Calicophoron daubneyi (Paramphistomidae) in deer of the Sumava National Park, Czech Republic - Consequence of prevalent rumen fluke infection in cattle.

A substantial parallel increase in prevalence and geographical spread of the rumen fluke, Calicophoron daubneyi, in livestock in western and central Europe has been recognized in the recent past. In the course of the examination of rectum feces of 471 red deer (Cervus elaphus) and one sika deer (Cervus nippon) from the Fascioloides magna endemic Sumava National Park in the years 2021 and 2022, rumen fluke eggs were detected in four red deer (0.8%) and the sika deer and identified as eggs of C. daubneyi by molecular analysis. Subsequent examination of rectal fecal samples of 247 beef cattle from 22 herds of 14 farms located in or nearby the national park revealed rumen fluke eggs in 53 samples (21.5%) originating from 16 herds of 11 farms, molecularly identified as C. daubneyi eggs as well. One C. daubneyi egg positive red deer and three C. daubneyi egg positive cattle samples also contained fasciolid eggs, respectively, which were detected in 9.5% or 3.6% of the total samples from red deer or cattle, respectively. Results of this investigation reveal the first finding of C. daubneyi in sika deer worldwide and in red deer in mainland Europe and add to the growing number of reports on C. daubneyi in livestock in Europe. Considering that the ratio of cattle excreting rumen fluke eggs exceeded that of deer substantially, it can reasonably be assumed that the C. daubneyi infections in deer are a consequence of the prevalent infection in cattle, illustrating a pathogen spillover event from livestock into wildlife.

Protostrongylus caprae Zdzitowiecki et Boev, 1971 (Nematoda: Protostrongylidae) - First record in Alpine ibex (Capra ibex Linnaeus, 1758) from Europe.

In the course of a survey of the endoparasites of Alpine ibex (Capra ibex) from Austria, examination of the lungs revealed male Protostrongylus nematodes presenting morphological characters which differed from those of the three Protostrongylus species previously reported from this host. Fragments of 16 adult male and 4 adult female nematodes extracted from the lung tissue of two female ibex following peptic digestion were subjected to close microscopic examination. Based on their morphology, the lungworms were identified as Protostrongylus caprae Zdzitowiecki et Boev, 1971. This species was originally described from Siberian ibex (Capra sibirica) in Asia and previously only reported from this host from Kazakhstan and Mongolia. The identification of P. caprae in Alpine ibex represents a new host and geographical record and reinforces the interest to further study the parasite diversity of wild ungulates for a better understanding of complex host-parasite associations and biogeography.

Multispecies helminth parasitism of grazing dairy cows in Germany and Austria, examined in the housing period.

Helminth composition and burden data for dairy cows have not been reported for >40 years for Germany and even less information is available for Austria. In the context of two recent studies, helminth parasitism was studied in 32 cows (23 from six farms in Bavaria and Tyrol; 9 from one farm in Saxony) from pasture-based dairy farms necropsied during the housing period. Helminths were enumerated and identified based on morphological characters (all helminths but rumen flukes) or molecular techniques (rumen flukes). Thirteen species of gastrointestinal nematodes and two species each of liver flukes (Fasciola hepatica, Dicrocoelium dendriticum) and rumen flukes (Calicophoron daubneyi, Paramphistomum leydeni) were recorded; no lungworms were recovered from any cow. Early fourth-stage (inhibited) larval Ostertagia species nematodes (210 to 140,600) were recovered from all cows, 31 each had adult Ostertagia ostertagi/Ostertagia lyrata (40 to 2020) and Trichostrongylus axei (10 to 53,400), 23 Oesophagostomum radiatum (1 to 242) and 20 Cooperia punctata (10 to 3330). Other nematodes present in descending order of prevalence were: Cooperia oncophora/Cooperia surnabada, Ostertagia leptospicularis/Ostertagia kolchida, Oesophagostomum venulosum, Bunostomum phlebotomum, Chabertia ovina, Nematodirus helvetianus, Trichostrongylus longispicularis, Haemonchus contortus and Aonchotheca bilobata. The cows from Bavaria and Tyrol harbored more total gastrointestinal nematodes than that from Saxony (geometric mean adult plus inhibited larval nematodes, 6510 vs. 2051, respectively). However, in both cohorts of cows abomasal nematodes accounted for ∼97% of the total nematode burden with inhibited larval Ostertagia species nematodes contributing over 70% of the total gastrointestinal nematode burden and âˆ¼ 96% of the Ostertagia species burden. Approximately 44%, 37% and 19% of the cows harbored <5000, 5000 to 10,000 or > 10,000 total gastrointestinal nematodes, respectively. Fecal nematode egg and coproculture nematode larval counts significantly correlated with the cows' total adult nematode burden (rs = 0.354, p < 0.05, and rs = 0.608, p < 0.001, respectively). Although the magnitude of nematode burden to exert production effects on dairy cows is not well defined and may vary relative to several factors including nutritional supplementation, the level of mixed parasitism found in this investigation supports consideration of grazing dairy cows in helminth control measures, especially at the time of housing in autumn.

