A clinical screening tool to detect genetic cancer predisposition in pediatric oncology shows high sensitivity but can miss a substantial percentage of affected children.

PURPOSE: Clinical checklists are the standard of care to determine whether a child with cancer shows indications for genetic testing. Nevertheless, the efficacy of these tests to reliably detect genetic cancer predisposition in children with cancer is still insufficiently investigated. METHODS: We assessed the validity of clinically recognizable signs to identify cancer predisposition by correlating a state-of-the-art clinical checklist to the corresponding exome sequencing analysis in an unselected single-center cohort of 139 child-parent data sets. RESULTS: In total, one-third of patients had a clinical indication for genetic testing according to current recommendations, and 10.1% (14 of 139) of children harbored a cancer predisposition. Of these, 71.4% (10 of 14) were identified through the clinical checklist. In addition, >2 clinical findings in the checklist increased the likelihood to identifying genetic predisposition from 12.5% to 50%. Furthermore, our data revealed a high rate of genetic predisposition (40%, 4 of 10) in myelodysplastic syndrome cases, while no (likely) pathogenic variants were identified in the sarcoma and lymphoma group. CONCLUSION: In summary, our data show high checklist sensitivity, particularly in identifying childhood cancer predisposition syndromes. Nevertheless, the checklist used here also missed 29% of children with a cancer predisposition, highlighting the drawbacks of sole clinical evaluation and underlining the need for routine germline sequencing in pediatric oncology.

Prevention of Intramammary Infections by Prepartum External Application of a Teat Dip Containing Lactic Acid Bacteria with Antimicrobial Properties in Dairy Heifers.

The aim of the current study was to investigate the effects of the prepartum external treatment of teats with a combination of four lactic acid bacteria strains viz. Lactobacillus (Lb.) rhamnosus ATCC 7469, Lactococcus lactis subsp. lactis ATCC 11454, Lb. paracasei 78/37 (DSM 26911), and Lb. plantarum 118/37 (DSM 26912) on the postcalving udder health of dairy heifers. The study used a split-udder design. Two weeks before the expected calving date, one of two contralateral teats of a teat pair was dipped with an aqueous suspension of lactic acid bacteria (final bacterial counts 8.40-8.47 log10-transformed CFU/mL) once in a week until calving; the other teat of the pair was not treated. After calving, quarter foremilk samples were taken and investigated cyto-microbiologically. In total, 629 teat pairs of 319 heifers were included. There was an association between the treatment and intramammary infections caused by the major udder-pathogenic bacteria Staphylococcus aureus, Streptococcus dysgalactiae, and enterococci, as well as clinical mastitis in the first 100 days after calving. The present study indicates that intramammary infections with major pathogens and clinical mastitis may be prevented by regular prepartum external application of lactic acid bacteria in dairy heifers.

A field study evaluation of Petrifilm™ plates as a 24-h rapid diagnostic test for clinical mastitis on a dairy farm.

Clinical mastitis is one of the most common and expensive diseases of dairy cattle. To make an informed treatment decision, it is important to know the causative pathogen. However, no detection of bacterial growth can be made in approximately 30% of all clinical cases of mastitis. Before selecting the treatment regimen, it is important to know whether the mastitis-causing pathogen (MCP) is Gram-positive or Gram-negative. The aim of this field study was to investigate whether using two 3M Petrifilm™ products on-farm (which conveys a higher degree of sample freshness but also bears a higher risk for contamination than working in a lab) as 24-h rapid diagnostic of clinical mastitis achieved results that were comparable to the conventional microbiological diagnostic method. AerobicCount (AC)-Petrifilm™ and ColiformCount (CC)-Petrifilm™ were used to identify the total bacterial counts and Gram-negative bacteria in samples from clinical mastitis cases, respectively. Missing growth on both plates was classified as no bacterial detection. Growth only on the AC-Petrifilm™ was assessed as Gram-positive, and growth on both Petrifilm™ plates was assessed as Gram-negative bacterial growth. Additionally, milk samples were analysed by conventional microbiological diagnostic method on aesculin blood agar as a reference method. Overall, 616 samples from clinical mastitis cases were analysed. Using the reference method, Gram-positive and Gram-negative bacteria, mixed bacterial growth, contaminated samples and yeast were determined in 32.6%, 20.0%, 2.5%, 14.1% and 1.1% of the samples, respectively. In 29.7% of the samples, microbiological growth could not be identified. Using the Petrifilm™ concept, bacterial growth was detected in 59% of the culture-negative samples. The sensitivity of the Petrifilm™ for Gram-positive and Gram-negative MCP was 85.2% and 89.9%, respectively. The specificity was 75.4% for Gram-positive and 88.4% for Gram-negative MCP. For the culture-negative samples, sensitivity was 41.0% and specificity was 91.0%. The results indicate that the Petrifilm™ concept is suitable for therapeutic decision-making at the farm level or in veterinary practice. As this concept does not allow any statement about the genus or species of microorganisms, relevant MCP should be assessed periodically at the herd level with conventional microbiological diagnostics.

[Cure rates of chronic subclinical Staphylococcus aureus mastitis in lactating dairy cows after antibiotic therapy]. / Heilungsraten chronischer subklinischer Staphylococcus aureus-Mastitiden nach antibiotischer Therapie bei laktierenden Milchkühen.

