Brief Report: Highly motile cells are metabolically responsive to collagen density

Altered tissue mechanics and metabolism have gained significant attention as drivers of tumorigenesis, and mechanoresponsive metabolism has been implicated in migration and metastasis. However, heterogeneity in cell populations makes it difficult to link changes in behavior with metabolism, as individual cell behaviors are not necessarily reflected in population-based measurements. As such, the impact of increased collagen deposition, a tumor-associated collagen signature, on metabolism remains ambiguous. Here, we utilize a wide range of collagen densities to alter migration ability and study the bioenergetics of individual cells over time. Sorting cells based on their level of motility revealed energetics are a function of collagen density only for highly motile cells, not the entire population or cells with low motility. Changes in migration with increasing collagen density were correlated with cellular energetics, where matrix conditions most permissive to migration required less energy usage during movement and migrated more efficiently. These findings reveal a link between matrix mechanics, migratory phenotype, and bioenergetics and suggest that energetic costs are determined by the extracellular matrix and influence cell motility.     

Management of Hepatocellular Carcinoma Recurrence After Liver Transplantation

Management of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (OLT) is not well established. We conducted a retrospective analysis of our results in the treatment of HCC recurrence after OLT Patients. The 23 HCC recurrences developed after 182 OLT performed for HCC within Milan criteria, had an average follow-up of 60 months.

Results

The median time to recurrence was 23.4 months. Surgical resection of the recurrence was possible in 11 patients, but an R-0 resection was obtained in 8 patients. Four of these 8 patients developed another recurrence, with 3 succumbing due to tumor recurrence and 1 alive at 12 months with recurrence. The other 4 patients without recurrences, include 3 who are alive at 19, 31, and 86 months and 1 who died at 32.6 months due to hepatitis C recurrence. The 3 patients with palliative resections developed recurrences. Twelve patients were rejected for surgery: 8 were treated symptomatically, 2 with systemic chemotherapy, and 2 with everolimus and sorafenib. This last treatment was also prescribed for 2 patients after R-0 surgery who are alive at 19 and 31 months and for 1 patient after R-1 surgery who is alive at 19 months. Of 15 patients who died, 13 succumbed to HCC recurrence. The average survival from transplantation was 61.7 ± 37.5 and 48 ± 34.3 months for patients without and with recurrence, respectively (P < .001). The survival from the recurrence was significantly higher among patients with R-0 surgery: 32.3 ± 21.5 versus 11.9 ± 6.9 months (P = .006).

Conclusions

HCC recurrence after OLT of patients within Milan criteria was low but had a great impact on survival. Few cases are amenable to R-0 resection, but when possible it was associated with a significantly increased survival, although with an high incidence of a new recurrence. There is a rationale for the use of sorafenib and mammalian target of rapamycin based immunosuppression, which warrants randomized studies.     

TWEAK, a multifunctional cytokine in kidney injury

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a cytokine of the TNF superfamily that activates the Fn14 receptor. TWEAK may regulate cell proliferation, cell death, cell differentiation, and inflammation. TWEAK and Fn14 are constitutively present in the kidney. Sources of TWEAK and Fn14 include intrinsic renal cells and infiltrating leukocytes. Basal Fn14 expression is low, but Fn14 is greatly upregulated during kidney injury. TWEAK contributes to kidney inflammation promoting chemokine secretion by renal cells through canonical and non-canonical NFκB activation. TWEAK also promotes tubular cell proliferation. However, TWEAK induces mesangial and tubular cell apoptosis under proinflammatory conditions. These data indicate that TWEAK is a multifunctional cytokine in the kidney, the actions of which are modulated by the cell microenvironment. Confirmation of the role of TWEAK in kidney injury came from functional studies in experimental animal models. The TWEAK/Fn14 pathway contributed to cell death and interstitial inflammation during acute kidney injury, to glomerular injury in lupus nephritis, to hyperlipidemia-associated kidney injury, and to tubular cell hyperplasia following unilateral nephrectomy. Circulating soluble TWEAK (sTWEAK) levels are a potential biomarker of adverse outcomes in chronic kidney disease and urinary sTWEAK is a potential biomarker of lupus nephritis activity. The available evidence suggests that TWEAK may provide diagnostic information and be a therapeutic target in renal injury. Its role in human kidney disease should be further explored.     

