Improved Outcome With Knee Arthroscopy Relative to Physiotherapy for Symptomatic Unstable Meniscal Tears: 2-Year Prospective Cohort Study.

BACKGROUND: Although preservation of meniscal tissue is paramount, there are occasions when repair of a torn meniscus is not possible. The surgical option may be a partial meniscectomy, the objective being to alleviate the patient's symptoms with resection of only that portion of the meniscus that is no longer functioning but is the cause of symptoms. Previous studies have questioned the need to perform such surgery and have recommended nonoperative treatment instead. Our goal was to compare the outcome of partial meniscectomy with that of physiotherapy alone for irreparable meniscal tears. HYPOTHESIS: Clinical outcome following arthroscopic partial meniscectomy may differ from that following physiotherapy alone, for patients with symptomatic irreparable meniscal tears. STUDY DESIGN: Nonrandomized prospective cohort study. LEVEL OF EVIDENCE: Level 2. METHODS: Patients satisfying the inclusion criteria chose to undergo knee arthroscopy (group A) or physiotherapy (group B). The diagnosis of a meniscal tear was made on physical assessment and magnetic resonance imaging examination. The meniscal tear was preventing them from continuing with their regular weightbearing exercise. Outcomes of interest were the following patient-reported outcomes (PROs): the Knee Osteoarthritis Outcome Score (KOOS) and Tegner Activity Score (TAS), with minimal clinically important differences being 10 and 1, respectively. PROs were completed at baseline, and at 1-year and 2-year follow-up. Changes in scores within and between groups were compared using analysis of variance and Wilcoxon tests (P <0.05). A power analysis demanded 65 patients in each group to produce a power of 80% and a P value of 5%. RESULTS: Of 528 patients enrolled in the study, 10 were lost to follow-up and 8 were excluded. Data were complete for 269 in group A, and 228 in Group B. Group A and B were similar in terms of age (41.1 years, SD 7.8 vs 40 years, SD 13.3), body mass index (22.5 kg/m2, SD 3.1 vs 23.1 kg/m2, SD 2.3), radiographic grade of osteoarthritis (median grade 2, range 0-3 in both groups), gender (male:female = 134:135 vs 112:116), and duration of symptoms (44.4 days, SD 5.6 vs 46.6 days, SD 8.8), with P >0.05. At both 1-year and 2-year follow-up, Group A had higher scores in the mean total KOOS (88.8, SD 8.0 vs 72.4, SD 3.8), as well as in all subscales within the KOOS, and the TAS (median 7, range 5-9 vs median 5, range 3-6), with P <0.001 for each variable. CONCLUSION: Performing a knee arthroscopy with partial meniscectomy is associated with improved KOOS and TAS, relative to treatment with physiotherapy alone, at 2-year follow-up. CLINICAL RELEVANCE: Physically active patients with symptomatic irreparable meniscal tears may experience a better clinical outcome following knee arthroscopy, relative to to physiotherapy alone.

Histologic Remission (NANCY Index) is Superior to Endoscopic Mucosal Healing in Predicting Relapse Free Survival in Patients With Ulcerative Colitis in Clinical and Endoscopic Remission.

BACKGROUND: Histologic activity is recognized as an important predictor of relapse in ulcerative colitis (UC) patients. Current treatment targets aim at mucosal healing; however, many patients continue to have histologic activity. GOALS: The aim was to assess histologic activity using the validated Nancy histologic index (NHI) score as a predictor of future relapse amongst UC patients in endoscopic and clinical remission. STUDY: In this retrospective cohort study, UC patients in clinical and endoscopic remission at a single tertiary center between 2015 and 2018, who underwent a surveillance colonoscopy were included. Clinical remission was defined by partial Mayo score (MSp) <2, and endoscopic remission was defined by Mayo endoscopic subscore (MES) ≤1. Histologic remission was defined by NHI <2. Predictive factors associated with the primary endpoint of clinical relapse were analyzed. RESULTS: A total of 74 of 184 UC patients were included in the study. Amongst this cohort, 33 patients (45%) demonstrated histologic activity (NHI >1) at enrollment. The median follow-up time was 42 months (interquartile range: 26 to 63 mo) with median relapse free period of 30 months (interquartile range: 18 to 48 mo). Kaplan-Meier analysis demonstrated patients with MES 0 ( P =0.02) and histologic remission ( P <0.0001) had significantly longer relapse free survival. On multivariate analysis only histologic activity remained an independent risk factor of future clinical relapse (hazard ratio: 4.36, confidence interval: 1.68-11.27, P =0.002). CONCLUSION: Histologic remission using the NHI independently predicts significantly longer relapse free survival and may be a superior therapeutic target than endoscopic remission.

