Randomized controlled trial of pegbovigrastim as an adjunct therapy for naturally occurring severe clinical mastitis cases in dairy cows.

The main objective of this study was to quantify the effect of pegbovigrastim (PEG) as an adjunct therapy for naturally occurring severe mastitis cases on survival, intramammary bacteriological cure, and subsequent milk production. A double-blinded, randomized controlled trial was conducted on a single commercial dairy farm. During the study period, all cows having a case of severe clinical mastitis, defined as the presence of abnormal milk and inflammation in one quarter or more combined with the presence of systemic signs (pyrexia, dehydration, or recumbency), were enrolled in the study. In addition to a standardized therapy combining systemic and intramammary antimicrobials as well as systemic anti-inflammatory drugs, cows received a subcutaneous injection of either 2.7 mL of 0.9% sterile saline (control group; CON) or 2.7 mL of PEG (PEG group). A milk sample for bacteriological analysis was taken before treatment was administered and a second sample was taken 14 d after enrollment. Survival (30 d post-treatment) and bacteriological cure (14 d post-treatment) were analyzed by survival analysis and chi-squared tests, respectively, whereas daily milk production was treated as a repeated measure in mixed regression models. The 77 cows enrolled in the study were of parity 2 to 4 (mean = 3) and between 3 and 302 d in milk (mean = 154). The bacteria identified in milk at enrollment were Klebsiella spp. (n = 48; 62%), Escherichia coli (n = 16; 21%), Enterobacter spp. (n = 10; 13%), or no growth (n = 3; 4%). The probability of survival during the first 30 d after treatment was higher in the PEG group (84%) than in the control group (46%). Daily milk production over the 30-d period following treatment and bacteriological cure 14 d post-treatment did not differ between groups. Overall, cows treated with PEG as an adjunct therapy for naturally occurring cases of severe clinical mastitis had a better survival than cows treated with saline.

Short communication: Accuracy of corpus luteum color flow Doppler ultrasonography to diagnose nonpregnancy in dairy cows on day 21 after insemination.

The main objective of this study was to determine the accuracy of corpus luteum color flow Doppler ultrasonography (CLCFDU) to diagnose nonpregnant dairy cows 21 d after insemination. A secondary objective was to determine the accuracy of other indirect tests such as corpus luteum size and progesteronemia. Data from 1,632 Holstein cows (10 commercial herds) were used for the analysis in this prospective cohort study. The herds were visited weekly by a veterinarian and an animal health technician. During farm visits, cows were examined on d 21 after insemination using transrectal B-mode ultrasonography to quantify the presence and size of the corpus luteum. After identification of the corpus luteum, CLCFDU was performed and scored as D0, D1, D2, or D3 when 10% or less, between 11 and 30%, between 31 and 60%, or 61% or more of the corpus luteum surface was colored, respectively. A blood sample from coccygeal vessels was also collected to quantify progesteronemia. Farmers were blinded to these findings and no intervention was performed following examination. On d 32 after insemination, the cows were examined by the regular herd veterinarian using transrectal palpation and B-mode ultrasonography to determine whether the cows were pregnant or not (the reference test). Statistical analyses were conducted using 2 × 2 contingency tables. The apparent prevalence, sensitivity, specificity, positive predictive value, and negative predictive value of CLCFDU for predicting nonpregnancy were 22.0, 36.6, 99.0, 98.1, and 52.0%, respectively, when using D0 only as the diagnostic criterion; they were 47.2, 76.4, 94.8, 93.5, and 73.8%, respectively, for D0+D1 criteria. The same measures for cows with a corpus luteum <15 mm were 8.0, 11.7, 97.5, 86.9, and 43.4%, respectively, and they were 51.9, 67.4, 70.4, 76.6, and 60.0%, respectively, for progesteronemia <1 ng/mL. The measures of accuracy of CLCFDU to identify nonpregnant cows on d 21 after insemination were high, and the apparent prevalence varied depending on the diagnostic criteria used. The measures of accuracy of corpus luteum size (<15 mm) for the same purpose were high; however, apparent prevalence was low. The measures of accuracy of progesteronemia (<1 ng/mL) were low. In conclusion, CLCFDU had excellent accuracy to diagnose nonpregnancy in dairy cows on d 21 after insemination.

