Reference intervals for various measurements of canine left atrial size and function obtained using two-dimensional and three-dimensional echocardiography.

BACKGROUND: Many canine cardiac diseases are associated with left atrial (LA) remodeling and decreased function. For accurate assessment of LA indices, large-scale and prospectively determined reference intervals are necessary. OBJECTIVES: To generate reference intervals of LA size and function using two-dimensional and three-dimensional echocardiography. ANIMALS: Two hundred and one healthy adult dogs. METHODS: Left atrial volume was assessed in right parasternal long-axis, left apical four-chamber and two-chamber views using monoplane Simpson's method, two-dimensional and three-dimensional speckle tracking. Additionally, LA diameter was measured in right parasternal short-axis and long-axis views. Furthermore, LA function was determined by measuring strain and calculating LA fractional shortening and ejection fraction. All variables were tested for correlation to heart rate, age, and body weight. For LA diameter and volume, scaling exponents and prediction intervals were generated using allometric scaling. Reference intervals for LA function parameters were calculated using nonparametric methods. RESULTS: Left atrial diameter and volume showed a strong correlation with body weight. The scaling exponent for LA diameter was approximately 1/3 (0.34-0.40) and approximately one for volume measurements (0.97-1.26). Parameters of LA function showed no clinically relevant correlation with body weight, except for two variables, which showed a mild negative correlation. No clinically relevant correlations with age or heart rate were found. CONCLUSIONS: Reference intervals for linear, two-dimensional and three-dimensional measurements of LA size and function were established. The wide range of measurement methods offers the opportunity to select the appropriate reference values for LA evaluation depending on the available technical possibilities.

Neurocognitive functioning in patients with first-episode schizophrenia: results of a prospective 15-year follow-up study.

To evaluate the course of neuropsychological impairment, patients with first-episode schizophrenia and healthy controls were assessed with a comprehensive test battery at the time of index treatment and after a 5- and 15-year follow-up period. Summary scores for verbal intelligence (VBI), spatial organization, verbal fluency, verbal learning, semantic memory, visual memory, delay/retention rate, short-term memory, visual-motor processing and attention (VSM) and abstraction/flexibility were constructed. Our results show that neurocognitive functioning is impaired already at the onset of schizophrenia and remains stable over the 15-year follow-up period with an improvement in VBI. With regard to the presence of a deficit syndrome, it became apparent that the group with a deficit syndrome showed a deterioration of neurocognitive functions during the follow-up period, most pronounced in VSM. On the other hand, the group without a deficit syndrome showed an improvement in neurocognitive functions at the 15-year follow-up, which exceeded the learning effects of healthy control subjects. Neurocognitive performance at index assessment strongly predicted the performance at the 15-year follow-up. Most likely due to the small sample size, there were only weak associations between treatment with different types of neuroleptics and neurocognitive performance.

[Cost analysis as a tool for assessing the efficacy of intensive care units]. / Kosten als Instrument zur Effizienzbeurteilung intensivmedizinischer Funktionseinheiten.

BACKGROUND: The German "Hospital Structure Act" intends to align the state hospital planning on quality criteria. Within this process cost-utility analyses (CUAs) shall be used to assess the efficacy of medical care. To be objective, CUAs of intensive care units (ICUs) require standardization (adjustment) of costs. The present study analyzed the extent to which treatment costs are related to patient-specific baseline variables (such as type and severity of the primary disease). METHODS: From 2000-2004, a bottom-up procedure was used to quantify total costs on 14 ICUs in nine German university hospitals. Results were combined with demographic data, and data indicating type (ICD-10 codes) and severity (ICU scoring systems) of the primary disease at ICU admission. Various statistical models were tested to identify that which best described the associations between baseline variables and costs. RESULTS: In all, 3803 critically ill patients could be examined. The median of treatment costs per patient was 3199 € (IQR 1768-6659 €). No model allowed an acceptably precise adjustment of costs; the estimated mean absolute prognostic error was at least 3860 € (mean relative prognostic error 66%), when we tested an Extreme Gradient Boosting Model. CONCLUSION: Instruments which are currently available (cost adjustment based on patient-specific baseline variables) do not allow a standardization of costs, and an objective CUA of ICUs. Factors unknown at baseline may cause a large portion of treatment costs.