Diffuse large B-cell lymphoma and red cell autoimmunity: clinical role and pathogenesis.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of B-cell non-Hodgkin lymphoma (B-NHL) with significant morbidity and mortality despite advancements in treatment. Lymphoma and autoimmune disease both result from breakdowns in normal cell regulatory pathways, and epidemiological studies have confirmed both that B-NHL is more likely to develop in the setting of autoimmune diseases and vice versa. Red cell immunity, as evidenced by direct antiglobulin test (DAT) positivity, has been linked to DLBCL and more recently the pathogenic causes of this association have begun to be better understood using molecular techniques. This project aimed to explore the relationship between red cell autoimmunity and DLBCL. DAT positivity was more common in DLBCL as compared to healthy controls (20.4% vs 3.7%, p=0.0005). Univariate analysis found a non-significant trend towards poorer overall survival in the DAT positive (DAT+) compared to the DAT negative (DAT-) groups (p=0.087). High throughput sequencing was used to compare mutations in DLBCL from DAT+ and DAT- patients. The most frequently mutated genes in 15 patient samples were KMT2D (n=13), MYOM2 (n=9), EP300 (n=8), SPEN (n=7), and ADAMTSL3 (n=7), which were mutated in both DAT+ and DAT- groups. BIRC3 (n=3), FOXO1 (n=3) and CARD11 (n=2) were found to be mutated only in samples from the DAT+ group. These gene mutations may be involved in disease development and progression, and potentially represent targets for future therapy. The immunoglobulin genotype IGHV4-34 is seen more frequently in DLBCL clones than in normal B cells and has intrinsic autoreactivity to self-antigens on red cells, which is largely mediated by two motifs within the first framework region (FR1); Q6W7 and A24V25Y.26 These motifs form a hydrophobic patch which determines red cell antigen binding and are frequently mutated away from self-reactivity in normal B cells. If this does not occur this may provide constant B cell receptor signalling which encourages lymphoma development, a theory known as antigen driven lymphomagenesis. As with previous studies, IGHV4-34 was over-represented (15.6%) in our DLBCL cohort. Furthermore, of 6 IGHV4-34-expressing DLBCL samples five had unmutated hydrophobic patch mutations providing further evidence for antigen-driven lymphomagenesis. Mutation analysis of these five samples demonstrated high frequency of mutations in several genes, including CREBBP and NCOR2. Further research could explore if mutations in CREBBP and NCOR2 work in conjunction with the preserved QW and AVY motifs to promote lymphomagenesis in IGHV4-34-expressing B cells, and if so, could guide future targeted therapy.

Modified iliotibial band tenodesis versus lateral extracapsular tenodesis, to augment anterior cruciate ligament reconstruction: a 2-year randomized controlled trial.

BACKGROUND: Residual instability following anterior cruciate ligament (ACL) reconstruction is associated with disruption of the anterolateral complex (ALC). Our goal was to conduct a randomized controlled trial comparing the effectiveness of modified Iliotibial tenodesis (MITBT) versus lateral extracapsular tenodesis (LET) to correct this residual instability. METHODS: Group 1 underwent MITBT, Group 2 LET, added to the ACL reconstruction. Outcomes of interest were Tegner activity Scores (TAS), international knee documentation committee score (IKDC), knee osteoarthritis outcome score (KOOS), ACL related quality of life (ACL QoL), recurrent ACL rupture and meniscal tears. Follow-up was 2 years. Statistical analysis used chi-squared tests, frequency statistics and generalized linear models. We have followed the guidelines outlined in the CONSORT statement. RESULTS: A total of 164 patients were randomized, 84 to Group 1, 80 to Group 2. Group 1 had higher TAS than Group 2, at 2 years (median 8, range 7-10 vs. median 7, range 5-9, P<0.001). Group 1 had higher ACL QoL scores at 1 and 2 years post-surgery (82.1, SD2.7 vs. 67.9, SD 4.0, P< 0.001 and 82.5, SD 2.6 vs. 68.8, SD 3.8, P<0.001, respectively), and higher KOOS Sport/recreation subscale at both 1 and 2 years (91.5, SD4.3 vs. 78.3, SD7.9, P<0.001 and 91.8, SD4.8 vs. 80.4, SD 9.5, P<0.001). Risk of recurrent ACL rupture (0% vs. 5%, P = 0.040-0.05) and medial meniscal tear (2.4% vs. 14%, P = 0.007-0.02) were lower in Group 1. CONCLUSION: Augmentation of ACL reconstruction with the MITBT, rather than the LET, was associated with improved outcomes, and lower risks of recurrent ACL rupture and medial meniscal tears.

