Breast cancer risk stratification in women of screening age: Incremental effects of adding mammographic density, polygenic risk, and a gene panel.

PURPOSE: There is great promise in breast cancer risk stratification to target screening and prevention. It is unclear whether adding gene panels to other risk tools improves breast cancer risk stratification and adds discriminatory benefit on a population basis. METHODS: In total, 10,025 of 57,902 women aged 46 to 73 years in the Predicting Risk of Cancer at Screening study provided DNA samples. A case-control study was used to evaluate breast cancer risk assessment using polygenic risk scores (PRSs), cancer gene panel (n = 33), mammographic density (density residual [DR]), and risk factors collected using a self-completed 2-page questionnaire (Tyrer-Cuzick [TC] model version 8). In total, 525 cases and 1410 controls underwent gene panel testing and PRS calculation (18, 143, and/or 313 single-nucleotide polymorphisms [SNPs]). RESULTS: Actionable pathogenic variants (PGVs) in BRCA1/2 were found in 1.7% of cases and 0.55% of controls, and overall PGVs were found in 6.1% of cases and 1.3% of controls. A combined assessment of TC8-DR-SNP313 and gene panel provided the best risk stratification with 26.1% of controls and 9.7% of cases identified at <1.4% 10-year risk and 9.01% of controls and 23.3% of cases at ≥8% 10-year risk. Because actionable PGVs were uncommon, discrimination was identical with/without gene panel (with/without: area under the curve = 0.67, 95% CI = 0.64-0.70). Only 7 of 17 PGVs in cases resulted in actionable risk category change. Extended case (n = 644)-control (n = 1779) series with TC8-DR-SNP143 identified 18.9% of controls and only 6.4% of stage 2+ cases at <1.4% 10-year risk and 20.7% of controls and 47.9% of stage 2+ cases at ≥5% 10-year risk. CONCLUSION: Further studies and economic analysis will determine whether adding panels to PRS is a cost-effective strategy for risk stratification.

A systematic review of speech, language and communication interventions for children with Down syndrome from 0 to 6 years.

BACKGROUND: Speech and language acquisition can be a challenge for young children with Down syndrome (DS), and while early intervention is important, we do not know what early interventions exist and how effective they may be. AIMS: To systematically review existing early speech, language and communication interventions for young children with DS from birth up to 6 years, and to investigate their effectiveness in improving speech, language and communication outcomes in children with DS. Other outcomes are changes in parental behaviour and their responsiveness METHODS & PROCEDURES: We conducted a systematic search of relevant electronic databases to identify early intervention studies targeting speech, language and communication outcomes in children with DS published up to May 2020. A total of 11 studies that met the inclusion criteria were synthesized and appraised for quality using the PEDro-P scale. There were a total of 242 children. We identified three types of intervention: communication training and responsive teaching, early stimulation programme, and dialectic-didactic approach. MAIN CONTRIBUTION: The findings from nine out of the 11 studies reported positive outcomes for children's language and communication up to 18 months following the intervention. All nine studies reported interventions that were co-delivered by parents and clinicians. However, there was also a de-accelerated growth in requesting behaviours in the intervention group reported by one study as well as a case of no improvement for the intervention group. Three studies provided some evidence of improvements to parent outcomes, such as increased parental language input and increased responsiveness. However, there was a moderate to high risk of bias for all studies included. CONCLUSIONS: The findings from this review suggest that interventions that have high dosage, focus on language and communication training within a naturalistic setting, and are co-delivered by parents and clinicians/researchers may have the potential to provide positive outcomes for children with DS between 0 and 6 years of age. Due to the limited number of studies, limited heterogeneous data and the moderate to high risk of bias across studies, there is an urgent need for higher quality intervention studies in the field to build the evidence base. WHAT THIS PAPER ADDS: What is already known on the subject Speech and language acquisition is usually delayed in children with DS, yet there are currently no standard interventions for children under 6. A number of research-based interventions exist in the literature, yet it is unknown how effective these are. What this study adds to existing knowledge This is the first systematic review that specifically and exclusively focuses on parent- and non-parent-mediated speech, language and communication interventions for children with DS between 0 and 6 years of age. It complements three existing recent reviews, each of which has a slightly different focus. The previously published reviews have covered only parent-mediated interventions, excluding interventions not mediated by parents, have reviewed interventions including children and adults, without any mention of what early interventions may be like or how effective these may be for young children with DS, have not always assessed risk of bias or have focused specifically on language interventions excluding those focusing on speech articulation or pre-linguistic skills. The findings from the current review suggest that interventions that have high dosage focus on language and communication training within a naturalistic setting and are co-delivered by parents and clinicians/researchers may have the potential to provide positive outcomes for children with Diwn syndrome from 0 to 6. We acknowledge that the current evidence base comes from studies with moderate to high risk of bias, hence our conclusions are not definitive. What are the potential or actual clinical implications of this work? Speech and language therapists will have synthesized information and a quick reference point on what type of interventions exist for children with DS under the age of 6, and evidence of which intervention approaches may be promising in terms of providing positive outcomes. However, it is acknowledged that, due to the limited number of studies and the moderate to high risk of bias inherent in the evidence, there is an urgent need for higher quality intervention studies in the field to build the evidence base.