Predictors of Sudden Cardiac Death in Doberman Pinschers with Dilated Cardiomyopathy.

BACKGROUND: Doberman Pinschers with dilated cardiomyopathy (DCM) are at high risk of sudden cardiac death (SCD). Risk factors for SCD are poorly defined. AIM: To assess cardiac biomarkers, Holter-ECG, echocardiographic variables and canine characteristics in a group of Doberman Pinschers with DCM dying of SCD and in a DCM control group to identify factors predicting SCD. METHODS/ANIMALS: A longitudinal prospective study was performed in 95 Doberman Pinschers with DCM. Forty-one dogs died within 3 months after the last cardiac examination (SCD-group) and were compared to 54 Doberman Pinschers with DCM surviving 1 year after inclusion. Holter-ECG, echocardiography, measurement of N-terminal prohormone of brain-natriuretic peptide (NT-proBNP), and cardiac Troponin I (cTnI) concentrations were recorded for all dogs. RESULTS: Volume overload of the left ventricle (left ventricular end-diastolic volume (LVEDV/BSA) > 91.3 mL/m²) was the single best variable to predict SCD. The probability of SCD increases 8.5-fold (CI0.95  = 0.8-35.3) for every 50 mL/m²-unit increment in LVEDV/BSA. Ejection fraction (EF), left ventricular end-systolic volume (LVESV/BSA) and NT-proBNP were highly correlated with LVEDV/BSA (r = -0.63, 0.96, 0.86, respectively). Generated conditional inference trees (CTREEs) revealed that the presence of ventricular tachycardia (VT), increased concentration of cTnI, and the fastest rate (FR) of ventricular premature complexes (VPC) ≥260 beats per minute (bpm) are additional important variables to predict SCD. CONCLUSION: Conditional inference trees provided in this study might be useful for risk assessment of SCD in Doberman Pinschers with DCM.

Inflammatory role and prognostic value of platelet chemokines in acute coronary syndrome.

Activated platelets and neutrophils exacerbate atherosclerosis. Platelets release the chemokines CXCL4, CXCL4L1 and CCL5, whereas myeloperoxidase (MPO) and azurocidin are neutrophil-derived. We investigated whether plasma levels of these platelet and neutrophil mediators are affected by the acute coronary syndrome (ACS), its medical treatment, concomitant clinical or laboratory parameters, and predictive for the progression of coronary artery disease (CAD). In an observational study, the association of various factors with plasma concentrations of platelet chemokines and neutrophil mediators in 204 patients, either upon admission with ACS and 6 hours later or without ACS or CAD, was determined by multiple linear regression. Mediator release was further analysed after activation of blood with ACS-associated triggers such as plaque material. CXCL4, CXCL4L1, CCL5, MPO and azurocidin levels were elevated in ACS. CXCL4 and CCL5 but not CXCL4L1 or MPO were associated with platelet counts and CRP. CXCL4 (in association with heparin treatment) and MPO declined over 6 hours during ACS. Elevated CCL5 was associated with a progression of CAD. Incubating blood with plaque material, PAR1 and PAR4 activation induced a marked release of CXCL4 and CCL5, whereas CXCL4L1 and MPO were hardly or not altered. Platelet chemokines and neutrophil products are concomitantly elevated in ACS and differentially modulated by heparin treatment. CCL5 levels during ACS predict a progression of preexisting CAD. Platelet-derived products appear to dominate the inflammatory response during ACS, adding to the emerging evidence that ACS per se may promote vascular inflammation.

Predictors of clinical effectiveness of Hymenoptera venom immunotherapy.

