Non-invasive predictors of axillary lymph node burden in breast cancer: a single-institution retrospective analysis.

PURPOSE: Axillary staging is an important prognostic factor in breast cancer. Sentinel lymph node biopsy (SNB) is currently used to stage patients who are clinically and radiologically node-negative. Since the establishment that axillary node clearance (ANC) does not improve overall survival in breast-conserving surgery for patients with low-risk biological cancers, axillary management has become increasingly conservative. This study aims to identify and assess the clinical predictive value of variables that could play a role in the quantification of axillary burden, including the accuracy of quantifying abnormal axillary nodes on ultrasound. METHODS: A retrospective analysis was conducted of hospital data for female breast cancer patients receiving an ANC at our centre between January 2018 and January 2020. The reference standard for axillary burden was surgical histology following SNB and ANC, allowing categorisation of the patients under 'low axillary burden' (2 or fewer pathological macrometastases) or 'high axillary burden' (> 2). After exploratory univariate analysis, multivariate logistic regression was conducted to determine relationships between the outcome category and candidate predictor variables: patient age at diagnosis, tumour focality, tumour size on ultrasound and number of abnormal lymph nodes on axillary ultrasound. RESULTS: One hundred and thirty-five patients were included in the analysis. Logistic regression showed that the number of abnormal lymph nodes on axillary ultrasound was the strongest predictor of axillary burden and statistically significant (P = 0.044), with a sensitivity of 66.7% and specificity of 86.8% (P = 0.011). CONCLUSION: Identifying the number of abnormal lymph nodes on preoperative ultrasound can help to quantify axillary nodal burden and identify patients with high axillary burden, and should be documented as standard in axillary ultrasound reports of patients with breast cancer.

The effects of bit chewing on borborygmi, duodenal motility, and gastrointestinal transit time in clinically normal horses.

OBJECTIVE: To determine the influence of bit chewing on gastrointestinal transit in clinically normal horses. STUDY DESIGN: Prospective crossover designed study. ANIMALS: Six healthy adult horses. METHODS: Horses were assigned randomly to treatment (apple flavored bit) and control (no-bit) groups and studied for 2 × 1-week trial periods with a 2-week washout period between trials. Horses were fasted for 24 h and slowly refed over 3 days. The bit was placed for 20 min every 6 h. Duodenal contractions and borborygmi auscultations were evaluated every 12 h, approximately 5 min following bit placement. Gastrointestinal total transit time (GI TTT) was measured by administering 200 colored beads via stomach tube and then collected in the manure until 50% and 80% were recovered. Measured variables were compared using an ANOVA or Wilcoxon signed-rank test and the P value was noted. RESULTS: The GI TTT was shortened in the bit chewing group (median: 106.37 h, range: 70-171 h) compared to the no-bit group (median: 170.1 h, range: 149-186 h) (P = .0156) at 80% bead passage (only 4/6 horses passed 80%). Borborygmi (P = .8193), duodenal contractions (P = .2605), and 50% bead passage (P = .0781) showed no differences. CONCLUSION: Bit chewing was safe, inexpensive, and well tolerated. Bit chewing shortened GI TTT and might be an adjunct therapy to augment GI TTT. Further clinical studies are warranted. CLINICAL SIGNIFICANCE: Ileus is a common complication following equine abdominal surgery with no current consistently successful treatment. Bit chewing may be a simple and inexpensive way to augment progressive GI motility.

Teaching veterinary surgical skills: Comparison of massed versus spaced instruction.

OBJECTIVE: To determine the effect of massed instruction (MI) versus spaced instruction (SI) of veterinary surgical skills on students' cognitive load and skill retention. STUDY DESIGN: Prospective randomized cohort study STUDY POPULATION: First-year veterinary students from Louisiana State University (LSU; n = 47) and Lincoln Memorial University (LMU; n = 101). METHODS: Students were randomized to MI (two skills in a single session of twice the duration) or SI (one skill per session on two consecutive days). Instructors, instructional ratio, and total educational time was equivalent. Following instruction, students completed a cognitive load questionnaire and underwent a structured assessment immediately after (LMU only), 1 day after, and 3-4 weeks after learning the second skill. Students completed two supervised practice sessions one and 2 weeks after the initial laboratory session(s). RESULTS: Overall cognitive load did not differ between groups (p > .05), although LMUs MI group reported higher physical and time demands, effort, and frustration. At initial assessment, SI students scored higher than MI students for the first skill at both LSU (mean checklist score = 27.7 vs. mean = 24; p = .004) and LMU (mean global rating score = 4.76 vs. mean = 4.55; p = .029). Differences between groups were no longer evident by 3-4 weeks after instruction. CONCLUSION: SI may lead to improved immediate performance; however, supervised practice was sufficient to overcome the initial disparity. CLINICAL SIGNIFICANCE: SI may be beneficial for initial skill performance. However, SI and MI students had similar performance after 3 weeks, suggesting the more convenient curricular design of MI may be sufficient as long as practice sessions are incorporated.