Suspensory ligament size does not change after plantar fasciotomy and neurectomy of the deep branch of the lateral plantar nerve by ultrasonographic assessment.

OBJECTIVE: To determine the short-term effect of plantar fasciotomy and neurectomy (PFN) of the deep branch of the lateral plantar nerve on the proximal suspensory ligament (PSL) cross-sectional area (CSA) in horses with hindlimb proximal suspensory desmopathy (PSD). STUDY DESIGN: Analytical, observational, cohort study. SAMPLE POPULATION: Twenty-one horses. METHODS: Records of horses with chronic PSD treated by PFN were included if a preoperative ultrasonographic examination was available and at least one postoperative ultrasonographic examination. One masked observer measured the ultrasonographic cross-sectional area (CSA) of the PSL. Intraobserver reliability was determined by repeatedly measuring a subset of ultrasonographic images (n = 127). Two masked observers measured the cross-sectional area of the proximal suspensory ligament (PSL-CSA) on preoperative proton density (PD)-weighted transverse high field magnetic resonance images (n = 19 horses) . Agreements for PSL-CSA between preoperative ultrasonographic and MRI measures and between the two magnetic resonance imaging (MRI) observers were assessed. Follow up considered the horses' ability to return to exercise and their owners' satisfaction. RESULTS: The reliability of the ultrasonographic measurement of the PSL-CSA was excellent. Agreement between ultrasonographic assessment and MRI assessment of PSL-CSA was good. No difference was detected between preoperative (median, interquartile range; oblique-incidence, 2.07, 1.72-2.55; on-incidence, 2.23, 1.98-2.65) and postoperative (oblique-incidence, 2.08, 1.80-2.74; on-incidence, 2.28, 2.01-2.74) PSL-CSAs. At a median of 12 months (4-33 months), 16/20 (80%) owners reported the horse was "better" and 15/20 (75%) functioned at or above preoperative levels. CONCLUSION: Ultrasonographic measurement of the PSL-CSA was reproducible and in good agreement with MRI measurement. The PSL-CSA was not influenced by PFN. CLINICAL SIGNIFICANCE: The PSL-CSA cannot be used to guide return to function.

Ultrasound-assisted injection of the centrodistal joint in the horse.

BACKGROUND: Injection of the centrodistal (CD) joint in the horse is a commonly performed procedure for both diagnostic and therapeutic purposes. This procedure can be technically challenging, and while radiographic guidance has been previously used, ultrasound localised injection of the CD joint has not been described. OBJECTIVES: The purpose of this study was to explore the feasibility of using ultrasound localisation to increase the accuracy of CD joint injection. STUDY DESIGN: Experimental method assessment. METHODS: One operator performed the ultrasound and injection of 24 CD joints in 12 sedated horses. The joints were injected with iohexol (2 ml), sterile saline (1.5 ml) and amikacin (0.5 ml). Dorsoplantar and dorsomedial plantarolateral radiographic projections were obtained immediately after injection to evaluate the presence of contrast material in the CD joint. RESULTS: The CD joint was successfully injected in 17/24 joints, representing a 70.8% accuracy. MAIN LIMITATIONS: The horses used in this study were from the University research herd, and not clinical cases. One investigator performed all the ultrasonography and CD joint injections. CONCLUSIONS: The use of ultrasound localisation could improve success of CD joint injection as well as improve the learning curve of less experienced practitioners learning this procedure.

What are the benefits and harms of risk stratified screening as part of the NHS breast screening Programme? Study protocol for a multi-site non-randomised comparison of BC-predict versus usual screening (NCT04359420).