A randomized controlled trial on the effect of incomplete milking during the first 5 days in milk on reproductive performance of dairy cows.

The main objective of the current study was to measure the effect of incomplete milking on luteal activity and on pregnancy hazard. We also aimed to study the effect of early-lactation hyperketonemia (i.e., ß-hydroxybutyrate blood concentration ≥1.4 mmol/L during the first 3 wk in milk) on those reproductive outcomes. Multiparous Holstein cows (n = 853) from 13 commercial herds were enrolled in a randomized controlled trial. Cows were assigned to a control or a treatment group, incompletely milked (10-14 L of milk collected/d) from 1 to 5 DIM. Blood samples were collected once a week during weeks in milk 1 to 3 for ß-hydroxybutyrate blood concentration, and a threshold of 1.4 mmol/L was used to define hyperketonemia. During weeks in milk 5 and 7, cows were sampled for progesterone blood concentration, and a threshold of 1 ng/mL was used to define luteal activity. Reproductive information and culling dates were obtained through herd records. Logistic regression models and survival analyses were used to assess the effect of treatment on luteal activity and on pregnancy hazard, respectively. Analogous models were used to investigate the effect of early-lactation hyperketonemia on reproductive outcomes. The odds of luteal activity for incompletely milked cows were 1.1 (95% confidence interval: 0.72-1.7) times those of conventionally milked cows. The effect of treatment on pregnancy hazard varied as a function of time, parity, and start of the breeding period. In second-parity cows that started the breeding period <55 d in milk, the pregnancy hazard (95% confidence interval) in incompletely milked cows was 576.3 (240.0-1,383.7), 36.9 (18.9-72.1), 6.8 (3.3-13.8), 2.5 (1.0-5.9), and 0.13 (0.07-0.26) times that of conventionally milked cows at 1 to 21, 22 to 43, 44 to 65, 66 to 87, and >87 d after the voluntary waiting period, respectively. The treatment did not have an effect on pregnancy hazard in cows in third parity or greater or in those starting the breeding period ≥55 d in milk. Early-lactation hyperketonemia was not associated with any of the reproductive outcomes. In conclusion, the incomplete milking protocol had no effect on luteal activity and had a positive effect on pregnancy hazard in second-parity cows in herds with a short voluntary waiting period (<55 d). We did not observe an effect of early-lactation hyperketonemia on luteal activity or on pregnancy hazard.

Comparing the Health of Populations: Methods to Evaluate and Tailor Population Management Initiatives in the Netherlands.

Health care no longer focuses solely on patients and increasingly emphasizes regions and their populations. Strategies, such as population management (PM) initiatives, aim to improve population health and well-being by redesigning health care and community services. Hence, insight into population health is needed to tailor interventions and evaluate their effects. This study aims to assess whether population health differs between initiatives and to what extent demographic, personal, and lifestyle factors affect these differences. A population health survey that included the Short Form 12 version 2 (SF12, physical and mental health status), Patient Activation Measure 13 (PAM13), and demographic, personal, and lifestyle factors was administered in 9 Dutch PM initiatives. Potential confounders were determined by comparing these factors between PM initiatives using analyses of variance and chi-square tests. The influence of these potential confounders on the health outcomes was studied using multivariate linear regression. Age, education, origin, employment, body mass index, and smoking were identified as potential confounders for differences found between the 9 PM initiatives. Each had a noteworthy influence on all of the instruments' scores. Not all health differences between PM initiatives were explained, as the SF12 outcomes still differed between PM initiatives once corrected. For the PAM13, the differences were no longer significant. Demographic and lifestyle factors should be included in the evaluation of PM initiatives and population health differences found can be used to tailor initiatives. Other factors beyond health care (eg, air quality) should be considered to further refine the tailoring and evaluation of PM initiatives.

Characteristics and prognosis of interval cancers after biennial screen-film or full-field digital screening mammography.

