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We describe the surgical reduction of a traumatic, unilateral cervical vertebral facet joint luxation in a large breed dog. Computed tomography (CT) including CT myelography revealed complete luxation of the left articular processes C6 to C7 without fracture of the main weight-bearing structures. There was marked spinal cord compression secondary to the malalignment. Due to the non-ambulatory tetraparetic status, open reduction was chosen as the treatment of choice. After making a dorsal surgical approach to the caudal cervical spine, the luxated articular processes were visible and repositioned. Owing to marked mobility of this joint, temporary stabilization with a nonabsorbable suture between the spinous processes of C6 and C7 was performed and good stability was obtained. The dog recovered uneventfully from the surgery and regained normal ambulation. Follow-up examination including a second CT 9 months after surgery showed no neurological abnormalities and unrestricted motion of the neck. Normal cervical vertebral alignment with moderate osteoarthritis of the right facet joint and mild spondylosis deformans C6 to C7 were present. The present case report shows successful management of a traumatic cervical facet joint luxation without persistent neurological deficits. Open reduction and temporary stabilization with suture material seem to be a valuable method of treatment. The dorsal approach allowed direct inspection of the facet joints with concurrent access to place suture material for temporary stabilization.

BACKGROUND Tyrosine kinase inhibitors (TKIs) have improved the outcome of patients with gastrointestinal stromal tumors (GISTs), but most patients eventually develop resistance and progress. Dasatinib is a potent inhibitor of BCR-ABL, KIT, and SRC family kinases as well as imatinib-resistant cells. In GISTs, response evaluation is routinely done using computed tomography (CT) and 18 F-fluorodeoxyglucose positron emission tomography coupled to CT (FDG-PET/CT) for early response assessment and outcome prediction. METHODS This was a 2-stage, phase 2 trial investigating dasatinib 2 × 70 mg per day in patients with histologically proven, TKI-naive, FDG-PET/CT-positive GIST. The primary endpoint was FDG-PET/CT response. RESULTS Of 52 planned patients, 47 were enrolled from January 2008 to November 2011, when the trial was terminated because of slow accrual. In total, 42 patients were eligible. The median patient age was 61 years, 24 patients were men, and 18 were women. Performance status was 0 in 29 patients and 1 in 13 patients. The median follow-up was 67.2 months. Patients went off trial for elective surgery (n = 8), after 26 cycles as per protocol (n = 5), for disease progression (n = 14), for toxicity (n = 7), and for other reasons (n = 5); and 3 patients died (2 had discontinued drug and 1 was still receiving drug). Toxicity was grade 4 in 5% and grade 3 in 48% of patients and was most often gastrointestinal or pulmonary. Dose was interrupted or reduced in 25% of cycles. The FDG-PET/CT response rate (complete plus partial responses) at 4 weeks was 74% (95% confidence interval, 56%-85%; 14 patients had a complete response, 17 had a partial response, 6 had stable disease, 3 had progressive disease, and 2 were not evaluable). The median progression-free survival was 13.6 months, and the median overall survival was not reached. CONCLUSIONS Dasatinib produced high metabolic response rates in TKI-naive patients with FDG-PET/CT-positive GIST. Cancer 2018;124:1449-54. © 2018 American Cancer Society.

Tyrosine kinase inhibitors (TKIs) have improved the outcome of patients with gastrointestinal stromal tumors (GISTs), but most patients eventually develop resistance and progress. Dasatinib is a potent inhibitor of BCR-ABL, KIT, and SRC family kinases as well as imatinib-resistant cells. In GISTs, response evaluation is routinely done using computed tomography (CT) andThis was a 2-stage, phase 2 trial investigating dasatinib 2 × 70 mg per day in patients with histologically proven, TKI-naïve, FDG-PET/CT-positive GIST. The primary endpoint was FDG-PET/CT response.Of 52 planned patients, 47 were enrolled from January 2008 to November 2011, when the trial was terminated because of slow accrual. In total, 42 patients were eligible. The median patient age was 61 years, 24 patients were men, and 18 were women. Performance status was 0 in 29 patients and 1 in 13 patients. The median follow-up was 67.2 months. Patients went off trial for elective surgery (n = 8), after 26 cycles as per protocol (n = 5), for disease progression (n = 14), for toxicity (n = 7), and for other reasons (n = 5); and 3 patients died (2 had discontinued drug and 1 was still receiving drug). Toxicity was grade 4 in 5% and grade 3 in 48% of patients and was most often gastrointestinal or pulmonary. Dose was interrupted or reduced in 25% of cycles. The FDG-PET/CT response rate (complete plus partial responses) at 4 weeks was 74% (95% confidence interval, 56%-85%; 14 patients had a complete response, 17 had a partial response, 6 had stable disease, 3 had progressive disease, and 2 were not evaluable). The median progression-free survival was 13.6 months, and the median overall survival was not reached.Dasatinib produced high metabolic response rates in TKI-naive patients with FDG-PET/CT-positive GIST. Cancer 2018;124:1449-54. © 2018 American Cancer Society.

IntroductionResearch in palliative care (PC) is often regarded as challenging due to the vulnerability of the population and other peculiarities. We aim to systematically identify barriers to research in PC in the literature.MethodsThe electronic databases CINAHL, MEDLINE were searched for papers published in the last 25 years. Citations and then abstracts were screened for inclusion. Original papers were included on first-level analysis. On a second level reviews, reports, and position papers were analyzed. Papers containing a direct patient report were specifically analyzed. Barriers were categorized (ethical considerations, financial and time expenses, study design and methodology, human resources and politics) and results quantified.ResultsTwenty-one original papers and 65 other papers were included. Five studies involved patients directly, five were systematic reviews, three were study experiences, and seven were surveys or workshop reports. Most papers originated from UK, USA, or Norwegian U...