BACKGROUND: Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors, of which the relative importance is unknown. OBJECTIVE: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC), mastocytosis in the skin (MIS) and of other parameters with the frequency of objective systemic reactions during in-hospital sting challenge (SC). METHODS: In this observational retrospective study, we enrolled 1532 patients (1609 cases due to double SC) with established honeybee or vespid venom allergy who had undergone VIT and a subsequent SC. Data were collected on various putative risk factors. Adult-onset MIS and/or a BTC > 20.0 µg/L was defined as clinical indicators of systemic mastocytosis. Relative rates were calculated with logistic regression models. RESULTS: Ninety-eight patients (6.4%) presented with MIS and/or BTC > 20.0 µg/L. 104 cases (6.5%) developed objective generalized symptoms during SC. In the absence of MIS, a BTC ≤ 20 µg/L did not increase the risk for VIT failure. The most important factors associated with a worse outcome were ACE inhibitor medication (OR 5.24, 95% CI 1.83-13.00, P < 0.001), honeybee venom allergy (OR 5.09, 95% CI 3.17-8.15, P < 0.001), systemic allergic reaction during VIT (OR 3.07, 95% CI 1.79-5.14, P < 0.001), and a substantial likelihood to suffer from SM (OR 2.74, 95% CI 1.37-5.22, P = 0.003), whereas a double VIT (OR 0.51, 95% CI 0.27-0.90, P = 0.027) and a longer duration of therapy (OR 0.68 per treatment month, 95% CI 0.50-0.93, P = 0.017) reduced the failure rate. CONCLUSION: The magnitude of therapeutic success correlates with type of venom, duration of therapy, and venom dose. Adult-onset MIS and/or a BTC > 20 µg/L is a significant, albeit not the strongest determinant for VIT failure. According to its odds ratio, ACE inhibitor therapy appears to be associated with the highest risk for VIT failure.

Effects of continuous milking during a field trial on productivity, milk protein yield and health in dairy cows.

The objective of this field study with an automatic milking system was to evaluate the effects of omitting the dry period on health and productivity during the subsequent lactation in dairy cows. A total of 98 German Simmental cows of six Southern German farms were assigned randomly to two experimental groups: The first group was dried-off 56 days before calving (D for dried-off, n=49), and the second group was milked continuously during this period until calving (CM for continuous milking, n=49). From the latter a third group emerged, including cows that dried-off themselves spontaneously (DS for dried-off spontaneously, n=14). Blood serum values of glucose, ß-hydroxybutyrate (BHBA), non-esterified fatty acids (NEFA) and IGF-1 showed most pronounced fluctuations in D cows. Over the entire study period, the concentrations of BHBA and NEFA were markedly lower in the CM and DS groups. Furthermore, IGF-1 concentration was lowest for D cows and also decrease in back fat thickness was more pronounced. Mean concentration of milk protein was markedly higher in CM and DS cows (3.70% and 3.71%) compared with D cows (3.38%). Owing to the lower 305-day milk yield (-15.6%) and the lower total milk yield (-3.1%), the total amount of produced protein in the subsequent lactation was 2.5% (6.8 kg) lower, although the additional protein amount in CM cows from week -8 to calving was 35.7 kg. The greatest benefit resulted from positive effects on fertility and the lower incidence of diseases: CM cows had their first oestrus 1 week earlier compared with D cows, they also conceived earlier and showed a significantly lower risk of developing hypocalcaemia, ketosis and puerperal disorders. The present study showed that the costs of medical treatment and milk losses were twice as high in D cows, compared with CM and DS cows, and thus the reduced costs because of the more stable health outweighed the financial losses of milk yield by +18.49 € per cow and lactation.

Existential behavioural therapy for informal caregivers of palliative patients: a randomised controlled trial.

BACKGROUND: Existential behavioural therapy (EBT) was developed to support informal caregivers of palliative patients in the last stage of life and during bereavement as a manualised group psychotherapy comprising six sessions. We tested the effectiveness of EBT on mental stress and quality of life (QOL). METHODS: Informal caregivers were randomly assigned (1:1) to EBT or a treatment-as-usual control group using computer-generated numbers in blocks of 10. Primary outcomes were assessed with the Brief Symptom Inventory (subscales somatisation, anxiety and depression), the Satisfaction with Life Scale (SWLS), the WHOQOL-BREF and a numeric rating scale for QOL (QOL-NRS, range 0-10). Data were collected at baseline, pre-treatment, post-treatment and follow-ups after 3 and 12 months. Treatment effects were assessed with a multivariate analysis of covariance. RESULTS: Out of 160 relatives, 81 were assigned to EBT and 79 to the control group. Participants were 54.5 ± 13.2 years old; 69.9% were female. The multivariate model was significant for the pre-/post-comparison (p=0.005) and the pre-/12-month comparison (p=0.05) but not for the pre-/3-month comparison. Medium to large effects on anxiety and QOL (SWLS, WHOQOL-BREF, QOL-NRS) were found at post-treatment; medium effects on depression and QOL (QOL-NRS) emerged in the 12-month follow-up. No adverse effects of the intervention were observed. CONCLUSION: Existential behavioural therapy appears to exert beneficial effects on distress and QOL of informal caregivers of palliative patients. Further longitudinal evidence is needed to confirm these findings.

