Expanding the evidence base in transplantation: the complementary roles of randomized controlled trials and outcomes research

Transplantation offers a unique opportunity to demonstrate the complementary roles of randomized controlled trials and outcome research. The surgery and collaboration necessary for the transplant procedure makes randomization and blinding difficult. Because essentially every recipient is included in a transplant registry, sampling bias is minimized. Regulatory agencies generally do not consider outcomes research when assessing efficacy of new drugs or medical interventions. This workgroup summary examines the suitability of outcomes research to complement results of randomized controlled trials and related issues: efficacy versus effectiveness, internal versus external validity, data types, limitations, and analysis methodologies. Many advances in outcomes research have been pioneered in transplantation. A case is made for regulatory and reimbursement authorities to use outcomes research when making efficacy, effectiveness, and coverage decisions in transplantation.     

Risk of stroke for carotid endarterectomy patients with contralateral carotid occlusion

The role of a contralateral carotid occlusion in the appearance of neurological complications after carotid endarterectomy (CEA) operations is a matter of some debate. In the North American Symptomatic Carotid Endarterectomy Trial, the risk of perioperative stroke was found to be higher in patients with a contralateral carotid occlusion. In a literature survey in 2004, however, a significantly increased risk of perioperative stroke was found in only one out of 17 studies on contralateral carotid occlusion patients. We therefore examined the frequency of stroke in patients with contralateral carotid occlusion at our own institution and performed a meta-analysis based on 19 representative studies, including the data from our own institution. Out of 1,960 CEAs at the authors' institute, a significantly higher frequency of 5.6% compared to 2.1% (p = 0.012) for perioperative stroke risk was seen in patients with contralateral carotid occlusion compared to those without. The meta-analysis, based on 19 studies, also showed in 13,438 CEA operations a significantly higher perioperative stroke rate of 3.7% compared to 2.4% (p = 0.002) in the presence of a contralateral carotid occlusion. Nevertheless, due to the extremely poor outcomes of medically treated symptomatic patients, a surgical or endovascular procedure should be sought for these patients. Since the superiority of angioplasty/stent procedures has not yet been verified compared to surgical procedures in these patients, special indication for an endovascular procedure should also be taken into consideration.     

Excelsione, a depsidone from an endophytic fungus isolated from the New Zealand endemic tree Knightia excelsa

A new tetracyclic depsidone, excelsione (1), was isolated from the extract of an unidentified fungal endophyte obtained from the New Zealand endemic tree Knightia excelsa. The structure was elucidated by X-ray crystallography and NMR spectroscopy.     

Instep free flap for plantar soft tissue reconstruction: indications and options

Pedicled instep flaps are frequently used in weight-bearing plantar reconstruction, but may not be available after severe foot injuries. Although free instep flaps offer a viable option, they have scarcely been reported. A posttraumatic plantar forefoot defect was reconstructed with a sensate, instep free flap, because local flaps were not available and defect size did not require a distant free flap, and the current literature was reviewed for therapeutic options. The instep free flap yielded an excellent functional and aesthetic long-term result. In the literature, pedicled instep flaps are advocated for moderate size defects of the weight-bearing heel and sole, while free flaps from distant sites are preferred for large defects. Although skin-grafted muscle flaps and fasciocutaneous flaps yield similar results, reconstruction by like tissues appears favorable. We suggest the instep free flap for weight-bearing plantar foot reconstruction, when pedicled instep flaps are not available and distant free flaps are avoidable.     

The thuggacins, novel antibacterial macrolides from Sorangium cellulosum acting against selected Gram-positive bacteria

In our screening program we found an activity against some Gram-positive bacteria, including mycobacteria in the culture supernatant of Sorangium cellulosum strain So ce895. The antibiotic responsible for this activity was isolated and named thuggacin. Initial studies towards the mechanism of action showed that thuggacin A inhibits a late step of the respiratory chain of some bacteria.     

Structure, derivatization, and antitumor activity of new griseusins from Nocardiopsis sp

Four new griseusins, 4'-dehydro-deacetylgriseusin A (1) and 2a,8a-epoxy-epi-deacetylgriseusin B (2) as new constitutional derivatives and epi-deacetylgriseusin A (3) and epi-deacetylgriseusin B (4) as new stereoisomers, were isolated from Nocardiopsis sp. (YIM80133, DSM16644). 4'-Dehydro-deacetylgriseusin A (1) showed pronounced cytotoxic potency (mean IC50 = 0.430 microM) combined with a significant selectivity for mammary cancer, renal cancer, and melanoma in a panel consisting of 37 tumor cell lines. In a clonogenic assay with tumor cells from 51 solid tumors, 1 inhibited anchorage independent growth and in vitro colony formation of tumor cells in a concentration-dependent and tumor type selective manner. As 1 was only a minor product, a semisynthetic preparation from the major metabolite, epi-deacetylgriseusin A (3), was achieved. Our studies also yielded 9-hydroxy-epi-deacetylgriseusin B methylester (5), 4'-dehydro-9-hydroxy-deacetylgriseusin B methylester (6), and 4'-dehydro-2a,8a-epoxy-deacetylgriseusin B (7) as new synthetic isochromanequinone derivatives, which provided a basic structure-activity relationship study.     

Median Frequency Revisited: An Approach to Improve a Classic Spectral Electroencephalographic Parameter for the Separation of Consciousness from Unconsciousness

Background: In the past, several electroencephalographic parameters have been presented and discussed with regard to their reliability in discerning consciousness from unconsciousness. Some of them, such as the median frequency and spectral edge frequency, are based on classic spectral analysis, and it has been demonstrated that they are of limited capacity in differing consciousness and unconsciousness.

Methods: A generalized approach based on the Fourier transform is presented to improve the performance of electroencephalographic parameters with respect to the separation of consciousness from unconsciousness. Electroencephalographic data from two similar clinical studies (for parameter development and evaluation) in adult patients undergoing general anesthesia with sevoflurane or propofol are used. The study period was from induction of anesthesia until patients followed command after surgery and includes a reduction of the hypnotic agent after tracheal intubation until patients followed command. Prediction probability was calculated to assess the ability of the parameters to separate consciousness from unconsciousness.

Results: On the basis of the training set of 40 patients, a new spectral parameter called weighted spectral median frequency was designed, achieving a prediction probability of 0.82 on the basis of the "classic" electroencephalographic frequency range up to 30 Hz. Next, in the evaluation data set, the prediction probability was 0.79, which is higher than the prediction probability of median frequency (0.58) or spectral edge frequency (0.59) and the Bispectral Index (0.68) as calculated from the same data set.