Dagmar S. Trachsel

Patients with inoperable pancreatic cancer have a dismal prognosis with a mean life expectancy of 3-6 months. New treatment modalities are thus urgently needed. Telomerase is expressed in 85-90% of pancreas cancer, and immunogenic telomerase peptides have been characterised. A phase I/II study was conducted to investigate the safety, tolerability, and immunogenecity of telomerase peptide vaccination. Survival of the patients was also recorded. Forty-eight patients with non-resectable pancreatic cancer received intradermal injections of the telomerase peptide GV1001 at three dose levels, in combination with granulocyte-macrophage colony-stimulating factor. The treatment period was 10 weeks. Monthly booster vaccinations were offered as follow-up treatment. Immune responses were measured as delayed-type hypersensitivity skin reaction and in vitro T-cell proliferation. GV1001 was well tolerated. Immune responses were observed in 24 of 38 evaluable patients, with the highest ratio (75%) in the intermediate dose group. Twenty-seven evaluable patients completed the study. Median survival for the intermediate dose-group was 8.6 months, significantly longer for the low- (P = 0.006) and high-dose groups (P = 0.05). One-year survival for the evaluable patients in the intermediate dose group was 25%. The results demonstrate that GV1001 is immunogenic and safe to use. The survival data indicate that induction of an immune response is correlated with prolonged survival, and the vaccine may offer a new treatment option for pancreatic cancer patients, encouraging further clinical studies.

Summary Reasons for performing the study: Admission L‐lactate concentration is a useful and commonly measured biomarker not previously prospectively evaluated in a large multicentre study of critically ill neonatal foals. Objectives: To evaluate overall outcome and the association of survival and L‐lactate concentration at admission ([LAC] ADMIT ) by periparturient history, presenting complaint and clinicians' major diagnosis for ill neonatal foals. Methods: Thirteen university and private equine referral hospitals enrolled 643 foals over the 2008 foaling season. Case details, historical, clinical and clinicopathological data were entered into standardised spreadsheets then unified for analysis. Results: Overall survival was 79% (505/643). Risk of nonsurvival increased with each 1 mmol/l increase in [LAC] ADMIT (odds ratio 1.14, P<0.001). Mean arterial pressure had a small (r 2 = 19.1) but significant (P<0.001) association with [LAC] ADMIT . Foals experiencing known dystocia or premature placental separation had increased [LAC] ADMIT (P<0.001). Single umbilical problems (excluding uroperitoneum), meconium impaction only and failure of passive transfer of immunity only had 100% survival. Six clinicians' major diagnoses had increased odds of nonsurvival for each 1 mmol/l increase in [LAC] ADMIT : ‘sepsis’; ‘unspecified enterocolitis’; ‘unspecified colic’; ‘unspecified trauma’; ‘immune related (not failure of passive transfer of immunity)’ and ‘respiratory only’. Conclusions and potential relevance: Survival of critically ill foals is good but varies with peripartum history, presenting complaint and clinicians' major diagnosis. L‐lactate concentration at admission proves its utility as a valuable prognostic biomarker in neonatal foals and its utility appears to vary with peripartum history and clinicians' major diagnosis.

REASONS FOR PERFORMING STUDY: Standardised exercise tests are used for fitness evaluation of sports horses. Standards are described for Thoroughbreds and Standardbreds; however, limited information is available for Warmbloods. OBJECTIVES: To establish normative standards of performance parameters and heart rate recovery (HRR) in Warmblood riding horses of different levels of fitness using a submaximal incremental exercise test (SIET) performed on a treadmill. METHODS: A SIET was carried out with 29 healthy and treadmill-accustomed Warmbloods: eleven 3-day event horses (TDE) and 18 horses from the National Equestrian Centre (NEC) competing in amateur jumping and/or dressage events. After a warm-up phase, horses performed 2 stages at trot and 3-5 stages at gallop at 6% incline. The first stage lasted 120 s, all others 90 s. Velocity (V) and heart rate (HR) were measured continuously and blood lactate concentration (LAC) at the end of each exercise stage. V at HR 150 and 200 beats/min (V(150), V(200)), V and HR at 2 and 4 mmol/l LAC (V(2), V(4) and HR(2), HR(4), respectively) were calculated and compared between discipline groups. For reference values, horses were divided on the basis of the V(4) -results in good (GP) and average performers (AP) (performance groups). Five minute passive HRR was compared between performance groups. Fifteen NEC horses were retested within 1-3 months. Groups were compared with t tests and P < 0.05 considered significant. RESULTS: Three-day event horses had higher V(150), V(2) and V(4) values than NEC. GP had higher values in all performance parameters compared to AP. No differences were found between test and retest. GP mean recovery HR was different from that of AP from 120 s of recovery onwards. CONCLUSION: Treadmill SIETs are suitable to objectify aerobic capacity in Warmblood riding horses. Normative standards were assessed for well and averagely-trained horses. The results can be referred to when diagnosing patients with exercise intolerance.

Analysis of the heart rate variability (HRV) gains more and more importance in the assessment of training practice and welfare in equine industry. It relies on mathematical analyses of reliably and accurately measured variations in successive inter-beat intervals, measured as RR intervals. Nowadays, the RR intervals can be obtained through two different techniques: a heart rate meter (HRM) or an electrocardiogram (ECG). The agreement and reliability of these devices has not been fully assessed, especially for recordings during exercise. The purpose of this study was to assess the agreement of two commercially available devices using the two mentioned techniques (HRM vs ECG) for HRV analysis during a standardized exercise test. Simultaneous recordings obtained during light exercise and during canter with both devices were available for 36 horses. Data were compared using a Bland-Altman analysis and the Lin's coefficient. The agreement between the assessed HRV measures from the data obtained from the ECG and HRM was acceptable only for the mean RR interval and the mean heart rate. For the other studied measures (SDNN, root mean square of successive differences, SD1, SD2, low frequency, high frequency), the agreement between the devices was too poor for them to be considered as interchangeable in these recording conditions. The agreement tended also to be worse when speed of the exercise increased. Therefore, it is necessary to be careful when interpreting and comparing results of HRV analysis during exercise, as the results will depend upon recording devices. Furthermore, corrections and data processing included in the software of the devices affect largely the output used in the subsequent HRV analysis; this must be considered in the choice of the device.