Development of and Validity Evidence for a Canine Ocular Model for Training Novice Veterinary Students to Perform a Fundic Examination.

Indirect fundoscopy is challenging for novice learners, as patients are often intolerant of the procedure, impeding development of proficiency. To address this, we developed a canine ocular simulator that we hypothesized would improve student learning compared to live dogs. Six board-certified veterinary ophthalmologists and 19 second-year veterinary students (novices) performed an indirect fundic examination on the model and live dog. Prior to assessment, novices were introduced to the skill with a standardized teaching protocol and practiced (without feedback) with either the model (n = 10) or live dog (n = 9) for 30 minutes. All participants evaluated realism and usefulness of the model using a Likert-type scale. Performance on the live dog and model was evaluated in all participants using time to completion of task, performance of fundic examination using a checklist and global score, identification of objects in the fundus of the model, and evaluation of time spent looking at the fundus of the model using eye tracking. Novices (trained on simulator or live dogs) were compared in fundic examination performance on the live dog and identification of shapes in the model. In general, experts performed the fundic examination faster (p ≤ .0003) and more proficiently than the novices, although there were no differences in eye tracking behavior between groups (p ≥ .06). No differences were detected between training on simulator versus live dog in development of fundoscopy skills in novices (p ≥ .20). These findings suggest that this canine model may be an effective tool to train students to perform fundoscopy.

Are older people putting themselves at risk when using their walking frames?

BACKGROUND: Walking aids are issued to older adults to prevent falls, however, paradoxically their use has been identified as a risk factor for falling. To prevent falls, walking aids must be used in a stable manner, but it remains unknown to what extent associated clinical guidance is adhered to at home, and whether following guidance facilitates a stable walking pattern. It was the aim of this study to investigate adherence to guidance on walking frame use, and to quantify user stability whilst using walking frames. Additionally, we explored the views of users and healthcare professionals on walking aid use, and regarding the instrumented walking frames ('Smart Walkers') utilized in this study. METHODS: This observational study used Smart Walkers and pressure-sensing insoles to investigate usage patterns of 17 older people in their home environment; corresponding video captured contextual information. Additionally, stability when following, or not, clinical guidance was quantified for a subset of users during walking in an Activities of Daily Living Flat and in a gait laboratory. Two focus groups (users, healthcare professionals) shared their experiences with walking aids and provided feedback on the Smart Walkers. RESULTS: Incorrect use was observed for 16% of single support periods and for 29% of dual support periods, and was associated with environmental constraints and a specific frame design feature. Incorrect use was associated with reduced stability. Participants and healthcare professionals perceived the Smart Walker technology positively. CONCLUSIONS: Clinical guidance cannot easily be adhered to and self-selected strategies reduce stability, hence are placing the user at risk. Current guidance needs to be improved to address environmental constraints whilst facilitating stable walking. The research is highly relevant considering the rising number of walking aid users, their increased falls-risk, and the costs of falls.

Is sentinel node biopsy necessary in the radiologically negative axilla in breast cancer?

PURPOSE: The steady move towards axillary conservatism in breast cancer is based on studies demonstrating that axillary node clearance affords no survival benefit in a subset of patients with a positive pre-operative axillary ultrasound (AUS). However, less attention has been paid to AUS-negative patients who receive sentinel node biopsy as standard. METHODS: Previously assembled systematic review data was reassessed to evaluate nodal burden amongst patients with breast cancer and a clinically and radiologically negative axilla. RESULTS: Pooled data from four cohort studies reporting pre-operative axillary ultrasound in 5139 patients with breast cancer show it has a negative predictive rate of 0.951 (95% confidence interval 0.941-0.960). CONCLUSIONS: Reconsidering the use of ultrasound in patients with early breast cancer and non-palpable axillae reveals that sentinel node biopsy itself may represent surgical over-treatment in patients with a negative axillary ultrasound. The implications of this on the future of surgical management of the axilla are discussed.