BACKGROUND: In principle, risk-stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) should produce a better balance of benefits and harms. The main benefit is the offer of NICE-approved more frequent screening and/ or chemoprevention for women who are at increased risk, but are unaware of this. We have developed BC-Predict, to be offered to women when invited to NHSBSP which collects information on risk factors (self-reported information on family history and hormone-related factors via questionnaire; mammographic density; and in a sub-sample, Single Nucleotide Polymorphisms). BC-Predict produces risk feedback letters, inviting women at high risk (≥8% 10-year) or moderate risk (≥5 to < 8% 10-year) to have discussion of prevention and early detection options at Family History, Risk and Prevention Clinics. Despite the promise of systems such as BC-Predict, there are still too many uncertainties for a fully-powered definitive trial to be appropriate or ethical. The present research aims to identify these key uncertainties regarding the feasibility of integrating BC-Predict into the NHSBSP. Key objectives of the present research are to quantify important potential benefits and harms, and identify key drivers of the relative cost-effectiveness of embedding BC-Predict into NHSBSP. METHODS: A non-randomised fully counterbalanced study design will be used, to include approximately equal numbers of women offered NHSBSP (n = 18,700) and BC-Predict (n = 18,700) from selected screening sites (n = 7). In the initial 8-month time period, women eligible for NHSBSP will be offered BC-Predict in four screening sites. Three screening sites will offer women usual NHSBSP. In the following 8-months the study sites offering usual NHSBSP switch to BC-Predict and vice versa. Key potential benefits including uptake of risk consultations, chemoprevention and additional screening will be obtained for both groups. Key potential harms such as increased anxiety will be obtained via self-report questionnaires, with embedded qualitative process analysis. A decision-analytic model-based cost-effectiveness analysis will identify the key uncertainties underpinning the relative cost-effectiveness of embedding BC-Predict into NHSBSP. DISCUSSION: We will assess the feasibility of integrating BC-Predict into the NHSBSP, and identify the main uncertainties for a definitive evaluation of the clinical and cost-effectiveness of BC-Predict. TRIAL REGISTRATION: Retrospectively registered with clinicaltrials.gov (NCT04359420).

A case-control evaluation of 143 single nucleotide polymorphisms for breast cancer risk stratification with classical factors and mammographic density.

Panels of single nucleotide polymorphisms (SNPs) stratify risk for breast cancer in women from the general population, but studies are needed assess their use in a fully comprehensive model including classical risk factors, mammographic density and more than 100 SNPs associated with breast cancer. A case-control study was designed (1,668 controls, 405 cases) in women aged 47-73 years attending routine screening in Manchester UK, and enrolled in a wider study to assess methods for risk assessment. Risk from classical questionnaire risk factors was assessed using the Tyrer-Cuzick model; mean percentage visual mammographic density was scored by two independent readers. DNA extracted from saliva was genotyped at selected SNPs using the OncoArray. A predefined polygenic risk score based on 143 SNPs was calculated (SNP143). The odds ratio (OR, and 95% confidence interval, CI) per interquartile range (IQ-OR) of SNP143 was estimated unadjusted and adjusted for Tyrer-Cuzick and breast density. Secondary analysis assessed risk by oestrogen receptor (ER) status. The primary polygenic risk score was well calibrated (O/E OR 1.10, 95% CI 0.86-1.34) and accuracy was retained after adjustment for Tyrer-Cuzick risk and mammographic density (IQ-OR unadjusted 2.12, 95% CI% 1.75-2.42; adjusted 2.06, 95% CI 1.75-2.42). SNP143 was a risk factor for ER+ and ER- breast cancer (adjusted IQ-OR, ER+ 2.11, 95% CI 1.78-2.51; ER- 1.81, 95% CI 1.16-2.84). In conclusion, polygenic risk scores based on a large number of SNPs improve risk stratification in combination with classical risk factors and mammographic density, and SNP143 was similarly predictive for ER-positive and ER-negative disease.

Breast cancer pathology and stage are better predicted by risk stratification models that include mammographic density and common genetic variants.