Eprinomectin 5% w/v extended-release injection for the treatment of larval and/or adult Bunostomum phlebotomum, Haemonchus contortus, H. placei, Nematodirus helvetianus, Oesophagostomum radiatum, and Trichostrongylus colubriformis infections in cattle.

In an effort to generate data for regulatory purposes on the therapeutic efficacy of eprinomectin 5% w/v extended-release injection (Eprinomectin ERI) (LongRange®, Boehringer Ingelheim) against infections of immature and adult stages of some nematode species (or stages) which are generally less common or predominantly seen in younger cattle, nine studies (minimum two per parasite and stage) were conducted in the USA and Germany. A total of 218 young cattle were included in seven experimentally induced infection studies (180 animals) and two studies with naturally acquired nematode infections (38 animals), which were compliant with WAAVP and VICH guidelines. In each study, cattle were randomly assigned into groups which received 1 mL per 50 kg body weight of either saline (controls) or Eprinomectin ERI (equivalent to 1 mg eprinomectin per kg body weight) via subcutaneous injection when the parasites were developing fourth-stage larval (L4) or adult nematodes. Following necropsy and parasite recovery, percentage efficacy was calculated based on the comparison of geometric mean nematode counts of the Eprinomectin ERI- vs. the saline-treated animals. Eprinomectin ERI-treated cattle had significantly (p < 0.05) lower counts of each species and stage of nematodes than the controls. Eprinomectin ERI treatment was demonstrated to be efficacious (> 90%) against L4 and adult Bunostomum phlebotomum and Nematodirus helvetianus; against L4 Haemonchus placei, Oesophagostomum radiatum, and Trichostrongylus colubriformis; and against adult H. contortus. Percentage efficacy against L4 H. contortus was variable (69.6 to 100%). All treatments were well accepted, and no treatment-related health problems were observed in any study.

Distribution, prevalence, and intensity of Sarcocystis infections in sika deer (Cervus nippon) of free-ranging populations in Germany and Austria.

Sika deer (Cervus nippon), which are native to the Japanese islands and the adjacent mainland of eastern Asia, have been introduced into Europe and established free-ranging populations in several countries. Various Sarcocystis species have been identified recently from farmed "mainland sika" deer in Lithuania and native "Japanese sika" deer in Japan. To study the distribution, prevalence and intensity of Sarcocystis infection in free-ranging sika deer outside of their natural range heart and/or diaphragm samples of 311 animals from nine populations in Germany and Austria were examined by histology.Overall, sarcocysts were detected in either heart or diaphragm of 107/311 deer (34.4%) with prevalence ranging roughly from 5 to 50% among the populations. Considering the 263 animals with both heart and diaphragm available, prevalence varied significantly (p < 0.0001) among calves (20.2%), yearlings (40.3%), and adult deer (49.1%) but did not differ between male and female deer (48.3% vs. 43.7%; p = 0.6483). Occurrence of sarcocysts in heart vs. diaphragm indicated a marginal difference (27.8% vs. 20.9%; p = 0.0839). Intensity of infection in all but one heart positive and all diaphragm positive animals was low (< 10 sarcocysts per square centimeter muscle cut). While heart sarcocyst counts of yearlings and adult deer were higher than those of calves and were higher in male compared to female sika deer, diaphragm sarcocyst counts did not differ significantly between age groups and sexes. Sarcocystis infection was demonstrated at variable prevalence in sika deer in all populations but intensity is apparently low. Further studies are needed to identify the species of Sarcocystis infecting sika deer naturalized outside their natural range.

Treatment of natural Protostrongylus rufescens lungworm infection in sheep with eprinomectin 5 mg/mL topical solution.