Blue dye for identification of sentinel nodes in breast cancer and malignant melanoma: a systematic review and meta-analysis.

The combined technique (radioisotope and blue dye) is the gold standard for sentinel lymph node biopsy (SLNB) and there is wide variation in techniques and blue dyes used. We performed a systematic review and meta-analysis to assess the need for radioisotope and the optimal blue dye for SLNB. A total of 21 studies were included. The SLNB identification rates are high with all the commonly used blue dyes. Furthermore, methylene blue is superior to iso-sulfan blue and Patent Blue V with respect to false-negative rates. The combined technique remains the most accurate and effective technique for SLNB. In order to standardize the SLNB technique, comparative trials to determine the most effective blue dye and national guidelines are required.

Minimally invasive ablative techniques in the treatment of breast cancer: a systematic review and meta-analysis.

PURPOSE: Breast-conserving surgery is effective for breast cancer treatment but is associated with morbidity in particular high re-excision rates. We performed a systematic review and meta-analysis to assess the current evidence for clinical outcomes with minimally invasive ablative techniques in the non-surgical treatment of breast cancer. METHODS: A systematic search of the literature was performed using PubMed and Medline library databases to identify all studies published between 1994 and May 2016. Studies were considered eligible for inclusion if they evaluated the role of ablative techniques in the treatment of breast cancer and included ten patients or more. Studies that failed to fulfil the inclusion criteria were excluded. RESULTS: We identified 63 studies including 1608 patients whose breast tumours were treated with radiofrequency (RFA), high intensity focussed ultrasound (HIFU), cryo-, laser or microwave ablation. Fifty studies reported on the number of patients with complete ablation as found on histopathology and the highest rate of complete ablation was achieved with RFA (87.1%, 491/564) and microwave ablation (83.2%, 89/107). Short-term complications were most often reported with microwave ablation (14.6%, 21/144). Recurrence was reported in 24 patients (4.2%, 24/570) and most often with laser ablation (10.7%, 11/103). The shortest treatment times were observed with RFA (15.6 ± 5.6 min) and the longest with HIFU (101.5 ± 46.6 min). CONCLUSION: Minimally invasive ablative techniques are able to successfully induce coagulative necrosis in breast cancer with a low side effect profile. Adequately powered and prospectively conducted cohort trials are required to confirm complete pathological ablation in all patients.

Magnetic sentinel lymph node biopsy in a murine tumour model.

The magnetic technique for sentinel node biopsy provides a radioisotope-free alternative for staging breast cancer. It requires refinement to reduce "residual iron content" at injection sites by maximising lymphatic uptake to prevent "void artefacts" on magnetic resonance imaging (MRI), which could adversely affect clinical use. The site and timing of injection of magnetic tracer was evaluated in a murine tumour model (right hind limb) in 24 wild type mice. Right-sided intratumoural and left sided subcutaneous injection of magnetic tracer and assessment of nodal iron uptake on MRI, surgical excision and histopathological grading at time frames up to 24 hours were performed. Rapid iron uptake on MRI, smaller "void artefacts"(P<0.001) and a significant increase in iron content with time were identified in the subcutaneous injection group (r=0.937; P<0.001).Subcutaneous injection and increasing delay between tracer injection and surgery is beneficial for lymphatic iron uptake. FROM THE CLINICAL EDITOR: Sentinel lymph node biopsy (SLNB) has been the standard of care in breast cancer management for some time. Recent development has seen the introduction of magnetic tracer for SLNB. In this article, the authors investigated the refined use of magnetic tracer in determining the optimal timing of administration and the location of injection. The findings should provide more data on the future use of this new technique.

Caprine whole blood appears sufficiently stable after 21 days in storage to be suitable for transfusion.