We determined the characteristics and prognosis of interval breast cancers (IC) at screen-film (SFM) and full-field digital (FFDM) screening mammography. The study population consisted of 417,746 consecutive screening mammograms (302,699 SFM screens and 115,047 FFDM screens), obtained between 2000 and 2011. During 2-year follow-up, we collected breast imaging reports, surgical reports, and pathology results. A total of 800 ICs had been diagnosed in the screened population, of which 288 detected in the first year (early ICs) and 512 in the second year (late ICs) after a negative screen. 31.3 % of early IC's and 19.1 % of late IC's, respectively, were visible in retrospect on the latest previous screens, but had been missed during screening (P < 0.001). Missed invasive ICs were larger (28.5 mm vs. 23.9 mm, P = 0.003) and showed a higher fraction of T3+cancers (16.9 vs. 8.5 %, P = 0.02) than true ICs (i.e., not visible at the latest screen). A higher portion of missed than true ICs underwent mastectomy (44.7 vs. 30.8 %, P = 0.002). We found no differences in mammographic and tumor characteristics for early ICs, detected either after SFM or FFDM. Late ICs following FFDM were more often true ICs than missed ICs (69.0 vs. 57.6 %, P = 0.03) and more often receptor triple negative (P = 0.02), compared to late ICs at SFM. Interval cancer subgroups showed comparable overall survival. Interval cancer subgroups show distinctive mammographic and tumor characteristics but a comparable overall survival.

Type and Extent of Surgery for Screen-Detected and Interval Cancers at Blinded Versus Nonblinded Double-Reading in a Population-Based Screening Mammography Program.

BACKGROUND: This study aimed to compare the type and extent of surgery in patients with screen-detected and interval cancers after blinded or nonblinded double-reading of screening mammograms. METHODS: The study investigated a consecutive series of screens double-read in either a blinded (n = 44,491) or nonblinded (n = 42,996) fashion between 2009 and 2011. During a 2 year follow-up period, the radiology reports, surgical correspondence, and pathology reports of all the screen-detected and interval cancers were collected. RESULTS: Screen-detected breast cancer was diagnosed for 325 women at blinded and 284 women at nonblinded double-reading. The majority of the women were treated by breast-conserving surgery (BCS) at both reading strategies (78.2 vs. 81.7 %; p = 0.51). Larger total resection volumes were observed at BCS for ductal carcinoma in situ (DCIS) treatment for patients after blinded double-reading (p = 0.005). The proportions of positive resection margins after BCS were comparable for patients with DCIS (p = 0.81) or invasive screen-detected cancers (p = 0.38) for the two reading strategies. A total of 158 interval cancers were diagnosed. The proportions of patients treated with BCS were comparable for the two reading strategies (p = 0.42). The total resection volume (p = 0.13) and the proportion of positive resection margins after BCS (p = 0.32) for invasive interval cancer were comparable for the two cohorts. The BCS rate was higher for women after nonblinded double-reading (p = 0.04). CONCLUSIONS: Blinded and nonblinded double-reading yielded comparable surgical treatments for women with screen-detected or interval breast cancer except for larger total resection volumes at BCS for screen-detected DCIS and a higher BCS rate for interval cancers at nonblinded double-reading.

Comparison of the diagnostic workup of women referred at non-blinded or blinded double reading in a population-based screening mammography programme in the south of the Netherlands.

BACKGROUND: To determine whether referred women experience differences in diagnostic workup at non-blinded or blinded double reading of screening mammograms. METHODS: We included a consecutive series of respectively 42.996 and 44.491 screens, double read either in a non-blinded or blinded manner between 2009 and 2011. This reading strategy was alternated on a monthly basis. RESULTS: The overall ultrasound-guided core needle biopsy (CNB) rate and stereotactic CNB (SCNB) rate per 1000 screens were higher at blinded than at non-blinded reading (7.5 vs 6.0, P=0.008 and 8.1 vs 6.6, P=0.009). Among women with benign workup, these rates were higher at blinded reading (2.6 vs 1.4, P<0.001 and 5.9 vs 4.7, P=0.013). The benign biopsy rates were higher at blinded double reading (P<0.001), whereas the positive predictive value of biopsy did not differ (P=0.103). CONCLUSIONS: Blinded double-reading results in higher overall CNB and SCNB rates than non-blinded double reading, as well as a higher benign biopsy rate.

Screening outcome and surgical treatment during and after the transition from screen-film to digital screening mammography in the south of The Netherlands.