Parasitic respiratory infections in domestic sheep and goats are caused by Dictyocaulus filaria and various species belonging to the Protostrongylidae family of nematodes which frequently occur in mixed infections. Although the parasitism with protostrongylid lungworms is generally considered to be of low pathogenicity, there are reports of clinical disease including cases associated with Protostrongylus rufescens infection. The efficacy against P. rufescens of eprinomectin 5 mg/mL topical solution (EPRINEX® Multi, Boehringer Ingelheim) was thus evaluated in a clinical study compliant with GCP and VICH anthelmintic efficacy testing guidelines in adult sheep with naturally acquired infection. Following ranking on pre-treatment Protostrongylus fecal larval counts and forming into blocks of two animals, the sheep were randomly allocated to either remain untreated (control) or to be administered eprinomectin 5 mg/mL topical solution at 1 mL/5 kg body weight (equivalent to 1 mg eprinomectin per kg body weight) once as a pour-on. Fecal samples of the sheep were examined to monitor the larval excretion weekly for five weeks after treatment; then the animals were necropsied for lungworm recovery and count to determine the efficacy of the treatment. After treatment, Protostrongylus larval excretion decreased to zero within three weeks. Nematode counts demonstrated that the efficacy of the treatment with eprinomectin 5 mg/mL topical solution was 100 % against P. rufescens: no lungworms were recovered from any treated sheep while all controls harbored P. rufescens (range, 17-406) (p < 0.001). The treatment was well accepted; no treatment-related health problems were observed.

Sika Deer (Cervus nippon) are not "Dead-End Hosts" of the Giant Liver Fluke, Fascioloides magna (Bassi, 1875) Ward, 1917.

Fascioloides magna, although of North American origin, is well established in central Europe. Here it is expanding its geographic range and has been exposed to new potential final hosts including native and naturalized species. Based on their contribution to the propagation and transmission of F. magna, its final hosts have been grouped into three types including 'dead-end hosts' that comprise species in which flukes reach the liver but rarely mature and produce few eggs which are not excreted. Sika deer (Cervus nippon) were classified as dead-end hosts, this being quoted in the literature without robust substantiation. In an investigation on the occurrence of F. magna among sympatric wild ungulates in a recently established focus of the parasite in Germany, nine of 24 sika deer were found infected with up to seven F. magna in their livers, and six of the fluke-positive sika deer had Fascioloides eggs in their feces. Most flukes were recovered in pairs from fibrous capsules. Associated with the low fluke burden, gross pathology of the livers was generally mild. The presence of mature flukes in fibrous capsules, and passing of ova in the feces, demonstrates sika deer to be suitable definitive hosts of F. magna and to be of epidemiologic significance because of their implication in the transmission of the fluke.

On the cutting edge of glioblastoma surgery: where neurosurgeons agree and disagree on surgical decisions.

OBJECTIVE: The aim of glioblastoma surgery is to maximize the extent of resection while preserving functional integrity. Standards are lacking for surgical decision-making, and previous studies indicate treatment variations. These shortcomings reflect the need to evaluate larger populations from different care teams. In this study, the authors used probability maps to quantify and compare surgical decision-making throughout the brain by 12 neurosurgical teams for patients with glioblastoma. METHODS: The study included all adult patients who underwent first-time glioblastoma surgery in 2012-2013 and were treated by 1 of the 12 participating neurosurgical teams. Voxel-wise probability maps of tumor location, biopsy, and resection were constructed for each team to identify and compare patient treatment variations. Brain regions with different biopsy and resection results between teams were identified and analyzed for patient functional outcome and survival. RESULTS: The study cohort consisted of 1087 patients, of whom 363 underwent a biopsy and 724 a resection. Biopsy and resection decisions were generally comparable between teams, providing benchmarks for probability maps of resections and biopsies for glioblastoma. Differences in biopsy rates were identified for the right superior frontal gyrus and indicated variation in biopsy decisions. Differences in resection rates were identified for the left superior parietal lobule, indicating variations in resection decisions. CONCLUSIONS: Probability maps of glioblastoma surgery enabled capture of clinical practice decisions and indicated that teams generally agreed on which region to biopsy or to resect. However, treatment variations reflecting clinical dilemmas were observed and pinpointed by using the probability maps, which could therefore be useful for quality-of-care discussions between surgical teams for patients with glioblastoma.

Pour-on administration of eprinomectin to lactating dairy goats: Pharmacokinetics and anthelmintic efficacy.