[Behaviour therapy in the practice management of a veterinary practice. Survey among practicing veterinarians and veterinarians specializing in behaviour therapy]. / Verhaltenstherapie im Praxismanagement einer Tierarztpraxis. Befragung praktischer und auf Verhaltenstherapie spezialisierter Tierärzte.

OBJECTIVE: of the study was to investigate whether behaviour therapy may be an economic niche within practice management. MATERIAL AND METHODS: A questionnaire was used to analyze to what extent veterinarians have already applied behaviour therapy (BT) and how they evaluate economic efficiency and patient owners' attitude. The descriptive analysis included the data from 312 practicing veterinarians (167 randomly selected, interviewed and 145 signed on for training sessions, veterinarians) and of 23 veterinarians specialized in BT. RESULTS: Two-thirds (67% of n=288) of the practicing veterinarians offered BT in their practices. The economic efficiency of BT was evaluated as positive by 64% (of n=281) of the practicing veterinarians and by 83% (of n=23) of specialists. 32% (of n = 146) of practitioners who offered behavioural therapy confirmed an increase in sales through the application of BT. Among the specialists, 84% (of n=19) confirmed this experience. In comparison to the specialists and literature data, most of the practicing veterinarians spent insufficient time (61% of n=180) for a behaviour consultation. Furthermore, most of them (86% of n=162) charged less for BT than the amounts fixed by the German Payment Regulations (Gebührenordnung für Tierärzte), as compared to the specialists. CONCLUSION: The specialized veterinarians offered, in contrast to most practitioners, a consultation of BT with sufficiently calculated time and accurate payment planning to realise a therapeutic and commercial outcome. Therefore, the assessment of the economic efficiency of BT and their sales increase through BT were better than the estimation of the practicing veterinarians. Behaviour therapy cannot be managed by providing advice free of charge or charging less. Veterinarians have to become aware that BT is a veterinary area of specialization for which an adequate qualification is necessary. If the veterinarian is not specialized in BT he should refer to a qualified colleague.

Nutritional screening for risk prediction in patients scheduled for abdominal operations.

BACKGROUND: Increased risks related to surgery might reflect the nutritional status of some patients. Such a group might benefit from perioperative nutritional support. The purpose of this study was to identify the relative importance of nutritional risk screening along with established medical, anaesthetic and surgical predictors of postoperative morbidity and mortality. METHODS: This prospective observational study enrolled consecutive eligible patients scheduled for elective abdominal operations. Data were collected on nutritional variables (body mass index, weight loss, food intake), age, sex, type and extent of operation, underlying disease, American Society of Anesthesiologists grade and co-morbidities. A modified composite nutritional screening tool (Nutritional Risk Screening, NRS 2002) currently recommended by European guidelines was used. Relative complication rates were calculated with multiple logistic regression and cumulative proportional odds models. RESULTS: Some 653 patients were enrolled of whom 132 (20.2 per cent) sustained one or more postoperative complications. The frequency of this event increased significantly with a lower food intake before hospital admission. No other individual or composite nutritional variable provided comparable or better risk prediction (including NRS 2002). Other factors significantly associated with severe postoperative complications were ASA grade, male sex, underlying disease, extent of surgical procedure and volume of transfused red cell concentrates. CONCLUSION: In abdominal surgery, preoperative investigation of feeding habits may be sufficient to identify patients at increased risk of complications. Nutritional risk alone, however, is not sufficient to predict individual risk of complications reliably.

Mortality due to myocardial infarction in the Bavarian population during World Cup Soccer 2006.