BMI is important in predicting the loss of response in inflammatory bowel disease patients on tumour necrosis factor-α inhibitors.

INTRODUCTION: Obesity is an emerging phenomenon among patients with inflammatory bowel disease (IBD). This study aims to evaluate whether the response to tumour necrosis factor-α (TNF-α) inhibitors (infliximab and adalimumab) could be influenced by BMI in IBD. METHODS: We identified a cohort of 181 IBD patients attending a single-tertiary centre, naive to biologic therapy and stratified them according to their BMI. The primary outcome is the first occurrence of loss of response (LOR). RESULTS: The median BMI was 26 kg/m2 (15-63 kg/m2). Approximately 68% of patients had LOR on both adalimumab (ADA) (n = 52) and infliximab (IFX) (n = 71). However, 83% on ADA with BMI ≥30 kg/m2 had LOR compared to 61% on IFX with BMI ≥30 kg/m2. For patients on ADA, Cox regression analysis revealed that after accounting for age, sex, disease type, duration of disease, fistulising disease, smoking status, haemoglobin, C-reactive protein, albumin and platelet levels, there were statistically significant associations between BMI (≥30 kg/m2 vs. <30 kg/m2) and LOR [P = 0.010; hazard ratio (HR) 3.2; confidence interval (CI), 1.3-7.6]. However, for patients on IFX, after accounting for the same factors, the only significant factor was the association of lower rate of LOR with higher albumin levels (P = 0.024; HR 0.95; CI, 0.91-0.99). There was an increased accelerated time to LOR for patients on ADA with BMI ≥30 kg/m2 compared to BMI <30 kg/m2 (P = 0.026). However, there was no difference in time to LOR for patients on IFX (P = 0.177). CONCLUSION: BMI is important in predicting the LOR among IBD patients on TNF-α inhibitors, especially among patients receiving ADA.

The association of age with continuous positive airway pressure ventilation acceptance in an outpatient cohort of patients with obstructive sleep apnea.

STUDY OBJECTIVES: This study examined the association between age and continuous positive airway pressure (CPAP) acceptance in a consecutive series of patients with obstructive sleep apnea being managed in a physician-led outpatient CPAP acclimatization program in Canberra, Australia. METHODS: We performed a retrospective consecutive case series analysis of registry data collected from patients attending the Canberra Hospital PAP Acclimatization Clinic between 2011 and 2019. Data on patient demographics, diagnostic polysomnography results, CPAP device download parameters during acclimatization, and overall CPAP acceptance at the end of acclimatization were extracted from the Clinic Registry. Analysis of variance and chi-square were used to assess for associations between patient age, CPAP acceptance, and other clinical characteristics. Univariate and stepwise multiple logistic regression was used to identify predictors of CPAP acceptance. RESULTS: We found that 1,075 consecutive CPAP trials among 1,043 patients were eligible for inclusion. CPAP acceptance was lower in those aged > 75 years compared with those aged ≤ 75 years (odds ratio: 0.57; 95% confidence interval, 0.36-0.92; P = .02). Patients aged > 75 years had lower body mass index, had higher initial and final visit 95th percentile mask leak, and were less likely to be CPAP naïve. Using univariate regression, younger age, severe obstructive sleep apnea, obesity, shorter trial duration, more clinic visits, higher initial visit CPAP usage, and lower final visit mask leak were predictors of CPAP acceptance. In a multiple logistic regression model, younger age, severe obstructive sleep apnea, shorter trial duration, more clinic visits, higher first visit usage, and lower final visit leak predicted acceptance. CONCLUSIONS: Older age is associated with lower CPAP acceptance. The factors contributing to this association are unclear and require further investigation. CITATION: Han M, Wee R, Shadbolt B, Huang H-CC. The association of age with continuous positive airway pressure ventilation acceptance in an outpatient cohort of patients with obstructive sleep apnea. J Clin Sleep Med. 2022;18(1):217-224.