OBJECTIVE: The objective of this study was to determine hematologic changes of stored caprine whole blood in citrate phosphate dextrose adenine solution over a 28-day period. SAMPLE: Ten 250-mL bags of whole blood were collected from 10 female Boer goats from Louisiana State University's Division of Laboratory Animal Medicine herd. METHODS: 10 healthy blood donor goats were selected, and 250 mL of whole blood was drawn from each and stored at 2.78 °C. At the time of collection and every 7 days for a total of 28 days, samples were obtained from the blood bags to determine biochemical and hematologic values of collected blood. Only 5 of the 10 donors had baseline blood bag samples obtained for biochemical evaluation on day 0. At the end of 28 days, the remaining blood was submitted for aerobic and anaerobic culture. RESULTS: Blood values remained within suitable limits for transfusion and below 1% hemolysis for up to 21 days in most samples. Packed cell volume did not change significantly from day 0 to day 28. Lactate significantly increased over the 28 days, though not as dramatically as expected on the basis of other blood storage studies. pH decreased due to anticoagulant acidity but did not drop below 7. Cultures were negative on all blood bags. CLINICAL RELEVANCE: Changes over time are similar to that in other species, and caprine blood appears biochemically and hematologically stable for up to 21 days in storage. In vivo trials are needed for safety and efficacy.

A sensitivity analysis framework for the treatment effect measure used in the meta-analysis of comparative binary data from randomised controlled trials.

The process of undertaking a meta-analysis involves a sequence of decisions, one of which is deciding which measure of treatment effect to use. In particular, for comparative binary data from randomised controlled trials, a wide variety of measures are available such as the odds ratio and the risk difference. It is often of interest to know whether important conclusions would have been substantively different if an alternative measure had been used. Here we develop a new type of sensitivity analysis that incorporates standard measures of treatment effect. Thus, rather than examining the implications of a variety of measures in an ad hoc manner, we can simultaneously examine an entire family of possibilities, including the odds ratio, the arcsine difference and the risk difference.

Prevalence of AO blood group and level of agreement for AO blood-typing methods in pet pigs from Louisiana.

OBJECTIVES: Pet pigs are a species of growing medical interest, and evidence-based practices for blood transfusions are needed. The objectives of this study were to quantify the prevalence of 3 blood group (Bg) phenotypes ("A" and "Aweak " resulting from EAAAA and EAAAO , "0" from EAA00 , or "-" from EAA00 or SSS alleles) in pet pigs and compare results using a human blood-typing card (EldonCard), standard saline agglutination (SSA), and polymerase chain reaction (PCR) sequencing. DESIGN: Cross-sectional study. SETTING: University veterinary teaching hospital. ANIMALS: Ninety-seven pet pigs from Louisiana. INTERVENTIONS: Blood was sampled from randomly selected pet pigs of various breeds, anticoagulated with EDTA, and typed using each investigated test according to the manufacturers' directions or standard laboratory technique. Samples for PCR analysis were stored at -80°C until analysis. Phenotypes were screened via EldonCard. Association between Bg and sex was investigated using chi-square test, with significance at P < 0.05. Kappa (κ) statistic was used to measure the level of agreement between the 3 tests. MEASUREMENTS AND MAIN RESULTS: Pot-bellied pigs represented the majority (84.5%) of this population, with 52 (53.6%) males and 45 (46.4%) females. Genotypic frequencies were 30%, 30%, and 40% for "EAAAA ," "EAAAO ," and "EAA00 ," respectively. Based on EldonCard, 38 phenotypes were classified as "A," 5 as "Aweak ," and 54 as "0" or "-." Results were identical for Bg, with the 3 tested techniques in 90% (45/50) of samples. Agreement between EldonCard and PCR was almost perfect (49/50 [98%], κ = 0.959; P < 0.001). Agreement between SSA and PCR, and EldonCard and SSA was substantial (46/50 [92%], κ = 0.803, P < 0.001 and 93/97 [95.9%], κ = 0.764, P < 0.001, respectively). CONCLUSIONS: The most common blood type was "0" or "-" (55.7%), followed by "A" (39.2%) and "Aweak " (5.1%). There was strong agreement between EldonCard and PCR testing. EldonCard allowed for rapid and reliable phenotype identification ("A," "Aweak ," and "0" or "-") and represents a clinically applicable laboratory method for blood typing in pet pigs.

Reported Use of Second-Language Speech Accommodation in Everyday Interactions: The Role of Individual Differences.