We determined screening outcome of subsequent screens during and after the transition from screen-film mammography (SFM) to full-field digital mammography (FFDM). A consecutive series of 102,863 subsequent (SFM screens with a prior SFM screen (SFM-SFM cohort), 91,941 FFDM screens with a prior SFM screen (FFDM-SFM cohort) and 90,407 FFDM screens with a prior FFDM screen (FFDM-FFDM cohort) were obtained between January 2006 and July 2013. The referral rate and cancer detection rate (CDR) per 1,000 screens were higher at FFDM-SFM than at SFM-SFM (2.7% vs. 1.2% (p < 0.001) and 7.0 vs. 4.9, p < 0.001), at the expense of a lower positive predictive value (PPV) of referral (25.8% vs. 39.6%, p < 0.001). These parameters were comparable for FFDM-SFM and FFDM-FFDM. Ductal carcinoma in situ (DCIS) and invasive cancer rates increased during transition and remained stable after transition. The rate of DCIS of intermediate grade increased during the transition from 0.2 per 1,000 screened women at SFM-SFM to 0.6 at FFDM-SFM (p < 0.001) and 0.5 at FFDM-FFDM (p = 0.001). Compared to SFM-SFM, a significantly higher rate of invasive cancers were stage T1a-b at FFDM-SFM (p < 0.001) and FFDM-FFDM (p < 0.001). Breast conserving surgery rates increased during transition (p < 0.001) and remained stable afterwards. The CDR and referral rate remained significantly higher at FFDM than at SFM, at the expense of a decreased PPV of referral. During transition, DCIS was more often of intermediate grade and invasive cancers were of smaller size.

Increased blood-circulating interferon-γ, interleukin-17, and osteopontin levels in bovine paratuberculosis.

Paratuberculosis-infected cattle initially develop an effective cell-mediated immune response that declines as the disease progresses. Blood is one of best sources for characterizing the inflammatory status of infected cows and for studying mediators related to chronic diseases. The aim of this study was to evaluate the cow-level association between blood cytokine concentration, the influence of serum on immune cell proliferation, and dairy cows naturally infected with Mycobacterium avium ssp. paratuberculosis (MAP). Positive animals (n=41) from 19 herds were selected on the basis of 2 positive fecal culture results and divided into 2 groups: single-positive, or serum ELISA-negative cows (n=32), and double-positive, or cows that gave positive results for both mycobacterial culture and serum ELISA (n=9). Negative animals (n=39) were selected from paratuberculosis-negative herds in which at least 80% of the animals had been diagnosed as negative by fecal culture and ELISA and that did not produce positive results during the 2-yr study. Analysis of plasma levels of the cytokines IL-4, IL-10, IL-17, IFN-γ, and osteopontin was performed, revealing distinct patterns. The ELISA-positive cows with MAP shedding had similar plasma concentrations of IL-4 and IL-10 but elevated levels of IFN-γ, IL-17, and osteopontin, which is indicative of inflammatory disease in these subclinical positive cows. In vitro MAP infection of bovine macrophages showed increased gene expression of tumor necrosis factor-α, IL-1ß, IL-6, IL-23, and transforming growth factor-ß as early as 6h postinfection for all of the cytokines involved in the establishment of a T-helper type-17 immune response. To determine the systemic influence of serum on immune cell functions, lymphoproliferation assays were also performed in presence of JD serum. The serum from shedding cows showed 15% less proliferation. These results indicate that infected cows have a lower systemic capacity to maintain a protective immune response and that, as the disease progresses, an emerging T-helper type-17 immune response is established.

Prolonged gestation in two Holstein cows: transabdominal ultrasonographic findings in late pregnancy and pathologic findings in the fetuses.

Prolonged pregnancy in cattle is a rare condition that is commonly accompanied with fetal adenohypophyseal hypoplasia. The final diagnosis is often challenging as breeding date error remains possible in virtually all situations. In this report, fetal wellbeing assessment is depicted in two Holstein cows suffered from prolonged pregnancy. Transabdominal ultrasonographic findings were compatible with healthy non-stressed fetuses. The clinical and pathologic findings encountered in both fetuses expelled after corticosteroid induction of parturition consisted of adenohypophyseal aplasia and hydronephrosis. Other nervous system anomalies (hydrocephaly or holocephaly) were observed. Tetralogy of Fallot was also found in one calf.