BACKGROUND: Previously, we had demonstrated that the World Cup Soccer 2006 provoked levels of emotional stress sufficient to increase the incidence of acute cardiovascular events. We sought to assess whether mortality was also increased as a result. METHOD: We analyzed daily data on mortality due to myocardial infarction (MI) and total mortality using data from the Bavarian State Office for Statistics. We retrospectively assessed study periods from 2006, 2005 and 2003. Quasi-Poisson regression with a log link to model the number of daily deaths was used. To be able to account for a possible delay, we also fitted a cubic distributed lag quasi-Poisson model for both 1 and 2 weeks post-exposure. RESULTS: A total of 6,699 deaths due to MI were investigated. No increase in death was found on days of World Cup matches either with or without German participation compared to the matched control periods. In addition, none of the analyses showed a significant effect of the (lagged) exposure to the risk period. Likewise, total mortality rates remained unchanged over the entire period of our analysis. CONCLUSION: During World Cup Soccer, the number of deaths due to myocardial infarction was not measurably increased compared to a matched control period. Thus, we could not demonstrate a translation of a stress-induced increase of cardiac morbidity into a noticeable increase in mortality. However, our findings are based on a public mortality registry, which may be flawed in many ways, regarding ascertainment of causes of death, in particular.

Association of A31P and A74T polymorphisms in the myosin binding protein C3 gene and hypertrophic cardiomyopathy in Maine Coon and other breed cats.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an inherited autosomal dominant trait in cats. The A31P single nucleotide polymorphism (SNP) in the myosin binding protein C 3 gene is thought to be the causative mutation in Maine Coon cats. Additionally, the A74T SNP is offered as a genetic test for HCM. OBJECTIVES: To evaluate the genetic association between the above-mentioned SNPs and phenotypes. ANIMALS: Eighty-three Maine Coon cats and 68 cats of other breeds. METHODS: The study was performed prospectively. Cats were phenotyped as healthy or HCM with echocardiography. Taqman genotyping assays were used for genotyping; results were confirmed by sequencing analysis. RESULTS: A31P was found in 18/83 (22%) Maine Coon cats. Fifteen of 18 Maine Coons (83%) with the A31P mutation were healthy on echocardiographic examination (mean age 65 months). A74T was present in 28/79 (35%) of Maine Coons and in 42/68 (62%) of other cat breeds. Twenty-two of 28 (79%) of Maine Coons and 21/42 (62%) of other breed cats with the A74T mutation were healthy at a mean age of 72 months and 91 months, respectively. Of 12 Maine Coons with HCM, 9 (75%) were genotype-negative for A31P and 6 (50%) for A74T. Allele frequencies did not differ significantly (P= .47) between phenotype groups. None of the evaluated genetic tests was able to provide useful predictive information of disease outcome. CONCLUSIONS AND CLINICAL IMPORTANCE: The value of currently available genetic tests is low in the cats of this study. The mutations analyzed appear to have a low penetrance, and even homozygote cats can remain healthy.

Correction for covariate measurement error in nonparametric longitudinal regression.

We introduce a correction for covariate measurement error in nonparametric regression applied to longitudinal binary data arising from a study on human sleep. The data have been surveyed to investigate the association of some hormonal levels and the probability of being asleep. The hormonal effect is modeled flexibly while we account for the error-prone measurement of its concentration in the blood and the longitudinal character of the data. We present a fully Bayesian treatment utilizing Markov chain Monte Carlo inference techniques, and also introduce block updating to improve sampling and computational performance in the binary case. Our model is partly inspired by the relevance vector machine with radial basis functions, where usually very few basis functions are automatically selected for fitting the data. In the proposed approach, we implement such data-driven complexity regulation by adopting the idea of Bayesian model averaging. Besides the general theory and the detailed sampling scheme, we also provide a simulation study for the Gaussian and the binary cases by comparing our method to the naive analysis ignoring measurement error. The results demonstrate a clear gain when using the proposed correction method, particularly for the Gaussian case with medium and large measurement error variances, even if the covariate model is misspecified.

Serum concentration of baseline mast cell tryptase: evidence for a decline during long-term immunotherapy for Hymenoptera venom allergy.