BACKGROUND: Proficient speakers of a language often accommodate less proficient speakers during conversation to facilitate comprehension, but information about factors such as personality and language experience that may shape how speakers perceive accommodation is limited. PURPOSE: We developed an online questionnaire to clarify the use of speech accommodation in relation to individual differences in anxiety, personality, and English proficiency. METHOD: Using Qualtrics Panels for recruitment, we surveyed a representative sample of second-language (L2) English speakers (n = 201) and first-language (L1) English speakers (n = 192) across the United States. We report descriptive results in addition to correlations and a factor analysis to assess the perception of accommodation in L2 and L1 speakers. RESULTS: Only a third of L2 participants reported that L1 speakers change their speech when talking to them, and more than half are frustrated when L1 speakers do not accommodate them. Indeed, a majority of our L1 participants reported that they do not change their speech when talking to L2 speakers. For both groups, measures of anxiety, personality, and L2 proficiency modify results, providing novel evidence on factors that influence L2 accommodation. CONCLUSIONS: Results suggest that L1 speakers accommodate L2 speakers less frequently than previously reported. The data are discussed under communication accommodation theory.

Reduction in transfer of micro-organisms between patients and staff using short-sleeved gowns and hand/arm hygiene in intensive care during the COVID-19 pandemic: A simulation-based randomised trial.

Background: Current personal protective equipment (PPE) practices in UK intensive care units involve "sessional" use of long-sleeved gowns, risking nosocomial infection transmitted via gown sleeves. Data from the first wave of the COVID19 pandemic demonstrated that these changes in infection prevention and control protocols were associated with an increase in healthcare associated bloodstream infections. We therefore explored the use of a protocol using short-sleeved gowns with hand and arm hygiene to reduce this risk. Methods: ICU staff were trained in wearing short-sleeved gowns and using a specific hand and arm washing technique between patients (experimental protocol). They then underwent simulation training, performing COVID-19 intubation and proning tasks using either experimental protocol or the standard (long-sleeved) control protocol. Fluorescent powder was used to simulate microbial contamination, detected using photographs under ultraviolet light. Teams were randomised to use control or experimental PPE first. During the simulation, staff were questioned on their feelings about personal safety, comfort and patient safety. Results: Sixty-eight staff and 17 proning volunteers were studied. Experimental PPE completely prevented staff contamination during COVID-19 intubation, whereas this occurred in 30/67 staff wearing control PPE (p = .003, McNemar). Proning volunteers were contaminated by staff in 15/17 control sessions and in 1/17 with experimental PPE (p = .023 McNemar). Staff comfort was superior with experimental PPE (p< .001, Wilcoxon). Their personal safety perception was initially higher with control PPE, but changed towards neutrality during sessions (p < .001 start, 0.068 end). Their impressions of patient safety were initially similar (p = .87), but finished strongly in favour of experimental PPE (p < .001). Conclusions: Short-sleeved gowns with hand and forearm cleansing appear superior to sessional long-sleeved gowns in preventing cross-contamination between staff and patients.

Pathological Features and Genomic Characterization of an Actinobacillus equuli subsp. equuli Bearing Unique Virulence-Associated Genes from an Adult Horse with Pleuropneumonia.

Actinobacillus equuli subsp. equuli is the etiological agent of sleepy foal disease, an acute form of fatal septicemia in newborn foals. A. equuli is commonly found in the mucous membranes of healthy horses' respiratory and alimentary tracts and rarely causes disease in adult horses. In this study, we report a case of a 22-year-old American Paint gelding presenting clinical signs associated with an atypical pattern of pleuropneumonia subjected to necropsy. The gross and histopathological examinations revealed a unilateral fibrinosuppurative and hemorrhagic pleuropneumonia with an infrequent parenchymal distribution and heavy isolation of A. equuli. The whole genome sequence analysis indicated that the isolate shared 95.9% homology with the only other complete genome of A. equuli subsp. equuli available in GenBank. Seven virulence-associated genes specific to the isolate were identified and categorized as iron acquisition proteins, lipopolysaccharides (LPS), and capsule polysaccharides. Moreover, four genes (glf, wbaP, glycosyltransferase family 2 protein, and apxIB) shared higher amino acid similarity with the invasive Actinobacillus spp. than the reference A. equuli subsp. equuli genome. Availability of the whole genome sequence will allow a better characterization of virulence determinants of A. equuli subsp. equuli, which remain largely elusive.