PURPOSE: To improve breast cancer risk stratification to enable more targeted early detection/prevention strategies that will better balance risks and benefits of population screening programmes. METHODS: 9362 of 57,902 women in the Predicting-Risk-Of-Cancer-At-Screening (PROCAS) study who were unaffected by breast cancer at study entry and provided DNA for a polygenic risk score (PRS). The PRS was analysed alongside mammographic density (density-residual-DR) and standard risk factors (Tyrer-Cuzick-model) to assess future risk of breast cancer based on tumour stage receptor expression and pathology. RESULTS: 195 prospective incident breast cancers had a prediction based on TC/DR/PRS which was informative for subsequent breast cancer overall [IQ-OR 2.25 (95% CI 1.89-2.68)] with excellent calibration-(0.99). The model performed particularly well in predicting higher stage stage 2+ IQ-OR 2.69 (95% CI 2.02-3.60) and ER + BCs (IQ-OR 2.36 (95% CI 1.93-2.89)). DR was most predictive for HER2+ and stage 2+ cancers but did not discriminate as well between poor and extremely good prognosis BC as either Tyrer-Cuzick or PRS. In contrast, PRS gave the highest OR for incident stage 2+ cancers, [IQR-OR 1.79 (95% CI 1.30-2.46)]. CONCLUSIONS: A combined approach using Tyrer-Cuzick/DR/PRS provides accurate risk stratification, particularly for poor prognosis cancers. This provides support for reducing the screening interval in high-risk women and increasing the screening interval in low-risk women defined by this model.

Psychological impact of providing women with personalised 10-year breast cancer risk estimates.

BACKGROUND: The Predicting Risk of Cancer at Screening (PROCAS) study estimated 10-year breast cancer risk for 53,596 women attending NHS Breast Screening Programme. The present study, nested within the PROCAS study, aimed to assess the psychological impact of receiving breast cancer risk estimates, based on: (a) the Tyrer-Cuzick (T-C) algorithm including breast density or (b) T-C including breast density plus single-nucleotide polymorphisms (SNPs), versus (c) comparison women awaiting results. METHODS: A sample of 2138 women from the PROCAS study was stratified by testing groups: T-C only, T-C(+SNPs) and comparison women; and by 10-year risk estimates received: 'moderate' (5-7.99%), 'average' (2-4.99%) or 'below average' (<1.99%) risk. Postal questionnaires were returned by 765 (36%) women. RESULTS: Overall state anxiety and cancer worry were low, and similar for women in T-C only and T-C(+SNPs) groups. Women in both T-C only and T-C(+SNPs) groups showed lower-state anxiety but slightly higher cancer worry than comparison women awaiting results. Risk information had no consistent effects on intentions to change behaviour. Most women were satisfied with information provided. There was considerable variation in understanding. CONCLUSIONS: No major harms of providing women with 10-year breast cancer risk estimates were detected. Research to establish the feasibility of risk-stratified breast screening is warranted.

Breast cancer risk in a screening cohort of Asian and white British/Irish women from Manchester UK.

BACKGROUND: The differences between breast cancer risk factors in white British/Irish and Asian women attending screening in the UK are not well documented. METHODS: Between 2009-15 ethnicity and traditional breast cancer risk factors were self-identified by a screening cohort from Greater Manchester, with follow up to 2016. Risk factors and incidence rates were compared using age-standardised statistics (European standard population). RESULTS: Eight hundred and seventy-nine Asian women and 51,779 unaffected white British/Irish women aged 46-73 years were recruited. Asian women were at lower predicted breast cancer risk from hormonal and reproductive risk factors than white British/Irish women (mean 10 year risk 2.6% vs 3.1%, difference 0.4%, 95%CI 0.3-0.5%). White British/Irish women were more likely to have had a younger age at menarche, be overweight or obese, taller, used hormone replacement therapy and not to have had children.. However, despite being less overweight Asian women had gained more weight from age 20 years and were less likely to undertake moderate physical activity. Asian women also had a slightly higher mammographic density. Asian age-standardised incidence was 3.2 (95%CI 1.6-5.2, 18 cancers) per thousand women/year vs 4.5 (95%CI 4.2-4.8, 1076 cancers) for white British/Irish women. CONCLUSIONS: Asian women attending screening in Greater Manchester are likely to have a lower risk of breast cancer than white British/Irish women, but they undertake less physical activity and have more adult weight gain.

Use of Single-Nucleotide Polymorphisms and Mammographic Density Plus Classic Risk Factors for Breast Cancer Risk Prediction.