Venous outflow obstruction after orthotopic liver transplantation: use of a breast implant to maintain graft position

Hepatic venous outflow obstruction (HVOO) is a rare complication after orthotopic liver transplantation (OLT) usually related to technical issues or to malposition or kinking of the hepatic graft. When HVOO is diagnosed during the early post-transplant period, surgical options are technically very demanding and outcomes discouraging. Therefore, angioplasty and stent placement have been indicated to avoid a chronic lesion of the graft. Three cases of HVOO after OLT are reported. HVOO was diagnosed during the early post-transplant period and was due to graft malposition in two patients and kinking of the vena cava anastomosis in one. All patients were successfully treated with a 300-cc gel-filled breast implant surgically placed in the right hepatic fossa with the liver graft resting on it. Massive ascites in all three patients disappeared and renal impairment resolved within two wk post-implant placement. No prosthesis-related complications have been observed after a follow-up ranging from 30 to 58 months. We describe a simple and effective method of maintaining the liver graft in an adequate position to achieve prolonged relief of the outflow obstruction for the whole graft and discuss the advantages of a breast implant over stent placement or the use of different balloon catheters.     

The effect of anesthetic technique on recovery from neuromuscular blockade with cisatracurium

OBJECTIVES: To assess the effect of four anesthetic techniques on recovery after a single dose of 0.2 mg/kg of cisatracurium. PATIENTS AND METHOD: After giving informed consent, 96 patients of both sexes, ASA I-III, were enrolled. Anesthesia was induced with fentanyl, propofol O2-N2O (FiO2 40%) after which the patients were randomly assigned to four groups according to maintenance technique: propofol by infusion, sevoflurane, desflurane or isoflurane at 1.3 MAC. Neuromuscular block was monitored (electromyographic recording of the pollicis adductor). Variables recorded were time of maximum block, duration of action of 1% and 25%, and recovery indices at T0-TR75 andT25%-T75%. ANOVA was performed ( = 0.05 and beta = 0.1). RESULTS: The groups were homogeneous. Time until recovery of 25% of baseline amplitude of the first response to a train of four (TOF) (T1) was longer in the desflurane group (68.4 +/- 11.1 min) than in the propofol group (60.2 +/- 9.4 min; p < 0.05). Time until recovery of 75% of the TOF-ratio was longer in the sevoflurane (96.8 +/- 13.1 min), desflurane (101.5 +/- 14.4 min) and isoflurane (94.1 +/- 13.9 min) groups than in the propofol group (83.7 +/- 1.3 min) (p < 0.0001).Times until recovery of T1 up to 1% were not statistically different: 45.8 +/- 10.7 (propofol), 50.6 +/- 11.0 (sevoflurane), 51.3 +/- 11.5 (desflurane) and 46.5 +/- 11.2 min (isoflurane). The 25% - 75% recovery index was also similar at 19.0 +/- 9.3 (propofol), 20.0 +/- 5.1 (sevoflurane), 25.7 +/- 12.4 (desflurane) and 20.9 +/- 7.9 (isoflurane). CONCLUSIONS: The inhaled anesthetics studied prolong the duration of clinical effect of cisatracurium more than does propofol.     

Das neue österreichische Patientenverfügungsrecht

Austria’s new Living Wills Act (Patientenverfügungsgesetz, or PatVG) that came into effect on 1st of June 2006, is the first law in Austria to regulate the controversial issue of living wills. The PatVG provides for a right to refuse future medical treatment by making an advance directive in the form of a living will that is either binding or “to be taken into consideration”. However, the establishment of a binding living will is governed by strict criteria as regards form and content, and both a medical doctor and a legal expert must be involved. Compliance with a living will is not allowed where there is a legal obligation to give medical treatment. There is also a legal obligation to give medical treatment in emergency situations where the time involved in looking for a living will could seriously endanger the health or the life of a patient.     

Straßenverkehrsrecht und Rettungsdienst

Legal uncertainties for emergency vehicle drivers can be avoided when fundamental rules are established. In particular, differentiation of special rights and rights of way is essential. Inherent in both is the urgency necessary to save human lives. The right of way signaled by flashing blue lights and siren does not however justify traffic violations but signifies rather a request to other traffic participants. In contrast, special rights require no announcement and constitute a justifiable reason for traffic violations. Even so they do not allow that other traffic participants be endangered or harmed. Adherence to these basic principles can prevent legal misinterpretations as well as rigid adoption of inflexible standards of behavior.