Lactation is discussed as a physiological covariate which may influence the exposure characteristics of systemically acting drugs including macrocyclic lactones and potentially alter their pharmacological response. This study characterizes for the first time in the same study, the plasma profile and therapeutic anthelmintic efficacy of eprinomectin 5 mg/ml solution (EPRINEX® Multi, Boehringer Ingelheim) administered as a pour-on at 1 mg per kg body weight to lactating dairy goats. The study was conducted in compliance with VICH GCP and anthelmintic efficacy evaluation guidelines and included 20 goats harboring induced adult gastrointestinal and pulmonary nematode infections. The goats were blocked on pre-treatment body weight and randomly allocated either to remain untreated (control) or to be eprinomectin-treated. Plasma samples to determine the plasma disposition kinetics of eprinomectin (B1a component) were obtained at intervals up to 14 days following treatment when the animals were necropsied for parasite enumeration and identification. Basic pharmacokinetic parameters of eprinomectin determined in the ten eprinomectin-treated goats were as follows: AUClast , 23.8 ± 9.7 day*ng/ml and Cmax , 5.35 ± 2.27 ng/ml; individual maximum plasma concentrations were observed from 8 to 48 h after treatment (median Tmax , 0.5 days). Topical eprinomectin treatment efficacy, based on significant (p < .01) worm burden reductions in eprinomectin-treated animals relative to untreated controls, was ≥97% to 100% against adult Dictyocaulus filaria, Haemonchus contortus, Teladorsagia circumcincta(pinnata/trifurcata), Trichostrongylus axei, T. colubriformis, Cooperia curticei, Nematodirus battus, and Oesophagostomum venulosum. Both pharmacokinetic parameters and anthelmintic activity in lactating dairy goats were similar to those observed in parasitized young growing and adult female non-lactating dairy goats treated with eprinomectin administered as a pour-on.

Timing of glioblastoma surgery and patient outcomes: a multicenter cohort study.

BACKGROUND: The impact of time-to-surgery on clinical outcome for patients with glioblastoma has not been determined. Any delay in treatment is perceived as detrimental, but guidelines do not specify acceptable timings. In this study, we relate the time to glioblastoma surgery with the extent of resection and residual tumor volume, performance change, and survival, and we explore the identification of patients for urgent surgery. METHODS: Adults with first-time surgery in 2012-2013 treated by 12 neuro-oncological teams were included in this study. We defined time-to-surgery as the number of days between the diagnostic MR scan and surgery. The relation between time-to-surgery and patient and tumor characteristics was explored in time-to-event analysis and proportional hazard models. Outcome according to time-to-surgery was analyzed by volumetric measurements, changes in performance status, and survival analysis with patient and tumor characteristics as modifiers. RESULTS: Included were 1033 patients of whom 729 had a resection and 304 a biopsy. The overall median time-to-surgery was 13 days. Surgery was within 3 days for 235 (23%) patients, and within a month for 889 (86%). The median volumetric doubling time was 22 days. Lower performance status (hazard ratio [HR] 0.942, 95% confidence interval [CI] 0.893-0.994) and larger tumor volume (HR 1.012, 95% CI 1.010-1.014) were independently associated with a shorter time-to-surgery. Extent of resection, residual tumor volume, postoperative performance change, and overall survival were not associated with time-to-surgery. CONCLUSIONS: With current decision-making for urgent surgery in selected patients with glioblastoma and surgery typically within 1 month, we found equal extent of resection, residual tumor volume, performance status, and survival after longer times-to-surgery.

Efficacy of a topical combination of eprinomectin, praziquantel, fipronil and (S)-methoprene against developing and adult Troglostrongylus brevior lungworms (Nematoda, Crenosomatidae) in cats.