IMPORTANCE: Single-nucleotide polymorphisms (SNPs) have demonstrated an association with breast cancer susceptibility, but there is limited evidence on how to incorporate them into current breast cancer risk prediction models. OBJECTIVE: To determine whether a panel of 18 SNPs (SNP18) may be used to predict breast cancer in combination with classic risk factors and mammographic density. DESIGN, SETTING, AND PARTICIPANTS: This cohort study enrolled a subcohort of 9363 women, aged 46 to 73 years, without a previous breast cancer diagnosis from the larger prospective cohort of the PROCAS study (Predicting Risk of Cancer at Screening) specifically to evaluate breast cancer risk-assessment methods. Enrollment took place from October 2009 through June 2015 from multiple population-based screening centers in Greater Manchester, England. Follow-up continued through January 5, 2017. EXPOSURES: Genotyping of 18 SNPs, visual-assessment percentage mammographic density, and classic risk assessed by the Tyrer-Cuzick risk model from a self-completed questionnaire at cohort entry. MAIN OUTCOMES AND MEASURES: The predictive ability of SNP18 for breast cancer diagnosis (invasive and ductal carcinoma in situ) was assessed using logistic regression odds ratios per interquartile range of the predicted risk. RESULTS: A total of 9363 women were enrolled in this study (mean [range] age, 59 [46-73] years). Of these, 466 were found to have breast cancer (271 prevalent; 195 incident). SNP18 was similarly predictive when unadjusted or adjusted for mammographic density and classic factors (odds ratios per interquartile range, respectively, 1.56; 95% CI, 1.38-1.77 and 1.53; 95% CI, 1.35-1.74), with observed risks being very close to expected (adjusted observed-to-expected odds ratio, 0.98; 95% CI, 0.69-1.28). A combined risk assessment indicated 18% of the subcohort to be at 5% or greater 10-year risk, compared with 30% of all cancers, 35% of interval-detected cancers, and 42% of stage 2+ cancers. In contrast, 33% of the subcohort were at less than 2% risk but accounted for only 18%, 17%, and 15% of the total, interval, and stage 2+ breast cancers, respectively. CONCLUSIONS AND RELEVANCE: SNP18 added substantial information to risk assessment based on the Tyrer-Cuzick model and mammographic density. A combined risk is likely to aid risk-stratified screening and prevention strategies.

Evaluation of a New Surgical Treatment for Equine Hind Limb Proximal Suspensory Desmitis.

OBJECTIVE: To evaluate the effects of a new microfracture and ligament splitting procedure on ligament healing and to examine the usefulness of magnetic resonance (MR) imaging for monitoring ligament healing over time using a collagenase model of hind limb proximal suspensory desmitis. STUDY DESIGN: Experimental in vivo study. ANIMALS: Healthy adult horses (n=6). METHODS: Horses were free of lameness with normal hind limb proximal suspensory ligaments (PSL). The origin of both hind limb PSL was injected with collagenase and underwent MR imaging 2 weeks later, followed by the microfracture and ligament splitting procedure on 1 limb, with the opposite limb serving as the sham-operated control. Serial lameness and MR examinations were performed. Horses were euthanatized 210 days after surgery, the PSL harvested, and histology, biochemistry, and gene expression performed on both PSL. RESULTS: Collagenase lesions viewed on MR images appeared similar to those seen clinically. Serial MR images demonstrated resolution of abnormal signal intensity and tissue formation in the microfracture sites within the third metatarsal bone. Treated limbs had histologic evidence of connective tissue appearing to originate from the small perforations and blending into the ligament but no statistical differences were identified. Gene expression for cartilage oligomeric matrix protein and decorin were significantly increased in treated compared to control limbs. CONCLUSION: The microfracture and ligament splitting procedure did incite a tissue response but further clinical investigation is necessary to determine if this tissue remodeling at the bone-ligament interface translates to improved clinical outcome. MR imaging may be useful to follow healing in horses with hind limb proximal suspensory desmitis.

Mammographic density adds accuracy to both the Tyrer-Cuzick and Gail breast cancer risk models in a prospective UK screening cohort.

INTRODUCTION: The Predicting Risk of Cancer at Screening study in Manchester, UK, is a prospective study of breast cancer risk estimation. It was designed to assess whether mammographic density may help in refinement of breast cancer risk estimation using either the Gail model (Breast Cancer Risk Assessment Tool) or the Tyrer-Cuzick model (International Breast Intervention Study model). METHODS: Mammographic density was measured at entry as a percentage visual assessment, adjusted for age and body mass index. Tyrer-Cuzick and Gail 10-year risks were based on a questionnaire completed contemporaneously. Breast cancers were identified at the entry screen or shortly thereafter. The contribution of density to risk models was assessed using odds ratios (ORs) with profile likelihood confidence intervals (CIs) and area under the receiver operating characteristic curve (AUC). The calibration of predicted ORs was estimated as a percentage [(observed vs expected (O/E)] from logistic regression. RESULTS: The analysis included 50,628 women aged 47-73 years who were recruited between October 2009 and September 2013. Of these, 697 had breast cancer diagnosed after enrolment. Median follow-up was 3.2 years. Breast density [interquartile range odds ratio (IQR-OR) 1.48, 95 % CI 1.34-1.63, AUC 0.59] was a slightly stronger univariate risk factor than the Tyrer-Cuzick model [IQR-OR 1.36 (95 % CI 1.25-1.48), O/E 60 % (95 % CI 44-74), AUC 0.57] or the Gail model [IQR-OR 1.22 (95 % CI 1.12-1.33), O/E 46 % (95 % CI 26-65 %), AUC 0.55]. It continued to add information after allowing for Tyrer-Cuzick [IQR-OR 1.47 (95 % CI 1.33-1.62), combined AUC 0.61] or Gail [IQR-OR 1.45 (95 % CI 1.32-1.60), combined AUC 0.59]. CONCLUSIONS: Breast density may be usefully combined with the Tyrer-Cuzick model or the Gail model.