The Use of Machine Learning to Reduce Overtreatment of the Axilla in Breast Cancer: Retrospective Cohort Study.

BACKGROUND: Patients with early breast cancer undergoing primary surgery, who have low axillary nodal burden, can safely forego axillary node clearance (ANC). However, routine use of axillary ultrasound (AUS) leads to 43% of patients in this group having ANC unnecessarily, following a positive AUS. The intersection of machine learning with medicine can provide innovative ways to understand specific risks within large patient data sets, but this has not yet been trialed in the arena of axillary node management in breast cancer. OBJECTIVE: The objective of this study was to assess if machine learning techniques could be used to improve preoperative identification of patients with low and high axillary metastatic burden. METHODS: A single-center retrospective analysis was performed on patients with breast cancer who had a preoperative AUS, and the specificity and sensitivity of AUS were calculated. Standard statistical methods and machine learning methods, including artificial neural network, naive Bayes, support vector machine, and random forest, were applied to the data to see if they could improve the accuracy of preoperative AUS to better discern high and low axillary burden. RESULTS: The study included 459 patients; 142 (31%) had a positive AUS; among this group, 88 (62%) had 2 or fewer macrometastatic nodes at ANC. Logistic regression outperformed AUS (specificity 0.950 vs 0.809). Of all the methods, the artificial neural network had the highest accuracy (0.919). Interestingly, AUS had the highest sensitivity of all methods (0.777), underlining its utility in this setting. CONCLUSIONS: We demonstrated that machine learning improves identification of the important subgroup of patients with no palpable axillary disease, positive ultrasound, and more than 2 metastatically involved nodes. A negative ultrasound in patients with no palpable lymphadenopathy is highly indicative of low axillary burden, and it is unclear whether sentinel node biopsy adds value in this situation. Further studies with larger patient numbers focusing on specific breast cancer subgroups are required to refine these techniques in this setting.

Increased rates of bone fracture among HIV-infected persons in the HIV Outpatient Study (HOPS) compared with the US general population, 2000-2006.

BACKGROUND: Among persons with HIV infection, low bone mineral density is common and has raised concerns about increased risk of fracture. METHODS: We analyzed data from the HIV Outpatient Study (HOPS), an open prospective cohort study of HIV-infected adults who were followed up at 10 US HIV clinics. We assessed rates of first fractures at any anatomic site during the period 2000-2008. We indirectly standardized the rates of fracture in the HOPS to the general population by age and sex, using data from outpatients in the National Hospital Ambulatory Medical Care Survey (NHAMCS-OPD). We examined factors associated with fractures using Cox proportional hazards modeling. RESULTS: Among 5826 active HOPS patients whose data were analyzed (median baseline age, 40 years; male sex, 79%; white race, 52%; exposure to antiretroviral therapy, 73%), 233 patients had incident fractures (crude annual rates, 59.6-93.5 fractures per 10,000 persons). Age-standardized fracture rates increased from 2000 to 2002 (P = .01) and stabilized thereafter. Among persons aged 25-54 years, both fracture rates and relative proportion of fragility fractures were higher among HOPS patients than among patients in the NHAMCS-OPD. In addition to older age and substance abuse, nadir CD4+ cell count <200 cells/mm(3) (adjusted hazard ratio [aHR], 1.60; 95% confidence interval [CI], 1.11-2.31), hepatitis C infection (aHR, 1.61; 95% CI, 1.13-2.29) and diabetes (aHR, 1.62; 95% CI, 1.00-2.64) were associated with incident fractures. CONCLUSIONS: Age-adjusted fracture rates among HOPS patients were higher than rates in the general US population during the period 2000-2006. Clinicians should regularly assess HIV-infected persons for fracture risk, especially those with low nadir CD4+ cell counts or other established risk factors for fracture.

Axillary dissection versus axillary observation for low risk, clinically node-negative invasive breast cancer: a systematic review and meta-analysis.