The efficacy of the eprinomectin, praziquantel, fipronil and (S)-methoprene combination parasiticide Broadline® (Boehringer Ingelheim Animal Health) was evaluated against developing larval and adult stages of Troglostrongylus brevior, a metastrongyloid pulmonary nematode which is reported to parasitize domestic cats in southern Europe with increasing frequency. Twenty four purpose-bred cats were experimentally infected with 100 third-stage T. brevior larvae each and randomly allocated to either remain untreated (control) or to be treated with the combination product when T. brevior were developing larval (6 days post inoculation, dpi) or adult nematodes (28 dpi) (eight cats per group). Treatments were administered topically at the minimum label dose of 0.12 mL/kg. Fecal samples of the cats were examined to confirm the presence of patent (adult) nematode infections prior to treatment at 28 dpi and to monitor the larval excretion. At necropsy (49 dpi), the weight of the pulmonary lymph nodes and lungs were determined, and T. brevior lungworms were recovered and counted. All control animals and cats to be treated at 28 dpi excreted T. brevior larvae 24 dpi and 26 dpi while no larvae were excreted by the cats treated at 6 dpi. Following treatment at 28 dpi, T. brevior larval excretion decreased immediatetly and ceased prior to necropsy. Nematode counts demonstrated that treatment with the combination product was 100 % efficacious against both developing larval and adult T. brevior: no lungworms were recovered from any treated cat while all control animals harbored T. brevior (range, 6-52) (p < 0.001). No treatment-related health problems or any other clinical signs were observed in the cats. However, significantly higher absolute and relative (organ weight to body weight ratio) pulmonary lymph node weights of the control animals compared with the treated cats at 6 dpi (p < 0.001 and p < 0.001, respectively) and at 28 dpi (p = 0.003 and p = 0.019, respectively) indicated the pathology of the T. brevior infection. In conclusion, the combination product was demonstrated to be 100 % efficacious against developing larval and adult T. brevior. Furthermore, it was demonstrated that indicators of impaired respiratory and immune systems resultant from T. brevior infection can be prevented with an efficacious treatment when administered during the pre-patent period of infection or are improving substantially within three weeks of treatment of cats harboring adult lungworms.

Efficacy of Broadline® in cats against induced infections with developing fourth-stage larval and adult Ancylostoma ceylanicum hookworms.

Ancylostoma ceylanicum hookworms parasitize dogs and cats in subtropical and tropical South East Asia and Pacific region, the Arab Peninsula, southern Africa and South America but cause patent infections in humans too. To evaluate the efficacy of Broadline®, a combination product comprising eprinomectin, fipronil, (S)-methoprene and praziquantel, against developing fourth-larval stage (L4) and adult A. ceylanicum in cats, a blinded, induced infection study was conducted. Following oral inoculation of 24 purpose bred cats with ˜300 infectious A. ceylanicum larvae each, cats were allocated to one of three groups of eight animals, each which served either as untreated controls or received Broadline® (once topically at the minimum label dose of 0.12 mL per kg bodyweight) when the hookworms were L4 (five days post inoculation, dpi) or adults (25 dpi). Efficacy was determined on nematode counts following necropsy of the cats. Fecal examination at 22 dpi confirmed that all cats of the control group and of the group to be treated when the hookworms were adult were excreting hookworm eggs (range, 100 to 1000 eggs per gram) while no eggs were recovered from the feces of the cats treated with Broadline® 5 dpi. Nematode counts established 35 dpi demonstrated that Broadline® treatment was 100% efficacious against both, developing L4 and adult A. ceylanicum: no hookworms were recovered from any Broadline®-treated cat while all control animals harbored A. ceylanicum (range, 8-35) (p < 0.001). No health problems were observed throughout the study.

Accurate MR Image Registration to Anatomical Reference Space for Diffuse Glioma.

To summarize the distribution of glioma location within a patient population, registration of individual MR images to anatomical reference space is required. In this study, we quantified the accuracy of MR image registration to anatomical reference space with linear and non-linear transformations using estimated tumor targets of glioblastoma and lower-grade glioma, and anatomical landmarks at pre- and post-operative time-points using six commonly used registration packages (FSL, SPM5, DARTEL, ANTs, Elastix, and NiftyReg). Routine clinical pre- and post-operative, post-contrast T1-weighted images of 20 patients with glioblastoma and 20 with lower-grade glioma were collected. The 2009a Montreal Neurological Institute brain template was used as anatomical reference space. Tumors were manually segmented in the patient space and corresponding healthy tissue was delineated as a target volume in the anatomical reference space. Accuracy of the tumor alignment was quantified using the Dice score and the Hausdorff distance. To measure the accuracy of general brain alignment, anatomical landmarks were placed in patient and in anatomical reference space, and the landmark distance after registration was quantified. Lower-grade gliomas were registered more accurately than glioblastoma. Registration accuracy for pre- and post-operative MR images did not differ. SPM5 and DARTEL registered tumors most accurate, and FSL least accurate. Non-linear transformations resulted in more accurate general brain alignment than linear transformations, but tumor alignment was similar between linear and non-linear transformation. We conclude that linear transformation suffices to summarize glioma locations in anatomical reference space.