Medical treatment of horses with deep digital flexor tendon injuries diagnosed with high-field-strength magnetic resonance imaging: 118 cases (2000-2010).

OBJECTIVE: To describe the location and severity of deep digital flexor tendon (DDFT) lesions diagnosed by means of high-field-strength MRI in horses and to identify variables associated with return to activity following medical treatment. DESIGN: Retrospective case series. ANIMALS: 118 horses. PROCEDURES: Medical records of horses with DDFT injury diagnosed with MRI over a 10-year period (2000-2010) and treated medically (intrasynovial administration of corticosteroids and sodium hyaluronan, rest and rehabilitation, or both) were reviewed. History, signalment, use, results of lameness examination and diagnostic local anesthesia, MRI findings, and treatment details were recorded. Outcome was obtained by telephone interview or follow-up examination. Horses were grouped by predictor variables and analyzed with logistic regression to identify significant effects. RESULTS: Overall, of 97 horses available for follow-up (median time to follow-up, 5 years; range, 1 to 12 years), 59 (61%) returned to activity for a mean duration of 22.6 months (median, 18 months; range, 3 to 72 months), with 25 (26%) still sound at follow-up. Of horses with mild, moderate, and severe injury, 21 of 29 (72%), 20 of 36 (56%), and 18 of 32 (56%), respectively, returned to use. Horses treated with intrasynovial corticosteroid injection and 6 months of rest and rehabilitation returned to use for a significantly longer duration than did horses treated without rest. Western performance horses returned to use for a significantly longer duration than did English performance horses. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study suggested that outcome for horses with DDFT injuries treated medically depended on injury severity, presence of concurrent injury to other structures in the foot, type of activity, and owner compliance with specific treatment recommendations. Although some horses successfully returned to prior activity, additional treatment options are needed to improve outcome in horses with severe injuries and to improve long-term prognosis.

Tumour characteristics and survival in familial breast cancer prospectively diagnosed by annual mammography.

Women from breast cancer families without a demonstrable BRCA1/2 mutation were subjected to annual mammography from age 30 years onwards. One-hundred and ninety-eight patients were diagnosed prospectively with invasive breast cancer and followed for a total of 1513 years. Overall 10-year survival was 88 %. Together with our previous report that women in such kindreds had about twice the population risk of breast cancer, the combined conclusion was that the overall chances of developing breast cancer causing death within 10 years before 50 years of age was 1 % or less when subjected to annual mammography and current treatment. These are empirical prospective observations which may be used for genetic counselling. The majority (160/194 = 84 %) of patients had ER+ and/or low grade tumours with 92 % 10-year survival. One minor group of the patients had ER- tumours, another small group had high grade tumours with nodal spread, both groups were associated with worse prognosis, but the two groups were not mutually associated.

Comparison of limited-contact dynamic compression plate and locking compression plate constructs for proximal interphalangeal joint arthrodesis in the horse.

This study compared in vitro monotonic and cyclic mechanical properties of equine proximal interphalangeal joint arthrodeses stabilized using an open or closed technique combined with axial 4.5 mm narrow limited-contact dynamic compression plate (LC-DCP) or 4.5 mm narrow locking compression plate (LCP). Ten forelimb pairs were randomly assigned to LCP or LC-DCP groups. One limb in each pair was assigned to either open or closed technique. Limbs were tested for cyclic fatigue at 20 000 cycles and then single-cycle to failure under 3-point dorsopalmar bending. There was no significant difference in stiffness of constructs during cyclic fatigue testing or on force or stiffness at failure in single cycle to failure testing between open and closed techniques or between plate types. Both implants, surgical technique, or combinations thereof are suitable for clinical use. More work is necessary to define the interaction between implant type and surgical technique.