A practical enantioselective route to chiral 5-phenylbicyclo[2.2.2]oct-5-en-2-one 1 has been designed and developed. The target compound has been obtained as colorless crystals in 22% yield from 2-cyclohexenone, with an enantiomeric ratio higher than 99.5:0.5 and notably high chemical purity (> 99%). Three intermediates out of nine chemical steps are isolated. It is noteworthy that this process is devoid of any chromatography or distillation although all but one intermediate are oils. Key to success was the optimization of an intramolecular aldol reaction of an in situ prepared ketone aldehyde leading to the solid intermediate (1R,4R,4S,6S)-6-hydroxybicyclo[2.2.2]octan-2-one 9a that is isolated in very high chemical and chiral purity. This is an example of an intramolecular crystallization-induced diastereomer transformation (CIDT). The dehydration of this secondary alcohol to 1 required an extensive screen of reaction conditions to secure an excellent purity, essential for crystallization of this low-mel...

SummaryThe influence of the tibial tuberosity conformation on cranial cruciate ligament (CrCl) rupture was evaluated and the size of the tibial tuberosity of healthy dogs (group H) was compared with dogs with CrCl rupture (group R) and dogs treated by tibial tuberosity advancement (TTA) (group T). The medio-lateral radio-graphs of 219 stifle joints were evaluated. Relative tibial tuberosity width (rTTW), proximal tibial tuberosity angle (PTTA), tibial plateau angle (TPA), tibial width (TW) and tibial plateau length (TPL) were measured on each radiograph. Body weight (BW) was measured and relative body weight (rBW) was calculated. The data from group H was compared with that of group R and group T. Group H had significantly larger rTTW, lower BW, lower rBW and smaller PTTA than group R. A comparison of groups H and T showed that dogs from group H were significantly younger, had a lower BW, a lower rBW, a greater PTTA and a smaller rTTW. In each of the comparisons, the TPA and the TW/TPL were not significantly different. The conformation of the canine tibial tuberosity has a significant influence on CrCl rupture. We hypothesized that the smaller the tibial tuberosity width, the larger the cranial tibial thrust, which results in more rapid CrCL degeneration, thus leading to rupture in a younger population of dogs. The rTTW could be a helpful measurement for breeding selection. Only dogs with a rTTW of more than 0.90 should be used for breeding.

Das Tumorlyse-Syndrom ist eine wichtige hamato-onkologische Notfallsituation. Patienten mit einem erhohten Risiko mussen klinisch und laborchemisch engmaschig uberwacht werden. Eine gute Hydrierung ist die wichtigste praventive Massnahme, um ein Tumorlyse-Syndrom zu verhindern.

Le syndrome de lyse tumorale est une importante situation d’urgence hemato-oncologique. Les patients a haut risque doivent etre surveilles de tres pres, cliniquement et en laboratoire. Une bonne hydratation est la plus importante mesure preventive du syndrome de lyse tumorale.

An operationally simple and scalable synthesis of enantiomerically pure bicyclo[2.2.2]octadiene (bod*) ligands relying on an organocatalytic one-pot Michael addition–aldol reaction with cheap 2-cyclohexenone and phenylacetaldehyde is presented. The crystalline bicyclic product 4a (6-hydroxy-5-phenylbicyclo[2.2.2]octan-2-one) is transformed into phenylbicyclo[2.2.2]oct-5-en-2-one 2, a versatile starting material for the 2-step synthesis of both symmetrical, such as Hayashi’s Ph-bod* ligand, as well as novel unsymmetrical chiral dienes.

In an earlier study, intravenous (i.v.) ibandronate 6 mg administered every 3-4 weeks had a similarly good renal safety profile whether infused over 15 or 60 min in women with breast cancer and bone metastases. This current study focuses on the renal safety of the extended use of ibandronate.Patients completing the original study could choose to enter a follow-up phase and continue (or switch) to receive ibandronate 6 mg by 15-min i.v. infusion every 3-4 weeks. The primary endpoint was the percentage of patients with a serum creatinine increase of ≥44.2 mmol/l (= 0.5 mg/dl) from core baseline.Fourteen patients entered the follow-up phase and received a median of 16 infusions (range: 9-24). No patient reached the primary endpoint. Most adverse events were mild to moderate in intensity. None of the 6 reported treatment-related adverse events was considered severe or reported as a serious adverse event.Ibandronate was well tolerated when administered as a 6-mg i.v. infusion over 15 min every 3-4 weeks during the follow-up phase to the earlier core study. No evidence of any treatment-related deterioration in renal function was noted, and no new or unexpected adverse events occurred.

Background. Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC). Patients and Methods. Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression-free survival at 12 weeks (PFS12). Results. Forty-five patients were enrolled. The median age was 63 years; 89% had Child-Pugh class A disease and 47% had distant metastases. PFS12 was rated successful in 15 patients (33%; 95% confidence interval, 20%–47%). Over the whole trial period, one complete response and a 40% rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related. Conclusion. Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (>13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374).

SummaryThis report describes the successful use of the novel fixed-angle locking plating system ALPS (advanced locking plate system) in the case of dorsal tarsometatarsal instability in a cat. Partial arthrodesis of the tarsometatarsal joint was performed with a two hole ALPS 5 and two 2.4 mm selftapping locking screws through a small dorsal approach. Five days after the surgery the cat was walking without lameness. Radiographs made after six weeks showed uneventful healing. ALPS offers an alternative to existing plating systems when selecting an implant for the stabilisation of dorsal tarsometatarsal instabilities in cats.

Background: In an earlier study, intravenous (i.v.) ibandronate 6 mg administered every 3–4 weeks had a similarly good renal safety profile whether infused over 15 or 60 min in wome