Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64.

Pecoraite, Ni6Si4O10(OH)8, Nickel Analog of Clinochrysotile, Formed in the Wolf Creek Meteorite.

Pecoraite is a new phase in the natural system H(2)O-NiO-MgOSiO(2), the nickel analog of clinochrysotile. It occurs in cracks in the Wolf Creek meteorite in Australia where it was formed under hydrothermal conditions. Particles of pecoraite are very small curved plates which have begun to coil; some have achieved spiral form.

Finite element analysis of a bone-implant system with the proximal femur nail.

Static analysis with finite element of a realistic femur nail bone-implant system in a typical proximal femoral fracture under physiological load bearing situations provides results for stress, displacement and strain. The question to be answered is, if simulation with the finite element analysis is able to explain biomechanically clinical observed patterns of failure. Surface-Reconstruction with CT database of a proximal femur and reconstruction with CT based density data was done. Next steps were to unite the bone structure with the Proximal Femoral Nail and to model two relevant fractures (31-A2.2 and A2.3 according AO). After modelling of geometry, isotropic material behaviour and load application numeric calculation of the femur-nail system with FE-software was performed. FE simulation mainly shows an axial dislocation of the femoral head screw with nearly no dislocation of the antirotation screw. This so-called z-effect therefore means: (1) Tilting of the proximal main fragment around the sagittal axis between the screws and (2) relative movement of both screws in the frontal plane. Relative movement of the two screws against each other could be the reason for implant failure, the so called cut out. Furthermore simulation shows different gliding of the screws explaining the so called z-telescoping. The analyzed stress patterns have to be relativized, because isotropic material behaviour of cancellous bone was assumed. Further examinations for this issue are necessary.

Percutaneous angioplasty for peripheral arterial occlusive disease. Correlates of clinical success.

We reviewed 142 percutaneous transluminal angioplasties (PTAs) in the iliac (n = 94) and femoropopliteal (n = 48) positions of 107 patients. Emphasis was placed on the ultimate clinical outcome, which was determined from a pool of clinical, hemodynamic, and angiographic data. Limb-threatening ischemia was the indication for intervention in 53% of the cases. The median follow-up interval was 17 months. Overall success was achieved in 50% of cases in both iliac and femoral positions at one year after PTA. The following factors were found to correlate with a successful clinical outcome: PTA for claudication vs limb-threatening ischemia (P less than .001); focal as opposed to diffuse stenosis or occlusion (P less than .02); immediate return of distal pulses (P less than .001); the absence of diabetes (P less than .05); and the presence of a patent outflow tract (P less than .001). Treatment results with PTA will vary widely according to the nature of the patient population and the criteria for determining success.

Hemodialysis graft salvage.

Hemodialysis access procedures account for a large percentage of patients undergoing surgical treatment. Salvage procedures are frequently used to extend the life of a thrombosed graft and thereby maximize the limited available access sites. Factors that may influence the success of salvage procedures, as well as the financial risk to benefit comparison, may be of increasing importance in the era of aggressive medical cost containment. The charts of 70 patients who underwent 116 thrombectomies or revisions of polytetrafluoroethylene (PTFE) hemodialysis arteriovenous grafts of the upper extremity for thrombosis were retrospectively analyzed. Patency of salvaged grafts by life-table analysis was 75.0 percent at two days, 45.0 percent at 30 days, 18.0 percent at 120 days and 2.5 percent at one year. Patency was 59 and 25 percent for revised grafts at 30 and 120 days, respectively, versus 30 and 10 percent at the same time intervals for thrombectomized grafts only. Minimum combined operative and hospital costs were $4,350 per salvage attempt. Salvage patency of PTFE dialysis grafts of the upper extremity was dismal, especially when thrombectomy alone was used. No specific patient factors were predictive of patency interval. Based upon these results, we cannot continue to recommend graft thrombectomy alone for thrombosed dialysis grafts. Because the poor results with graft revision as well, placement of a new graft without any attempt at salvage may be the best therapeutic and cost-effective option.

[X-ray crystallographic studies of diclofenac-sodium--structural analysis of diclofenac-sodium tetrahydrate]. / Röntgenkristallographische Untersuchungen an Diclofenac-Natrium--Strukturanalyse des Diclofenac-Natrium Tetrahydrat.

The crystal structure of the hydrate of the antiphlogistic drug diclofenac sodium was determined to explain the unusual dissolution behaviour in ethyl acetate. The compound crystallizes in the monoclinic space group P2(1)/m with a = 9.464(2), b = 39.405(7), c = 9.972(3) A und beta = 90.74(2) degrees. The unit cell contains two symmetry independent formula units (C14H10Cl2NO2)-Na+.3,94 H2O. There are molecule layers and sodium-water layers which show order-disorder phenomena.

[On the synthesis of compounds with beta-adrenergic activity (author's transl)]. / Zur Synthese von beta-adrenerg wirksamen Verbindungen.

It is reported of the synthesis of 1-phenoxy-2-hydroxy-3-aminopropane derivatives with different substituents in the phenoxy residue as well as in the amino group. The potency and the efficacy of these derivatives depend on the substituents. By the introduction of the arylamino-ethyl residue into the nitrogen atom, beta-adrenergic locking agents with marked agonistic activity are obtained.