Comparaison des constructions de plaques de compression dynamique à contact limité et de plaques de compression à verrouillage pour l'arthrodèse de l'articulation interphalangienne proximale chez les chevaux. Cette étude a comparé les propriétés mécaniques monotoniques et cycliques in vitro des arthrodèses interphalangiennes proximales équines stabilisées à l'aide d'une technique ouverte ou fermée combinée à une plaque de compression dynamique axiale étroite à contact limité de 4,5 mm (LC-DCP) ou à une plaque de compression étroite à verrouillage de 4,5 mm (LCP). Dix paires de pattes avant ont été assignées au hasard à des groupes LCP ou LC-DCP. Une patte de chaque paire était assignée soit à la technique ouverte ou fermée. Les pattes ont été évaluées pour la fatigue cyclique à 20 000 cycles, puis à un cycle unique jusqu'à l'échec à l'aide d'une flexion dorsopalmaire à 3 points. Il n'y avait pas de différence significative dans la rigidité des constructions durant l'évaluation de fatigue cyclique ou sur la force ou la rigidité à l'échec durant l'évaluation dans un cycle unique jusqu'à l'échec entre les techniques ouvertes et fermées ou entre les types de plaques. Les deux implants, techniques chirurgicales ou une combinaison des deux sont appropriés à l'usage clinique. Il est nécessaire d'effectuer des recherches additionnelles pour définir l'interaction entre le type d'implant et la technique chirurgicale.(Traduit par Isabelle Vallières).

Comparison of basilar and axial sesamoidean approaches for digital flexor tendon sheath synoviocentesis and injection in horses.

OBJECTIVE: To define a method for the basilar sesamoidean approach (BSA) to the digital flexor tendon sheath (DFTS) in horses and compare it with the axial sesamoidean approach (ASA) for DFTS synoviocentesis and injection. DESIGN: Evaluation study. ANIMALS: 12 healthy adult mares without evidence of abnormalities related to the lower limbs. PROCEDURES: Each horse had 1 forelimb and 1 hind limb assigned to each DFTS approach (basilar vs axial, relative to the proximal sesamoid bones) in a Latin square design. The order of horses and of limb injection for each horse was randomly selected. All procedures were performed in standing sedated horses. The number of attempts to place a needle in the DFTS, presence of synovial fluid in the needle hub, time for DFTS injection, and number of accurate injections of sterile contrast material into the DFTS (evaluated by means of radiography) were compared between methods. RESULTS: Median time for injection was significantly shorter for the BSA, compared with the ASA. The median number of times the needle was redirected was also significantly less for the BSA. Odds of obtaining synovial fluid via the BSA were 5.7 times as great as for the ASA (95% confidence interval, 1.2 to 278). Successful injection of contrast material into the DFTS did not differ significantly between the BSA (24/24 limbs) and ASA (23/24). CONCLUSIONS AND CLINICAL RELEVANCE: The BSA was a useful method for DFTS synoviocentesis in the forelimbs and hind limbs of standing sedated horses and was superior to the ASA in most aspects. This approach to the DFTS should be considered when DFTS injection or synovial fluid retrieval is desired, particularly in horses with minimal DFTS effusion.

MRI findings in 232 horses with lameness localized to the metacarpo(tarso)phalangeal region and without a radiographic diagnosis.

Two hundred and thirty-two horses with lameness localized to the metacarpo(tarso)phalangeal (MCP/MTP) region without a radiographic diagnosis were evaluated. All horses had high-field magnetic resonance (MR) imaging of the MCP/MTP region performed for the lame limb and the contralateral limb for comparison. There were 46 horses that had bilateral abnormalities in the forelimbs; 27 of these horses were not lame in the contralateral limb at the time of examination. Bilateral hind limb abnormalities were observed in 37 horses; 22 horses were not lame in the contralateral limb. Soft tissue abnormalities alone were observed in 218 limbs (162 horses). Subchondral bone and articular cartilage abnormalities alone were observed in 43 limbs (34 horses). A combination of soft tissue, subchondral bone, and cartilage abnormalities were observed in 64 limbs (36 horses). The distribution of primary abnormalities was as follows; oblique distal sesamoidean ligament desmitis (73 limbs in 56 horses), straight distal sesamoidean ligament desmitis (44 limbs in 38 horses), chronic subchondral bone injuries (15 limbs in 12 horses), suspensory ligament branch desmitis (14 limbs in 12 horses), collateral ligament desmitis (12 limbs in 12 horses), tendonitis of the superficial and deep digital flexor tendons (10 limbs in 10 horses), osteochondral defects greater than 1 cm (nine limbs in six horses), osteochondral defects less than 1 cm (eight limbs in seven horses), bone marrow lesions (six limbs in five horses), intersesamoidean ligament desmitis (five limbs in four horses). MR imaging is useful in diagnosing bone and soft tissue injuries when radiographs and ultrasound fail to yield a diagnosis.