[Disseminated cutaneous and visceral fusariosis in an aplastic patient: an unusual digestive entry]. / Fusariose cutanée et viscérale disséminée chez un malade en aplasie: une porte d'entrée digestive inhabituelle.

INTRODUCTION: The hyalohyphomycetes, Fusarium spp, are very common in our environment. Some of them have been recognized as being opportunistic agents responsible for localized as well as generalized infections, especially in the case of malignant blood diseases. Their poor sensitivity to standard antifungal therapeutics makes them very dangerous. We report a case of cutaneous and systemic fusariosis due to Fusarium moniliforme in a patient with acute lymphoblastic leukemia. CASE-REPORT: A 20 year-old male student was suffering from acute type 6 myeloblastic leukemia. During the second consolidation schedule with a combined therapy of aracytine and amsacrine, this patient whose food diet was exclusively based on cereals, showed evidence of febrile aplasia, associated with myalgia, abdominal pain and diarrhoea. Microbiological samples were sterile. Ten days later, we noted the appearance of painful, diffuse and purple dermohypodermal cutaneous nodules surrounded by an erythematous ring. Histological and microbiological examination of the hypodermis biopsies of the skin nodules revealed invasion by Fusarium moniliforme. Treatment with voriconazole in association with transfusions of leukocytes led to clinical and microbiological cure. DISCUSSION: In our case report, the clinical pattern starting with digestive symptoms suggested dissemination from a digestive site, which is very unusual in Europe. In our patient, the malnutrition, together with a diet exclusively based on contaminated cereals in a context of malignant hemopathy, resulted in the colonization of the digestive tract by these moulds and the aplasia-inducing chemotherapy schedules enhanced their pathogen potential.

[Rhabdomyosarcoma of the thoracic wall in an adult. Apropos of a case]. / Rhabdomyosarcome de la paroi thoracique chez un adulte. A propos d'un cas.

Rhabdomyosarcoma is a malignant tumour generally observed in children or adolescents; thoracic localization is rare. The authors report a case of embryonary rhabdomyosarcoma of the thoracic wall in a 36-year-old subject. Pathology examination of surgical specimens confirmed the diagnosis. Treatment included surgical exeresis together with pre- and post-operative chemotherapy combining doxorubicine (40 mg/m2/cycle), ifosfamide (6 g/m2/cycle) and dacarbazine (900 mg/m2/cycle). Local recurrence, requiring radiotherapy, was observed a few months later and led to the patient's death after a 9-month clinical course.

[Association of IgA linear dermatitis and non-Hodgkin's malignant lymphoma]. / Association d'une dermatose à IgA linéaire et d'un lymphome malin non hodgkinien.

The association between linear IgA dermatosis and neoplasia has been the subject of several publications which suggest that the association is not fortuitous. We report a new case in which a non-Hodgkin's lymphoma was associated with a linear IgA dermatosis and underline the need for full evaluation in search of an associated neoplasia. However, the neoplasia-LAD association is not a true paraneoplastic syndrome since the two pathologies seldom follow a parallel course.

[Acute post-gravidic Budd-Chiari syndrome. One case (author's transl)]. / Syndrome de Budd-Chiari aigu post-gravidique. Une observation.

The sixth case of post-gravidic Budd-Chiari syndrome is reported. In the acute stage of the disease heparin seems to have given immediate favourable results, and the value of long-term heparin treatment is discussed. Post-mortem findings seven years after the acute episode confirmed the evolution towards a certain type of cirrhosis characterized by macroscopically and histologically heterogenous lesions and by persistent liver congestion. Portal hypertension was associated with arterialization of the portal vein and considerable dilatation of the right diaphragmatic veins. The venous drainage of the liver had undergone complex alterations: the supra-hepatic veins were affected with fairly recent incomplete ostial thrombosis, many intra-hepatic veins were reduced to a vestigial reticulum and others were the seat of recent or old re-canalized thrombosis. Cancerous transformation was found to be present in the larger hepatic nodules.