Accuracy of standard magnetic resonance imaging sequences for meniscal and chondral lesions versus knee arthroscopy. A prospective case-controlled study of 719 cases.

BACKGROUND: Magnetic resonance imaging (MRI) is commonly used for diagnosis and as a research tool, but its accuracy is questionable. The goal of this study was to compare the accuracy of knee MRI with clinical assessment for diagnosing meniscal tears, and to determine the accuracy of MRI for grading chondral lesions, relative to arthroscopy. METHODS: Physically active patients presenting with mechanical symptoms warranting a knee arthroscopy and satisfying the inclusion criteria, had both a knee arthroscopy and MRI performed. Arthroscopic findings were compared with those of MRI, using the International Chondral Research Society grading for chondral damage, and the presence or absence of a meniscal tear. RESULTS: A total of 719 patients were recruited over a period of 6.5 years, average age 52 years (standard deviation, SD 5.2), male:female = 493:226. Kappa scores with standard errors (SE) for agreement between MRI and knee arthroscopy were 0.41 (SE 0.1) for medial meniscal tears, and 0.44 (SE 0.1) for lateral meniscal tears. For the grade of chondral damage, the Kappa scores with SE values were 0.09 (0.1), 0.17 (0.1), and 0.22 (0.07) for anterior, medial and lateral compartments, respectively. Using areas under the receiver operating characteristic curves, we found clinical assessment was more accurate than MRI for diagnosis of lateral meniscal tears (P < 0.001), and of similar accuracy for the diagnosis of medial meniscal tears (P = 0.12). CONCLUSIONS: MRI has relatively poor correlation with arthroscopic findings for grading the chondral damage and was less accurate than clinical assessment for the diagnosis of lateral meniscal tears.

The American Joint Committee on Cancer staging for metastatic head and neck cutaneous squamous cell carcinoma: A multi-institutional study of within-stage heterogeneity and impact on prognostic performance.

BACKGROUND: The American Joint Committee on Cancer (AJCC) staging for head and neck cutaneous squamous cell carcinoma (HNcSCC) stratifies risk poorly. We hypothesized that this results from prognostic heterogeneity within N and TNM groups. METHODS: Retrospective analysis of disease-specific survival (DSS) in a multicenter study of 1146 patients with nodal metastases from HNcSCC. RESULTS: The majority of patients were classified as pN2a or pN3b (83.1%) and TNM stage IV (90.6%). On multivariate analysis, there was statistically significant prognostic heterogeneity within these groups based on the number and size of nodal metastases, immunosuppression, and perineural invasion. When stage IV patients were categorized into low, moderate, and high-risk groups based on adverse features, there was wide variation in prognosis with 5-year DSS ranging from 90% to 60% (P < .001). CONCLUSIONS: The AJCC staging system stratifies risk poorly in HNcSCC due to significant prognostic heterogeneity within pN2a, pN3b, and stage IV groups.

Modified Iliotibial Band Tenodesis Is Indicated to Correct Intraoperative Residual Pivot Shift After Anterior Cruciate Ligament Reconstruction Using an Autologous Hamstring Tendon Graft: A Prospective Randomized Controlled Trial.