Staphylococcus (S.) aureus is an important mastitis causing pathogen in dairy cows worldwide. The aim of this controlled and randomized study was to analyze the effects of an antibiotic treatment on chronic subclinical S.aureus mastitis during lactation.The study was conducted between July 2011 and December 2011 in Northern Germany including 134 udder quarters (i. e. 103 dairy cows) infected with S. aureus. The animals were randomly divided into two groups (control and treatment group). Quarter foremilk duplicate samples were taken on days 0, 7, 32 and 39 from each infected udder quarter for microbiological analysis and somatic cell count determination. Treatment consisted of cephalexin (200 mg intramammarily 5 times every 12 h) plus marbofloxacine (2 mg/kg BM subcutaneously 3 times every 24 h). "Pathogen elimination" was assessed as the status, when no S. aureus was isolated from the quarter samples of days 32 and 39. "Cure" was defined as the status, when in addition to pathogen elimination the somatic cell count of the quarter in both milk samples was below 100 000/ml. Animals of the treatment group showed a pathogen elimination rate of 35.9% and a cure rate of 21.9%. The rates for the control group were 21.4% and 8.6%, resp. The differences between groups were statistically significant. These results indicate that pathogen elimination and cure rates of chronic subclinical S. aureus mastitis are low after an intramammary cephalexin and subcutaneous marbofloxacine treatment, but still significantly better than without any antibiotic treatment.

[Effects of an additional nonsteroidal anti-inflammatory therapy with carprofen (Rimadyl Rind) in cases of severe mastitis of high yielding cows]. / Effekte einer zusätzlichen entzündungshemmenden Therapie mit Carprofen (Rimadyl Rind) bei schweren Mastitiden hochleistender Milchkühe.

This field study focuses on the possible effects of a combination of nonsteroidal anti-inflammatory treatment (carprofen) and a local and parenteral antibiotic on cure rates, survival rate and return to milk production of severe clinical mastitis cases. 69 cows in 3 herds (blocked by parity) with severe clinical mastitis during the first 120 d of lactation (median = 28 d) were treated with antibiotics and one-half of these cows were treated with 1.4 mg/kg bodyweight carprofen (Rimadyl Rind, Pfizer GmbH Tiergesundheit, Germany). Double milk samples for bacteriology were collected from clinically affected udder quarters before treatment and at 14 (+/- 3) and 21 (+/- 3) days after commencement of treatment for cytomicro-temperature, clinical, bacteriological, cytobacteriological cure rate and in the number of cows that were defined as treatment failures (i.e., died, re-treated, relapse). Six (22.2%) vs. seven (19.4%) cows in the carprofen and control groups failed, respectively. The milk yield was significantly higher in the carprofen-treated group compared with the control group after treatment. The present work gives first indications that treatment of cows with severe clinical mastitis with a combination of carprofen and antibiotics could result in a faster return to milk production compared to treatment with antibiotics alone. If this effect can be affiliated to the administration of carprofen alone has to be examined in further studies.

[Efficacy of extended intramammary therapy to treat moderate and severe clinical mastitis in lactating dairy cows]. / Wirksamkeit einer verlängerten Arzneimittelapplikation zur Behandlung mittel- und hochgradiger klinischer Mastitiden bei Milchkühen.

Streptococcus uberis and Staphylococcus aureus are important mastitis pathogens in dairy cows in the entire world. Recent publications showed that an extended therapy can be more efficient in combating such intramammary infections. The objective of this study was to evaluate the effect of an extended intramammary therapy to treat moderate and severe mastitis cases in lactating dairy cows under field conditions in northern Germany. From December 2005 to August 2007, a total of 157 clinical mastitis cases on 10 farms in northern Germany were enrolled in the study and randomly assigned (blocked by parity and body temperature) to one of two treatment groups (intrammammary lincomycin/neomycin 1.5-d (ALK) or 5-d (ALL)). Clinical, microbiological and cytomicrobiological cure rates were evaluated. Treatments were initiated before culture results. Cows were observed and evaluated on d 1 to 6, 19 and 26. Six cases in 157 (3.8%) resulted in a therapy change in between 48 h after mastitis detection. Overall, treatments were not significantly different to controls regarding clinical cure rate. However, when the microbiological cure rate was evaluated, differences were observed. ALL appeared form infections. We conclude that in farms with Streptococcus uberis mastitis, the 5-d extended lincomycin/neomycin treatment regimen was significantly more efficient in microbiological cure than the standard 1.5-d treatment.

Evaluation of increased milking frequency as an additional treatment for cows with clinical mastitis.

This field study focused on the possible effects of increased milking frequency (milking four times a day in comparison with milking twice a day) on clinical and bacteriological cure rates of clinical, antibiotically treated mastitis cases. Parameters tested were clinical, microbiological and full (cytomicrobiological) cure as well as the development of milk yield after the clinical mastitis episode. Cows from a large dairy herd meeting the study criteria (n=93) were assigned to two treatment groups by a systematic randomization scheme (blocked by body temperature <=or >39.5 degrees C). Both groups were randomly divided by experimental treatments: a) antibiotic intramammary treatment and milking 2-times a day; b) antibiotic intramammary treatment and milking 4-times a day. Treatments were initiated before the culture results were known. Cows were surveyed and evaluated on days 1-6, 24 and 31. No significant differences between treatment and control groups regarding clinical cure, microbiological cure, full cure and milk production could be established. Applying a 4-times a day milking regime did not lead to any significant effect, either positive or negative. Therefore, the results suggest that milking 4-times a day as a supporting therapy for mild, moderate and severe antimicrobially treated mastitis cases cannot be recommended.