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).     

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     

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.     

Plasmin in Nephrotic Urine Activates the Epithelial Sodium Channel

Proteinuria and increased renal reabsorption of NaCl characterize the nephrotic syndrome. Here, we show that protein-rich urine from nephrotic rats and from patients with nephrotic syndrome activate the epithelial sodium channel (ENaC) in cultured M-1 mouse collecting duct cells and in Xenopus laevis oocytes heterologously expressing ENaC. The activation depended on urinary serine protease activity. We identified plasmin as a urinary serine protease by matrix-assisted laser desorption/ionization time of-flight mass spectrometry. Purified plasmin activated ENaC currents, and inhibitors of plasmin abolished urinary protease activity and the ability to activate ENaC. In nephrotic syndrome, tubular urokinase-type plasminogen activator likely converts filtered plasminogen to plasmin. Consistent with this, the combined application of urokinase-type plasminogen activator and plasminogen stimulated amiloride-sensitive transepithelial sodium transport in M-1 cells and increased amiloride-sensitive whole-cell currents in Xenopus laevis oocytes heterologously expressing ENaC. Activation of ENaC by plasmin involved cleavage and release of an inhibitory peptide from the ENaC γ subunit ectodomain. These data suggest that a defective glomerular filtration barrier allows passage of proteolytic enzymes that have the ability to activate ENaC.Nephrotic syndrome is characterized by proteinuria, sodium retention, and edema. Increased renal sodium reabsorption occurs in the cortical collecting duct (CCD),^1,2 where a rate-limiting step in transepithelial sodium transport is the epithelial sodium channel (ENaC), which is composed of the three homologous subunits: α, β, γ.³ENaC activity is regulated by hormones, such as aldosterone and vasopressin (AVP)^4,5; however, adrenalectomized rats and AVP-deficient Brattleboro rats are capable of developing nephrotic syndrome,^1,6 and nephrotic patients do not consistently display elevated levels of sodium-retaining hormones,^7,8 suggesting that renal sodium hyper-reabsorption is independent of systemic factors. Consistent with this, sodium retention is confined to the proteinuric kidney in the unilateral puromycin aminonucleoside (PAN) nephrotic model.^2,9,10There is evidence that proteases contribute to ENaC activation by cleaving the extracellular loops of the α- and γ-subunits.^11–13 Proteolytic activation of ENaC by extracellular proteases critically involves the cleavage of the γ subunit,^14–16 which probably leads to the release of a 43-residue inhibitory peptide from the ectodomain.¹⁷ Both cleaved and noncleaved channels are present in the plasma membrane,^18,19 allowing proteases such as channel activating protease 1 (CAP1/prostasin),²⁰ trypsin,²⁰ chymotrypsin,²¹ and neutrophil elastase²² to activate noncleaved channels from the extracellular side.^23,24 We hypothesized that the defective glomerular filtration barrier in nephrotic syndrome allows the filtration of ENaC-activating proteins into the tubular fluid, leading to stimulation of ENaC. The hypothesis was tested in the PAN nephrotic model in rats and with urine from patients with nephrotic syndrome.     

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.     

Estimation of the time since death—reconsidering the re-establishment of rigor mortis

In forensic medicine, there is an undefined data background for the phenomenon of re-establishment of rigor mortis after mechanical loosening, a method used in establishing time since death in forensic casework that is thought to occur up to 8 h post-mortem. Nevertheless, the method is widely described in textbooks on forensic medicine. We examined 314 joints (elbow and knee) of 79 deceased at defined time points up to 21 h post-mortem (hpm). Data were analysed using a random intercept model. Here, we show that re-establishment occurred in 38.5% of joints at 7.5 to 19 hpm. Therefore, the maximum time span for the re-establishment of rigor mortis appears to be 2.5-fold longer than thought so far. These findings have major impact on the estimation of time since death in forensic casework.     

Tumour volume delineation in prostate cancer assessed by [11C]choline PET/CT: validation with surgical specimens

Purpose

PET has been proven to be helpful in the delineation of gross tumour volume (GTV) for external radiation therapy in several tumour entities. The aim of this study was to determine if [¹¹C]choline PET could be used to localize the carcinomatous tissue within the prostate in order to specifically target this area for example with high-precision radiation therapy.

Methods

Included in this prospective study were 20 patients with histological proven prostate carcinoma who underwent [¹¹C]choline PET/CT before radical prostatectomy. After surgical resection, specimens were fixed and cut into 5-mm step sections. In each section the area of the carcinoma was delineated manually by an experienced pathologist and digitalized, and the histopathological tumour volume was calculated. Shrinkage due to resection and fixation was corrected using in-vivo and ex-vivo CT data of the prostate. Histopathological tumour location and size were compared with the choline PET data. Different segmentation algorithms were applied to the PET data to segment the intraprostatic lesion volume.

Results

A total of 28 carcinomatous lesions were identified on histopathology. Only 13 (46 %) of these lesions had corresponding focal choline uptake. In the remaining lesions, no PET uptake (2 lesions) or diffuse uptake not corresponding to the area of the carcinoma (13 lesions) was found. In the patients with corresponding PET lesions, no suitable SUV threshold (neither absolute nor relative) was found for GTV segmentation to fit the volume to the histological tumour volume.

Conclusion

The choline uptake pattern corresponded to the histological localization of prostate cancer in fewer than 50 % of lesions. Even when corresponding visual choline uptake was found, this uptake was highly variable between patients. Therefore SUV thresholding with standard algorithms did not lead to satisfying results with respect to defining tumour tissue in the prostate.     

Transcortical or transcallosal approach to ventricle-associated lesions: a clinical study on the prognostic role of surgical approach

Most entities in and around the anterior two-thirds of the supratentorial ventricles can be reached via transcortical or transcallosal approach. This study examined the effect of surgical approach on the postoperative neurological outcome. Thirty-eight patients with intra- and periventricular supratentorial lesions were operated on by either frontal transcortical or anterior transcallosal approach. Postoperative diencephalic damage occurred in 22% of patients in the transcortical group and in 36% in the transcallosal group; transient mutism was virtually equivalent in the two groups. Postoperative epilepsy (26%) and subdural fluid collections (30%) occurred only in the transcortical group. The incidence of postoperative hemiparesis was higher in the transcallosal group. There was a high correlation between postoperative Glasgow Outcome Score of 5 and preoperative severity of neurological disease but no correlation between postoperative Glasgow Outcome Score of 5 and location of the lesion or between postoperative clinical course and surgical approach. Surgical outcome of ventricle-associated lesions depends mainly on the severity of preoperative symptoms and not on surgical approach. Additionally, the incidence of postoperative seizures and subdural fluid collections after transcortical surgery is high.