BACKGROUND: The indications for the addition of anterolateral soft tissue augmentation to anterior cruciate ligament (ACL) reconstruction and its effectiveness remain uncertain. PURPOSE: To determine if modified iliotibial band tenodesis (MITBT) can improve clinical outcomes and reduce the recurrence of ACL ruptures when added to ACL reconstruction in patients with a residual pivot shift. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: Patients with a primary ACL rupture satisfying the following inclusion criteria were enrolled: first ACL rupture, involved in pivoting sports, skeletally mature, no meniscal repair performed, and residual pivot shift relative to the contralateral uninjured knee immediately after ACL reconstruction. Patients were randomized to group A (no further surgery) or group B (MITBT added) and were followed up for 2 years. The patient-reported outcome (PRO) measures used were the International Knee Documentation Committee (IKDC) score, Knee injury and Osteoarthritis Outcome Score (KOOS) subscale of sport/recreation (Sport/Rec), KOOS subscale of quality of life (QoL), Lysholm knee score (LKS), Tegner activity scale (TAS), recurrent ACL ruptures, or need for further surgery in either knee. Analysis of variance was used to compare PROs; the Wilcoxon test was used for the TAS; and the chi-square test was used for recurrence of ACL ruptures, meniscal injuries, and contralateral ACL ruptures (P < .05). RESULTS: A total of 55 patients were randomized: 27 to group A (female:male ratio = 15:12; mean age, 22.3 ± 3.7 years) and 28 to group B (female:male ratio = 17:11; mean age, 21.8 ± 4.1 years). At 2-year follow-up, group A had a similar IKDC score (90.9 ± 10.7 vs 94.2 ± 11.2; respectively; P = .21), lower KOOS Sport/Rec score (91.5 ± 6.4 vs 95.3 ± 4.4, respectively; P = .02), similar KOOS QoL score (92.0 ± 4.8 vs 95.1 ± 4.3, respectively; P = .14), lower LKS score (92.5 ± 4.8 vs 96.8 ± 8.0, respectively; P = .004), lower TAS score (median, 7 [range, 7-9] vs 8 [range, 8-10], respectively; P = .03), higher rate of recurrence (14.8% vs 0.0%, respectively; P < .001), similar rate of meniscal tears (14.8% vs 3.6%, respectively; P = .14), and similar rate of contralateral ACL ruptures (3.7% vs 3.6%, respectively; P = .99) relative to group B. CONCLUSION: The augmentation of ACL reconstruction with MITBT reduced the risk of recurrent ACL ruptures in knees with a residual pivot shift after ACL reconstruction and improved KOOS Sport/Rec, LKS, and TAS scores. REGISTRATION: ACTRN12618001043224 (Australian New Zealand Clinical Trials Registry).

PD-L1 expression in papillary thyroid cancer with and without lymphocytic thyroiditis: a cross sectional study.

The impact of concurrent autoimmune thyroid disease on the tumour microenvironment and disease progression in papillary thyroid cancer (PTC) is not well understood. Studies evaluating the programmed cell death ligand 1 (PD-L1) tumour expression in PTC have shown variable results, and the effect of lymphocytic thyroiditis (LT) on tumour PD-L1 expression has not been adequately assessed. The main aim of this study was to determine expression of PD-L1 in PTC with and without LT. We examined 81 PTC cases; 28.5% of all reviewed PTC had presence of LT. In PTC specimens without LT, tumour PD-L1 expression was significantly lower compared to PD-L1 expression in PTC with LT, 6.9% vs 39.1%, respectively. Expression of PD-L1 did not differ with PTC stage, even when sub-categorised according to the presence and absence of LT. Utility of PD- L1 expression as a prognostic marker in thyroid cancer needs to be interpreted with caution.

A pilot randomised clinical trial of 670 nm red light for reducing retinopathy of prematurity.

BACKGROUND: Photobiomodulation by 670 nm red light in animal models reduced severity of ROP and improved survival. This pilot randomised controlled trial aimed to provide data on 670 nm red light exposure for prevention of ROP and survival for a larger randomised trial. METHODS: Neonates <30 weeks gestation or <1150 g at birth were randomised to receive 670 nm for 15 min (9 J/cm2) daily until 34 weeks corrected age. DATA COLLECTED: placental pathology, growth, days of respiratory support and oxygen, bronchopulmonary dysplasia, patent ductus arteriosus, necrotising enterocolitis, sepsis, worst stage of ROP, need for laser treatment, and survival. RESULTS: Eighty-six neonates enrolled-45 no red light; 41 red light. There was no difference in severity of ROP (<27 weeks-p = 0.463; ≥27 weeks-p = 0.558) or requirement for laser treatment (<27 weeks-p = 1.00; ≥27 weeks-no laser treatment in either group). Survival in 670 nm red light treatment group was 100% (41/41) vs 89% (40/45) in untreated infants (p = 0.057). CONCLUSION: Randomisation to receive 670 nm red light within 24-48 h after birth is feasible. Although no improvement in ROP or survivability was observed, further testing into the dosage and delivery for this potential therapy are required.

ANALYSIS OF TIME TO FAILURE AFTER RETINAL DETACHMENT SURGERY.