[Derivatives of 6,7-dimethoxy-1-thiaisochroman-1,1-dioxide and 3.4-dihydro-6,7-dimethoxy-2H-1,2-benzothiazine-1,1-dioxide (author's transl)]. / Derivate von 6,7-Dimethoxy-1-thiaisochroman-1,1-dioxid und 3,4-Dihydro-6,7-dimethoxy-2H-1,2-benzothiazin-1,1-dioxid.

The authors deal with the synthesis of 3-substituted 6,7-dimethoxy-1-thiaisochroman-1,1-dioxide and 3,4-dihydro-6,7-dimethoxy-2H-1,2-benzothiazine-1,1-dioxide derivatives. The compounds in the first-named group were found to exert effects on the central nervous system, those produced by the basic amides being particularly marked, which differ from those of currently used psychopharmacological agents.

[Synthesis and anticonvulsant action of propranolol derivatives with a tertiary nitrogen atom]. / Synthese und antikonvulsive Wirkung von Propranololderivaten mit tertiärem Stickstoffatom.

Tertiary derivatives of the beta-receptorblocker propranolol were synthesized and pharmacologically tested for anticonvulsive activities. The results show that it is possible, to separate the beta-receptor blocking from the anticonvulsive activities by modifying the chemical structure.

[Potential cardiotonics. 7. Synthesis and cardiovascular effects of 5-(4-pyridinyl)-, 6-methyl-4-(4-pyridinyl) and 6-methyl-5-phenyl-substituted 3-cyano-2-aminoalkylamino-pyridines]. / Potentielle Kardiotonika. 7. Mitteilung5: Darstellung und kardiovaskuläre Eigenschaften von 5-(pyrid-4-yl)-, 6-methyl-5-(pyrid-4-yl)- und 6-methyl-5-phenyl-substituierten 2-Aminoalkylamino-3-cyan-pyridinen.

The title compounds were synthesized by treating of 2-chloro-pyridines 1-3 with the appropriate aminoalkylamines or piperazines. In isolated guinea pig atria some compounds showed greater positive inotropic activity than amrinone. Heart rate was decreased or remained unchanged. In anesthetized dogs some derivatives exerted a dose-dependent increase in myocardial contractility and, additionally, a decrease in blood pressure.

[The synthesis of 3-amino-5-(4-pyridinyl)-1,2-dihydropyrid-2-one (Cordemcura) from a technical mixture of pyridines]. / Untersuchungen zur Synthese von 3-Amino-5-(pyrid-4-yl)-1,2-dihydro-pyrid-2-on (Cordemcura) aus technischen Pyridinbasengemischen.

For preclinical and clinical research the headline compound 6 has been synthesized from pyrid-4-yl-malondialdehyde (3) and its bis-N,N-dimethyl)-aldimin-derivative 1 by cyclization with cyanoacetamide giving 4, partial hydrolysis to the amide 5, and degradation by sodiumhypochlorite to the amine 6, concerning to the way described in patent literature. Starting product was a mixture of alkyl pyridines from which 4-picoline reacted selectively with the Vilsmeyer-complex of phosgene/DMF to give cristalline 1. Optimization in all steps resulted in a procedure that gives us the intermediates in good yields and qualities and the final product 6 with high purity, suitable for pharmaceutical use.

[Quality management in the hospital]. / Qualitätsmanagement im Krankenhaus.

Quality management in hospitals is a much discussed topic. However, mainly theorists take the floor, who have some good advice, but rarely have practical experience. All those theorists have been heard by the responsible person of the Fritz-König-hospital in Bad Harzburg, as well. At the end, however, an own system of quality management was developed with the aid of an external expert. This article describes the step-by-step introduction of quality management and the related experiences.

[Dying through the hand of man or taken by the hand of man? Results of an opinion poll concerning active euthanasia and the Hospice Movement]. / An der Hand oder durch die Hand eines Menschen sterben? Ergebnisse einer Befragung zu Sterbehilfe und Hospizbewegung.

BACKGROUND: Opinion polls show a growing support of active euthanasia in Germany. The hospice movement rejects active euthanasia and pleads for a qualified care for the dying. The aim of our study was to evaluate how far the work and the ideas of the hospice movement are known in Germany and to which extend this knowledge influences the attitude towards active euthanasia. METHODS: An interview of 200 people in the pedestrian area of Mainz was undertaken. RESULTS: 73% of all interviewees supported active euthanasia. Significant predictors for opposition to active euthanasia were increasing age and belonging to the roman catholic confession. However, 72% of active euthanasia supporters did not know what a hospice is, and 80% were not aware of the existence of such an establishment in Mainz. Opponents of euthanasia had significantly more knowledge of these items. CONCLUSION: The results of our study indicate that physicians should wherever possible explain the aims and the work of the hospice movement who should be their ally in a qualified commitment for the dying. It can be expected that the hospice movement will find a lot of sympathy in the population as 2 of its major aims--openness in communication and dying at home wherever possible--were shared by the vast majority of all interviewees: in case of incurable disease 92% wanted to be informed on their diagnosis, and 84% wanted to die at home or in their families home.