Quantifying eloquent locations for glioblastoma surgery using resection probability maps.

OBJECTIVE: Decisions in glioblastoma surgery are often guided by presumed eloquence of the tumor location. The authors introduce the "expected residual tumor volume" (eRV) and the "expected resectability index" (eRI) based on previous decisions aggregated in resection probability maps. The diagnostic accuracy of eRV and eRI to predict biopsy decisions, resectability, functional outcome, and survival was determined. METHODS: Consecutive patients with first-time glioblastoma surgery in 2012-2013 were included from 12 hospitals. The eRV was calculated from the preoperative MR images of each patient using a resection probability map, and the eRI was derived from the tumor volume. As reference, Sawaya's tumor location eloquence grades (EGs) were classified. Resectability was measured as observed extent of resection (EOR) and residual volume, and functional outcome as change in Karnofsky Performance Scale score. Receiver operating characteristic curves and multivariable logistic regression were applied. RESULTS: Of 915 patients, 674 (74%) underwent a resection with a median EOR of 97%, functional improvement in 71 (8%), functional decline in 78 (9%), and median survival of 12.8 months. The eRI and eRV identified biopsies and EORs of at least 80%, 90%, or 98% better than EG. The eRV and eRI predicted observed residual volumes under 10, 5, and 1 ml better than EG. The eRV, eRI, and EG had low diagnostic accuracy for functional outcome changes. Higher eRV and lower eRI were strongly associated with shorter survival, independent of known prognostic factors. CONCLUSIONS: The eRV and eRI predict biopsy decisions, resectability, and survival better than eloquence grading and may be useful preoperative indices to support surgical decisions.

Efficacy of a topical combination of eprinomectin, praziquantel, fipronil and (S)-methoprene against developing and adult Troglostrongylus brevior lungworms (Nematoda, Crenosomatidae) in cats.

The efficacy of the eprinomectin, praziquantel, fipronil and (S)-methoprene combination parasiticide Broadline® (Boehringer Ingelheim Animal Health) was evaluated against developing larval and adult stages of Troglostrongylus brevior, a metastrongyloid pulmonary nematode which is reported to parasitize domestic cats in southern Europe with increasing frequency. Twenty four purpose-bred cats were experimentally infected with 100 third-stage T. brevior larvae each and randomly allocated to either remain untreated (control) or to be treated with the combination product when T. brevior were developing larval (6 days post inoculation, dpi) or adult nematodes (28 dpi) (eight cats per group). Treatments were administered topically at the minimum label dose of 0.12mL/kg. Fecal samples of the cats were examined to confirm the presence of patent (adult) nematode infections prior to treatment at 28 dpi and to monitor the larval excretion. At necropsy (49 dpi), the weight of the pulmonary lymph nodes and lungs were determined, and T. brevior lungworms were recovered and counted. All control animals and cats to be treated at 28 dpi excreted T. brevior larvae 24 dpi and 26 dpi while no larvae were excreted by the cats treated at 6 dpi. Following treatment at 28 dpi, T. brevior larval excretion decreased immediatetly and ceased prior to necropsy. Nematode counts demonstrated that treatment with the combination product was 100 % efficacious against both developing larval and adult T. brevior: no lungworms were recovered from any treated cat while all control animals harbored T. brevior (range, 6-52) (p<0.001). No treatment-related health problems or any other clinical signs were observed in the cats. However, significantly higher absolute and relative (organ weight to body weight ratio) pulmonary lymph node weights of the control animals compared with the treated cats at 6 dpi (p<0.001 and p<0.001, respectively) and at 28 dpi (p=0.003 and p=0.019, respectively) indicated the pathology of the T. brevior infection. In conclusion, the combination product was demonstrated to be 100 % efficacious against developing larval and adult T. brevior. Furthermore, it was demonstrated that indicators of impaired respiratory and immune systems resultant from T. brevior infection can be prevented with an efficacious treatment when administered during the pre-patent period of infection or are improving substantially within three weeks of treatment of cats harboring adult lungworms.

Efficacy of Broadline® in cats against induced infections with developing fourth-stage larval and adult Ancylostoma ceylanicum hookworms.