BACKGROUND: Baseline serum mast cell tryptase concentration (BTC) is thought to reflect the constitutive mast cell load or activity of an individual patient. Little is known about the individual stability of BTC during long-term venom immunotherapy (VIT). OBJECTIVE: To investigate the intra-individual stability of BTC over time in patients with Hymenoptera venom allergy. METHODS: Three hundred and two patients were studied. BTC was measured before and at least twice during VIT. At least 4 weeks lay between BTC measurements and the most recent field sting, in-hospital sting, or preceding venom injection. Multifactorial mixed linear models were used to analyse BTC changes over time. RESULTS: Median observation time was 4.2 years (range 2-12 years). Before VIT, the median BTC was 6.8 microg/L (range 1.14-177 microg/L). The median coefficient of variation (CV) over time was 15.3% (range 1.9-63.8%). The median CV was significantly smaller in patients presenting with an elevated BTC (>11.4 microg/L) than in patients with a normal BTC (11.4%, range 2.6-39.5%; vs. 17.6%, range 1.9- 63.8%; P<0.001). During VIT and after adjusting for age and gender, we found a slight but significant decrease of BTC over time (2.5% per year, 95% confidence interval 2.0-3.0%, P<0.001). CONCLUSION: Individual variation of BTC during VIT does not rise when BTC is increased before therapy. VIT is associated with a small, but continuous decrease of BTC over time possibly indicating a dampened mast cell function or a decline in mast cell burden.

Phenotypic and genotypic bacterial antimicrobial resistance in liquid pig manure is variously associated with contents of tetracyclines and sulfonamides.

AIMS: Antibiotic residues as well as antibiotic-resistant bacteria in environmental samples might pose a risk to human health. This study aimed to investigate the association between antibiotic residues and bacterial antimicrobial resistance in liquid pig manure used as fertilizer. METHODS AND RESULTS: Concentrations of tetracyclines (TETs) and sulfonamides (SULs) were determined by liquid chromatography-mass spectrometry in 305 pig manure samples; antibiotic contents were correlated to the phenotypic resistance of Escherichia coli (n = 613) and enterococci (n = 564) towards up to 24 antibiotics. In 121 samples, the concentration of the TET resistance genes tet(M), tet(O) and tet(B) was quantified by real-time-PCR. TETs were found in 54% of the samples. The median sum concentration of all investigated TETs in the positive samples was 0.73 mg kg(-1). SULs were found with a similar frequency (51%) and a median sum concentration of 0.15 mg kg(-1) in the positive samples. Associated with the detection of TETs and/or SULs, resistance rates were significantly elevated for several substances - some of them not used in farm animals, e.g. chloramphenicol and synercid. In addition, multiresistant isolates were found more often in samples containing antibiotics. Analysis of the resistance genes tet(M) and tet(O) already showed a significant increase in their concentrations - but not in tet(B) - in the lowest range of total TET concentration. Mean tet(M) concentrations increased by the factor of 4.5 in the TET concentration range of 0.1-1 mg kg(-1), compared to negative manure samples. CONCLUSIONS: Antibiotic contamination of manure seems to be associated with a variety of changes in bacterial resistance, calling for a prudent use of antibiotics in farm animals. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides an interdisciplinary approach to assess antimicrobial resistance by combining the microbiological analysis of bacterial resistance with high quality chemical analysis of antibiotic residues in a representative number of environmental samples.

Retrospective study of 871 dogs with thrombocytopenia.

Eight hundred and seventy-one dogs with thrombocytopenia were divided into the following five categories: immune-mediated thrombocytopenia (49; 5.6 per cent), thrombocytopenia caused by disseminated intravascular coagulation (DIC) (52; 6.0 per cent), thrombocytopenia caused by miscellaneous disorders (222; 25.5 per cent), neoplasia-associated thrombocytopenia (244; 28 per cent) and inflammatory/infectious thrombocytopenia (304; 34.9 per cent). The incidence of thrombocytopenia among the hospital population was 6.7 per cent. The dogs with immune-mediated thrombocytopenia and thrombocytopenia caused by DIC had significantly (P<0.001) lower platelet counts (median 32.0 x 10(9)/l and 55.0 x 10(9)/l, respectively) than the dogs in the other three categories.

Analysis of cerebrospinal fluid in healthy rabbits and rabbits with clinically suspected encephalitozoonosis.

Samples of uncontaminated cerebrospinal fluid (csf) were collected from the cisterna magna of 20 healthy laboratory rabbits and 21 pet rabbits with vestibular disease and/or paresis due to clinically suspected encephalitozoonosis. In the healthy rabbits' csf the leucocyte count was

Intra-tumoral gene delivery of feIL-2, feIFN-gamma and feGM-CSF using magnetofection as a neoadjuvant treatment option for feline fibrosarcomas: a phase-I study.

Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have a high relapse rate. In this study, a new treatment option based on immune stimulation by intra-tumoral delivery of three feline cytokine genes was performed. The objective of this phase-I dose-escalation study was to determine a safe dose for further evaluation in a subsequent phase-II trial. Twenty-five client-owned cats with clinical diagnosis of fibrosarcoma - primary tumours as well as recurrences - entered the study. Four increasing doses of plasmids coding for feIL-2, feIFN-gamma or feGM-CSF, respectively, were previously defined. In groups I, II, III and IV these doses were 15, 50, 150 and 450 microg per plasmid and a corresponding amount of magnetic nanoparticles. Two preoperative intra-tumoral injections of the magnetic DNA solution were followed by magnetofection. A group of four control cats received only surgical treatment. Side effects were registered and graded according to the VCOG-CTCAE scale and correlated to treatment. Statistical analyses included one-way anova, post hoc and Kruskal-Wallis tests. ELISA tests detecting plasma feIFN-gamma and plasma feGM-CSF were performed. One cat out of group IV (450 microg per plasmid) showed adverse events probably related to gene delivery. As these side effects were self-limiting and occurred only in one of eight cats in group IV, this dose was determined to be well tolerable. Altogether six cats developed local recurrences during a 1-year observation period. Four of these cats had been treated with dose IV. Regarding these observations, a subsequent phase-II trial including a representative amount of cats should be tested for the efficacy of dose IV as well as dose III.

Secular trends in severe renal failure associated with the use of new antimicrobial agents in critically ill surgical patients.

Randomized controlled trials conducted since 2000 have shown that new antibacterial and antifungal agents may reduce the frequency of kidney injury in selected groups of critically ill patients, yet it is unclear whether these benefits translate to the clinical setting. The aim of the present study was to evaluate longitudinally the successive routine implementation of new antimicrobial agents (caspofungin, voriconazole, linezolid) after February 2002 and the association of these agents with the frequency of mechanical renal replacement therapy in postsurgical critically ill patients at risk of severe kidney failure. A retrospective, observational cohort study was performed using data collected prospectively from 1 March 1993 through 28 February 2005. A cohort of 2,123 consecutive cases who required intensive care therapy for more than 2 days was analysed. A statistically significant decrease in the frequency of renal replacement therapy was observed in the later years of the study. After adjustment for relevant covariates, treatment with new antimicrobial agents after February 2002 was identified as an independent factor linked with a reduced risk of severe kidney failure (odds ratio 0.244; 95% confidence interval 0.136-0.439). Thus, the implementation of new antimicrobial agents with reduced or no nephrotoxicity into routine care of critically ill surgical patients is associated with a reduced need for renal replacement therapy.

[Significance of multiple organ failure for the prognosis of surgical intensive care patients]. / Bedeutung des Mehrfachorganversagens für die Prognose des chirurgischen Intensivpatienten.

BACKGROUND: The association of multiple organ failure and acute prognosis is an established fact in intensive care medicine. However, it is unclear whether the number of failing organs is an independent determinant of acute mortality, and whether there are additional effects on long-term outcome. METHODS: We performed a retrospective, observational cohort study using prospectively collected data from March 1993, through February 2005. Three different cohorts were analysed: patients with a short-term intensive care unit (ICU) stay (group I, ICU length of stay > 4 days), with a long-term ICU stay (group II, ICU length of stay > 28 days), and all patients requiring renal replacement therapy during ICU stay (group III). Organ failure was defined according to a modified Goris score. An independent effect of the number of failing organs on patient prognosis was evaluated after adjusting for more than 15 covariables. Acute prognosis was analysed in group I, whereas long-term prognosis was studied in groups II and III. RESULTS: The maximum number of failing organs was an independent determinant of acute prognosis in patients of group I, and of long-term prognosis in groups II and III. CONCLUSION: The effect of multiple organ failure on long-term prognosis emphasizes the importance of this variable for patient outcome. Therefore, multiple organ failure must be part of all therapeutic concepts in critical care. Within those, preventive measures are definitively preferable to keep the number of failing organs as small as possible.