Response to injection of the navicular bursa with corticosteroid and hyaluronan following high-field magnetic resonance imaging in horses with signs of navicular syndrome: 101 cases (2000-2008).

OBJECTIVE: To determine treatment outcome on the basis of pathological changes identified on MRI and lameness duration in horses with navicular syndrome that underwent injection of corticosteroid and hyaluronan into the navicular bursa. DESIGN: Retrospective case series. ANIMALS: 101 horses with navicular syndrome. PROCEDURES: Medical records of horses with signs of navicular syndrome evaluated between January 2000 and December 2008 were reviewed. Data on signalment, use of the horse, history, affected limbs, duration of lameness, findings on lameness examination, radiographic findings, MRI findings, treatment, and outcome were collected from the medical records. Follow-up information was obtained a minimum of 10 months after navicular bursa injection. RESULTS: Following navicular bursa injection, 76 of 101 (75%) horses returned to their intended use for a mean of 9.66 months, and 35 (35%) were sound at follow-up. Horses that had been lame for < 6 months before treatment were significantly more likely to return to their intended use, have a longer positive response to treatment, and be sound at follow-up, compared with horses that had a longer lameness history. Horses with primary deep digital flexor (DDF) tendonitis responded best to navicular bursa injection with rest and rehabilitation, followed by horses with navicular bursitis and horses with DDF tendonitis and adhesions to the collateral sesamoidean ligament of the distal sesamoid (navicular) bone. Horses with scar tissue in the proximal portion of the navicular bursa, adhesions from the navicular bone to the DDF tendon, or multiple abnormalities did not respond as well to treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Response to navicular bursa injection with corticosteroid and hyaluronan in horses with navicular syndrome was dependent on the disease process detected on MRI and duration of lameness.

Desmotomy of the accessory ligament of the deep digital flexor tendon in the forelimb of 24 horses 2 years and older.

OBJECTIVE: To report outcome after desmotomy of the accessory ligament of the deep digital flexor tendon (ALDDFT) in adult horses (≥2 years) for treatment of desmitis of the ALDDFT or flexural deformity of the distal interphalangeal joint (FDDIJ). STUDY DESIGN: Case series. ANIMALS: Horses with desmitis of the ALDDFT (n=9) and FDDIJ (n=15). METHODS: Records (April 1996-July 2008) of 24 adult horses (mean age, 6.7 years) that had ALDDFT desmotomy were reviewed. Follow-up data was obtained 12-120 months after desmotomy. RESULTS: Outcome was available for 22 horses; 18 (82%; 6 of 8 horses with desmitis of the ALDDFT and 12 of 14 with FDDIJ) returned to their intended use within 6-24 months (mean, 12 months). CONCLUSION: In mature horses, ALDDFT desmotomy resulted in successful return to intended use in most horses with ALDDFT desmitis (75%) or FDDIJ (86%).

Evaluation of an arthroscopic approach for transection of the equine collateral sesamoidean ligament.

OBJECTIVE: To evaluate: (1) an arthroscopic technique for transection of the collateral sesamoidean ligament (CSL); and (2) the healing response using magnetic resonance (MR) and microscopic examination. STUDY DESIGN: Experimental study. ANIMALS: Adult horses (n=6). METHODS: Six sound horses with normal front foot radiographic and MR examinations were used. Lameness examination was performed before surgery and monthly for 12 months. Front foot radiography was performed at 180 and 360 days after surgery. Front foot MR was performed before, and at 7, 90, 180, and 360 days after surgery. Arthroscopic CSL desmotomy was performed on 1 forelimb. Gross and microscopic examination was performed on the CSL from both forelimbs at 360 days after surgery. Lameness scores were compared over time using the nonparametric Friedman's test for paired groups. CSL measurements were compared using paired t-tests with a 2-tailed significance level of P<.05. RESULTS: Radiographs remained normal throughout study period. Surgery resulted in lameness on the operated limb for up to 2 months, after which all horses returned to soundness. CSL transection was confirmed during arthroscopy and with MR examination 7 days after surgery. Gross and microscopic evaluation confirmed ligament healing. CONCLUSIONS: CSL desmotomy resulted in short-term lameness after surgery followed by healing of the CSL confirmed by gross and microscopic analysis.