Ancylostomaceylanicum hookworms parasitize dogs and cats in subtropical and tropical South East Asia and Pacific region, the Arab Peninsula, southern Africa and South America but cause patent infections in humans too. To evaluate the efficacy of Broadline®, a combination product comprising eprinomectin, fipronil, (S)-methoprene and praziquantel, against developing fourth-larval stage (L4) and adult A. ceylanicum in cats, a blinded, induced infection study was conducted. Following oral inoculation of 24 purpose bred cats with ˜300 infectious A. ceylanicum larvae each, cats were allocated to one of three groups of eight animals, each which served either as untreated controls or received Broadline® (once topically at the minimum label dose of 0.12mL per kg bodyweight) when the hookworms were L4 (five days post inoculation, dpi) or adults (25 dpi). Efficacy was determined on nematode counts following necropsy of the cats. Fecal examination at 22 dpi confirmed that all cats of the control group and of the group to be treated when the hookworms were adult were excreting hookworm eggs (range, 100 to 1000 eggs per gram) while no eggs were recovered from the feces of the cats treated with Broadline® 5 dpi. Nematode counts established 35 dpi demonstrated that Broadline® treatment was 100% efficacious against both, developing L4 and adult A. ceylanicum: no hookworms were recovered from any Broadline®-treated cat while all control animals harbored A. ceylanicum (range, 8-35) (p<0.001). No health problems were observed throughout the study.

Robust Deep Learning-based Segmentation of Glioblastoma on Routine Clinical MRI Scans Using Sparsified Training.

PURPOSE: To improve the robustness of deep learning-based glioblastoma segmentation in a clinical setting with sparsified datasets. MATERIALS AND METHODS: In this retrospective study, preoperative T1-weighted, T2-weighted, T2-weighted fluid-attenuated inversion recovery, and postcontrast T1-weighted MRI from 117 patients (median age, 64 years; interquartile range [IQR], 55-73 years; 76 men) included within the Multimodal Brain Tumor Image Segmentation (BraTS) dataset plus a clinical dataset (2012-2013) with similar imaging modalities of 634 patients (median age, 59 years; IQR, 49-69 years; 382 men) with glioblastoma from six hospitals were used. Expert tumor delineations on the postcontrast images were available, but for various clinical datasets, one or more sequences were missing. The convolutional neural network, DeepMedic, was trained on combinations of complete and incomplete data with and without site-specific data. Sparsified training was introduced, which randomly simulated missing sequences during training. The effects of sparsified training and center-specific training were tested using Wilcoxon signed rank tests for paired measurements. RESULTS: A model trained exclusively on BraTS data reached a median Dice score of 0.81 for segmentation on BraTS test data but only 0.49 on the clinical data. Sparsified training improved performance (adjusted P < .05), even when excluding test data with missing sequences, to median Dice score of 0.67. Inclusion of site-specific data during sparsified training led to higher model performance Dice scores greater than 0.8, on par with a model based on all complete and incomplete data. For the model using BraTS and clinical training data, inclusion of site-specific data or sparsified training was of no consequence. CONCLUSION: Accurate and automatic segmentation of glioblastoma on clinical scans is feasible using a model based on large, heterogeneous, and partially incomplete datasets. Sparsified training may boost the performance of a smaller model based on public and site-specific data.Supplemental material is available for this article.Published under a CC BY 4.0 license.

Comparing Glioblastoma Surgery Decisions Between Teams Using Brain Maps of Tumor Locations, Biopsies, and Resections.

PURPOSE: The aim of glioblastoma surgery is to maximize the extent of resection while preserving functional integrity, which depends on the location within the brain. A standard to compare these decisions is lacking. We present a volumetric voxel-wise method for direct comparison between two multidisciplinary teams of glioblastoma surgery decisions throughout the brain. METHODS: Adults undergoing first-time glioblastoma surgery from 2012 to 2013 performed by two neuro-oncologic teams were included. Patients had had a diagnostic biopsy or resection. Preoperative tumors and postoperative residues were segmented on magnetic resonance imaging in three dimensions and registered to standard brain space. Voxel-wise probability maps of tumor location, biopsy, and resection were constructed for each team to compare patient referral bias, indication variation, and treatment variation. To evaluate the quality of care, subgroups of differentially resected brain regions were analyzed for survival and functional outcome. RESULTS: One team included 101 patients, and the other included 174; 91 tumors were biopsied, and 181 were resected. Patient characteristics were largely comparable between teams. Distributions of tumor locations were dissimilar, suggesting referral bias. Distributions of biopsies were similar, suggesting absence of indication variation. Differentially resected regions were identified in the anterior limb of the right internal capsule and the right caudate nucleus, indicating treatment variation. Patients with (n = 12) and without (n = 6) surgical removal in these regions had similar overall survival and similar permanent neurologic deficits. CONCLUSION: Probability maps of tumor location, biopsy, and resection provide additional information that can inform surgical decision making across multidisciplinary teams for patients with glioblastoma.