PURPOSE: To present the distribution of time to retinal redetachment in eyes undergoing retinal detachment surgery, using a method for adjusting time to outcome in eyes with silicone oil or heavy liquid tamponade ("oil-filled eyes"). METHODS: Data from two Australian centers were used. Adjusted time to outcome was measured from the date of tamponade removal in oil-filled eyes, unless failure was diagnosed with tamponade in situ. RESULTS: 188/1257 failures were identified (15.0%). Using unadjusted time to outcome, failures in oil-filled eyes occurred later than non-oil-filled eyes (median time to failure 57 vs. 28 days, P < 0.001). After adjustment, the distribution of time to failure was similar for oil-filled and non-oil-filled eyes (median 25 vs. 28 days, P = 0.68). Larger detachments, eyes with ≥Grade B proliferative vitreoretinopathy and eyes receiving surgery for recurrent detachments were more likely to fail, but the time to failure was similar regardless of risk. CONCLUSION: Adjustment of time to outcome resulted in a similar distribution of time to failure in oil-filled and non-oil filled eyes and was similar in low- and high-risk eyes. The use of adjusted time to outcome will support consistent collection and interpretation of outcomes across different jurisdictions where time to oil removal may vary.

Temporal impact of the publication of guidelines and randomised evidence on the adoption of hypofractionated whole breast radiotherapy for early-stage breast cancer.

INTRODUCTION: Clinical data supporting the use of hypofractionated whole breast radiotherapy (HF-WBRT) in early-stage breast cancer patients have accumulated over the last decade. Despite the availability of the published evidence, the adoption rate of HF-WBRT has been slower-than-expected. We sought to assess the temporal impact of the publication of the guidelines and randomised evidence on the practice pattern of HF-WBRT and identify clinical predictors of its utilisation. METHODS: Women with early-stage breast cancer who received adjuvant WBRT at Canberra Health Services between 2008 and 2016 were identified from clinical databases. The patterns of HF-WBRT use were analysed in relation to pre-specified time periods (before and after the guideline publications) in the entire cohort as well as in a patient subset fulfilling the criteria for HF-WBRT according to the guidelines (referred to as 'guideline-endorsed subset'). The impact of clinical variables, treating clinicians and the time periods on the adoption of HF-WBRT was assessed by hierarchical multivariate logistic regressions. RESULTS: Of the entire cohort (n = 1171), the guideline-endorsed subset constituted 51.6% (n = 604) of the patients. HF-WBRT was utilised in 32.8% of the entire cohort and 46.2% of the guideline-endorsed subset. Between 2008 and 2016, HF-WBRT use rate increased from 12.1% to 56.6% in a non-linear pattern. Release of international and local consensus guidelines significantly correlated with the increase in HF-WBRT utilisation rate. The use of chemotherapy and/or tumour bed boost radiotherapy (TBBR), chest wall sepJMIROtion distance (CWSD) and patient age were significant predictors of HF-WBRT use on multivariate analyses. After factoring in the effects of individual clinicians and the time periods on hierarchical multivariate analyses, the use of chemotherapy, TBBR, and CWSD remained as significant variables. Clinicians contributed to the variability in the HF-WBRT adoption pattern. CONCLUSION: The temporal uptake pattern and the predictors of adjuvant HF-WBRT use in early breast cancer patients largely reflected the accumulating clinical evidence and the publication of the consensus guidelines. This study identified potentially modifiable factors associated with slower-than-expected uptake rate of HF-WBRT. Understanding why there is variability in clinicians' readiness to adopt the abbreviated treatment despite the availability of advanced radiotherapy techniques and the updated evidence is an important step towards formulating effective strategies to optimise the radiotherapeutic management of this common malignancy.

Recurrence in early breast cancer: Analysis of data from 3,765 Australian women treated between 1997 and 2015.

BACKGROUND: Evidence suggests recent improvements in outcome in early breast cancer (EBC). AIM: To analyse recurrence in women with EBC from our region from 1997 to 2015. METHODS: We analysed recurrence in 3,765 women with EBC. Median follow up was 83·0 months. 62·5% had a symptomatic presentation. 81·8% were hormone receptor positive and 38·5% were node positive. Lymphovascular invasion (LVI) was present in 24·3%. Of the 2,686 women entered from 2002 onwards tested for HER2 status, 72·7% had a luminal tumour, 15·2% had a HER2+ tumour and 12·1% had a triple negative (TN) tumour. RESULTS: Recurrence occurred in 459 (12·2%), predominantly in distant sites (71·7%). In women entered from 2002 onwards, the five and 10 year recurrence rates were significantly lower in the luminal group than the HER2+ and the TN groups. Few recurrences occurred in HER2+ and TN cancers after 36 months. On multivariate analysis the following were associated with a significantly increased risk of recurrence: nodal involvement (p < 0·0001), tumour grade (p < 0·0001), symptomatic presentation (p < 0·0001), presence of LVI (p = 0·001), non-luminal tumour type (p < 0·0001) and tumour size >50 mm (p = 0·02). CONCLUSION: The recurrence rate in this series was much lower than in previous older series. Lymph node involvement, tumour grade, symptomatic presentation, presence of LVI, non-luminal tumour type and tumour size (>50 mm) were associated with an increased risk of recurrence. We strongly recommend that clinicians include the presence of LVI and symptomatic presentation as well as the other established tumour factors, when assessing the risk of recurrence in women with EBC.