PURPOSE: 1. To systematically analyse studies comparing survival outcomes between axillary lymph-node dissection (ALND) and axilla observation (Obs), in women with low-risk, clinically node-negative breast cancer. 2. To consider results in the context of current axillary surgery de-escalation trials and studies. METHODS: 9 eligible studies were identified, 6 RCTs and 3 non-randomized studies (4236 women in total). Outcomes assessed: overall survival (OS) and disease-free survival (DFS). The logged (ln) hazard ratio (HR) was calculated and used as the statistic of interest. Data was grouped by follow-up. RESULTS: Meta-analyses found no significant difference in OS at 5, 10 and 25-years follow-up (5-year ln HR = 0.08, 95% CI - 0.09, 0.25, 10-year ln HR = 0.33, 95% CI - 0.07, 0.72, 25-year ln HR = 0.00, 95% CI - 0.18, 0.19). ALND caused improvement in DFS at 5-years follow-up (ln HR = 0.16, 95% CI 0.03, 0.29), this was not demonstrated at 10 and 25-years follow-up (10-year ln HR = 0.07, 95% CI - 0.09, 0.23, 25-year ln HR = - 0.03, 95% CI - 0.21, 0.16). Studies supporting ALND for DFS at 5-years follow-up had greater relative chemotherapy use in the ALND cohort. CONCLUSION: ALND does not cause a significant improvement in OS in women with clinically node-negative breast cancer. ALND may improve DFS in the short term by tailoring a proportion of patients towards chemotherapy. Our evidence suggests that when the administration of systemic therapy is balanced between the two arms, axillary de-escalation studies will likely find no difference in OS or DFS.

Assessment of Cidofovir for Treatment of Ocular Bovine Herpesvirus-1 Infection in Cattle Using an Ex-Vivo Model.

Bovine herpesvirus-1 (BoHV-1) infection contributes to keratoconjunctivitis, respiratory disease, and reproductive losses in cattle. The objective of this study was to determine the most appropriate ophthalmic antiviral agent for BoHV-1 inhibition using in-vitro culture and novel ex-vivo bovine corneal modeling. Half-maximal inhibitory concentrations of BoHV-1 were determined for cidofovir, ganciclovir, idoxuridine, and trifluridine via in-vitro plaque reduction assays. In-vitro cytotoxicity was compared amongst these compounds via luciferase assays. Trifluridine and cidofovir were the most potent BoHV-1 inhibitors in vitro, while trifluridine and idoxuridine were the most cytotoxic agents. Therefore, cidofovir was the most potent non-cytotoxic agent and was employed in the ex-vivo corneal assay. Corneoscleral rings (n = 36) from fresh cadaver bovine globes were harvested and equally divided into an uninfected, untreated control group; a BoHV-1-infected, untreated group; and a BoHV-1-infected, cidofovir-treated group. Virus isolation for BoHV-1 titers was performed from corneal tissue and liquid media. Histologic measurements of corneal thickness, epithelial cell density, and tissue organization were compared between groups. Substantial BoHV-1 replication was observed in infected, untreated corneas, but BoHV-1 titer was significantly reduced in cidofovir-treated (1.69 ± 0.08 × 103 PFU/mL) versus untreated (8.25 ± 0.25 × 105 PFU/mL, p < 0.0001) tissues by day 2 of culture. No significant differences in histologic criteria were observed between groups. In conclusion, cidofovir warrants further investigation as treatment for BoHV-1 keratoconjunctivitis, with future studies needed to assess in-vivo tolerability and efficacy.

Optimization of SPIO Injection for Sentinel Lymph Node Dissection in a Rat Model.

The magnetic technique, consisting of a magnetic tracer and a handheld magnetometer, is a promising alternative technique for sentinel lymph node dissection (SLND) and was shown to be non-inferior to the standard technique in terms of identification rates. In this study, injection characteristics (iron dose, dilution, time course and massaging) were evaluated to optimize magnetic tracer uptake in the sentinel lymph nodes (SLN) in a rat hindleg model. 202 successful SLNDs were performed. Iron uptake in the SLN is proportional (10% utilization rate) to the injection dose between 20 and 200 µg, showing a plateau uptake of 80 µg in the SLN around 1000 µg injection. Linear regression showed that time had a higher impact than dilution, on the SLN iron uptake. Massaging showed no significant change in iron uptake. The amount of residual iron at the injection site was also proportional to the injection dose without any plateau. Time was a significant factor for wash-out of residual iron. From these results, preoperative injection may be advantageous for SLN detection as well as reduction in residual iron at the injection site by potential decrease in required injection dose.