anesthesia induction or procedural sedation. We found that it was effective even in patients with neurobehavioral disorders in whom previous attempts at sedation had failed.     

术中三维图像导航下的经皮骶髂关节螺钉固定

目的 探讨术中三维图像导航下经皮骶髂关节螺钉固定术的使用技术.方法 16例骶骨骨折安装定位标记后三维C臂机扫描,获取骨盆三维图像,输出到导航设备后自动进行注册.根据导航探针的指示做皮肤小切口,运用导航电钻经皮钻孔后空心螺钉固定骶髂关节.术毕三维扫描r解内固定情况,术后CT扫描评价螺钉位置.结果 所有16例手术20枚螺钉均顺利植入,无术中及术后并发症,所有螺钉均固定至骶1椎体.手术时间平均80 min,术中放射时间平均1.13 min.4例进行了双侧骶髂关节螺钉固定,所需手术时间及术中透视时间较长.术毕三维扫描及术后CT扫描显示所有骨折或脱位复位后位置满意,螺钉的位置均满意.结论 术中三维图像导航下的骶髂关节螺钉固定术是可行的.虽然有术中图像质量相对CT较差、手术时间相对较长、需要导航设备等缺点,但相对于传统透视下的方法,它能减少手术中的放射量、提高手术的准确性,是一有效的临床新技术.     

Dereplication, residual complexity, and rational naming: the case of the Actaea triterpenes

The genus Actaea (including Cimicifuga) has been the source of ～200 cycloartane triterpenes. While they are major bioactive constituents of complementary and alternative medicines, their structural similarity is a major dereplication problem. Moreover, their trivial names seldom indicate the actual structure. This project develops two new tools for Actaea triterpenes that enable rapid dereplication of more than 170 known triterpenes and facilitates elucidation of new compounds. A predictive computational model based on classification binary trees (CBTs) allows in silico determination of the aglycone type. This tool utilizes the Me (1)H NMR chemical shifts and has potential to be applicable to other natural products. Actaea triterpene dereplication is supported by a new systematic naming scheme. A combination of CBTs, (1)H NMR deconvolution, characteristic (1)H NMR signals, and quantitative (1)H NMR (qHNMR) led to the unambiguous identification of minor constituents in residually complex triterpene samples. Utilizing a 1.7 mm cryo-microprobe at 700 MHz, qHNMR enabled characterization of residual complexity at the 10-20 μg level in a 1-5 mg sample. The identification of five co-occurring minor constituents, belonging to four different triterpene skeleton types, in a repeatedly purified natural product emphasizes the critical need for the evaluation of residual complexity of reference materials, especially when used for biological assessment.     

Molecular imaging reveals time course of matrix metalloproteinase activity in acute cutaneous vasculitis in vivo

Matrix metalloproteinases (MMPs) play a critical role in various pathological conditions including cutaneous inflammation. Thus far, serial assessment of MMP activity in ongoing inflammation is hampered due to technical limitations. Here, we present an innovative method for longitudinal detection of MMP activity by in vivo imaging. First, we analysed skin sections from patients suffering from leucocytoclastic vasculitis (LcV) and detected a significant MMP signal via immunofluorescence staining. Then, we mimicked LcV in mice in a well‐studied model of immune complex‐mediated vasculitis (ICV). This acute inflammatory process was serially visualized in vivo using the fluorescence‐labelled MMP tracer Cy5.5‐AF443. The deposition of fluorescence‐labelled immune complexes and MMP tracer distribution was visualized repeatedly and non‐invasively by fluorescence reflectance imaging. In correlation with the presence of MMP‐2 and MMP‐9 in immunofluorescence stainings, Cy5.5‐AF443 accumulated in ICV spots in the skin of C57BL/6 mice. This tracer accumulation could also be observed in mice equipped with a dorsal skinfold chamber, where microscopic observations revealed an increased recruitment of fluorescence‐labelled leucocytes during ICV. The specificity of the MMP tracer was supported by (i) analysis of mice deficient in functional β₂‐integrins (CD18^?/?) and (ii) subsequent MMP immunofluorescence staining. These findings let us conclude that MMP accumulation in the acute phase of ICV depends on β₂‐mediated leucocyte recruitment. In summary, we show that MMPs are involved in ICV as determined by Cy5.5‐AF443, a new optical marker to longitudinally and non‐invasively follow MMP activity in acute skin inflammation in vivo.