Eprinomectin pour-on: Prevention of gastrointestinal and pulmonary nematode infections in sheep.

The present study was conducted to further characterize the anthelmintic activity of the 0.5% w/v topical formulation of eprinomectin (EPRINEX® Pour-on, Merial) when administered at 1 mg/kg body weight to sheep in preventing the establishment of induced gastrointestinal and pulmonary nematode infections. Thirty-six female Merino sheep (∼4 months of age, weighing 27.0-36.0 kg) were blocked by pre-treatment body weight to form blocks of four animals. Within blocks, the animals were randomly allocated to either remain untreated (control) or be treated once with EPRINEX® either on Day 0, Day 7 or Day 14. Starting on Day 15, the sheep were given trickle infections with infective larvae of seven species of gastrointestinal nematodes and Dictyocaulus filaria lungworms daily for seven consecutive days. Five weeks after completion of the daily challenge (Day 56), the animals were necropsied for parasite recovery and count. Treatment with EPRINEX® prevented the establishment (>90%, p ≤ 0.027) of D. filaria, Teladorsagia circumcincta (pinnata/trifurcata), Cooperia curticei, Nematodirus battus, Trichostrongylus colubriformis and Oesophagostomum venulosum for at least 21 days, and of Haemonchus contortus and Trichostrongylus axei for at least 14 days. Sheep in the groups treated with EPRINEX® at Days 7 and 14 had significantly (p ≤ 0.018) higher Day -1 to Day 56 wt gains than the untreated controls. No treatment-related health problems or any other health problems were observed throughout the study.

Eprinomectin pour-on (EPRINEX® Pour-on, Merial): efficacy against gastrointestinal and pulmonary nematodes and pharmacokinetics in sheep.

BACKGROUND: The anthelmintic efficacy of the 0.5% w/v topical formulation of eprinomectin (EPN), EPRINEX® Pour-on (Merial) when administered at 1 mg/kg body weight was evaluated in sheep in two dose confirmation laboratory studies and one multicenter field study. In addition, the pharmacokinetics of EPN when administered at that dosage to adult sheep was determined. RESULTS: In the two dose confirmation studies, which included 10 sheep each, sheep treated with topical EPN had significantly (p < 0.05) fewer of the following nematodes than the untreated sheep with overall reduction of nematode counts by >99%: adult Dictyocaulus filaria, Haemonchus contortus, Teladorsagia circumcincta(pinnata/trifurcata), Trichostrongylus axei, T. colubriformis, T. vitrinus, Cooperia curticei, Nematodirus battus, Strongyloides papillosus, Chabertia ovina and Oesophagostomum venulosum, and inhibited fourth-stage Teladorsagia larvae. A total of 196 sheep harboring naturally acquired gastrointestinal nematode infections were included in the field efficacy study at two sites each in Germany (48 Merino x Ile de France lambs, 52 adult Merino females) and in Italy (adult male and female Bagnolese, Lacaune, Lacaune x Bagnolese, Bagnolese x Sarda sheep; 48 animals per site). Animals were blocked on pre-treatment body weight and within each block, one animal was randomly assigned to the control (untreated) group and three animals were randomly assigned to be treated with topical EPN. Examination of feces 14 days after treatment demonstrated that, relative to the controls, topical EPN-treated sheep had significantly (p < 0.0001) lower strongylid egg counts. Reduction was ≥97% at each site and 98.6% across all sites. Pharmacokinetics of EPN following single treatment with topical EPN were determined in eight ~4.5 year old female Merino cross sheep based on the analysis of plasma samples which were collected from two hours to 21 days following treatment. The main pharmacokinetic parameters were: Cmax 6.20 ± 1.71 ng/mL, AUClast 48.8 ± 19.2 day*ng/mL, Tmax 3.13 ± 2.99 days and T1/2 6.40 ± 2.95 days. No treatment-related health problems or adverse drug events were observed in any study. CONCLUSION: These studies demonstrated 0.5% w/v EPN administered topically at 1 mg/kg body weight to be highly efficacious against a broad range of ovine gastrointestinal nematodes and D. filaria lungworms and well tolerated by sheep of different ages, breeds, gender and physiological status.