Ankle Lateral Ligament Augmentation Versus the Modified Broström-Gould Procedure: A 5-Year Randomized Controlled Trial.

BACKGROUND: "Ankle sprain" is a common injury, and >20% of patients may develop chronic instability for which surgery is indicated. The modified Broström-Gould (MBG) procedure remains the gold standard; however, there are a number of relative contraindications to this procedure, and the longer-term outcomes after the MBG have been questioned. An alternative procedure is augmentation of a primary repair with a ligament augmentation reconstruction system (LARS). PURPOSE: To conduct a randomized controlled trial testing the null-hypothesis that there is no difference in patient scored outcomes and activity levels, between patients undergoing a MBG procedure compared with those undergoing a primary repair with LARS augmentation, for lateral ligament instability of the ankle. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Patients who satisfied the inclusion criteria were invited to take part in the study. Patients were randomly allocated to undergo the LARS or MBG procedure. Both groups followed similar postoperative rehabilitation. Patients completed the Foot and Ankle Outcome Score (FAOS) before surgery and then at 1, 2, and 5 years after surgery. Tegner activity scores were recorded at 5years. The scores in the 2 groups were compared via statistical analysis ( P < .05). RESULTS: Of the 50 patients satisfying the inclusion criteria, 47 agreed to take part in the study. Twenty-two were randomized to the LARS group and 25 to the MBG group. At 5 years, follow-up data were complete for 20 patients in the LARS group and 21 in the MBG. There were 2 failures in the MBG group and 0 in the LARS group. The LARS group had significantly better improvement in total FAOS at 1 year (mean ± SD, 92.4 ± 2.5 vs 78.2 ± 3.4, P = .005), 2 years (94.0 ± 3.0 vs 78.0 ± 5.2, P = .003), and 5 years (93.7 ± 6.0 vs 75.1 ± 5.5, P = .002) after surgery. The 5-year Tegner activity scores were higher in the LARS group (8.25 ± 1.1 vs 7.2 ± 0.9, P = .03). CONCLUSION: Among physically active patients with chronic lateral ligament instability, primary repair combined with LARS results in better total FAOS at 5-year follow-up and higher Tegner activity scores as compared with the MBG procedure. REGISTRATION: ACTRN12618000906257 (Australia New Zealand Clinical Trial Registry).

The Augmentation of Revision Anterior Cruciate Ligament Reconstruction With Modified Iliotibial Band Tenodesis to Correct the Pivot Shift: A Computer Navigation Study.

BACKGROUND: Iliotibial band (ITB) tenodesis improves stability and functional outcomes when added to anterior cruciate ligament (ACL) reconstruction. Its precise indications are unknown. Persistence of the pivot shift after revision ACL reconstruction may be one indication. HYPOTHESIS: The addition of ITB tenodesis for a persistent pivot shift after revision ACL reconstruction will improve stability and activity levels. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Adults with recurrent ACL ruptures underwent revision ACL reconstruction, followed by a pivot-shift test before the surgery ended. If the pivot shift was grade 0 or 1, no further surgery was performed (group 1). If it was grade 2 or 3, ITB tenodesis was performed (group 2). The pivot-shift test was performed, graded, and measured using computer navigation before revision ACL reconstruction and after revision ACL reconstruction with and without ITB tenodesis. Tegner activity scores were obtained 2 years after surgery. Groups were compared with regard to anterior translation and internal rotation during the pivot shift as well as Tegner activity scores ( P < .05). RESULTS: There were 20 patients in group 1 and 18 in group 2. The mean anterior translation improved in group 1, from 17.7 ± 3.5 mm to 6.6 ± 1.9 mm, and group 2, from 18.5 ± 3.3 mm to 6.1 ± 1.2 mm, after revision ACL reconstruction ( P < .001), with no difference between the groups ( P = .15). After ITB tenodesis, the reduction in anterior translation in group 2 (5.3 ± 1.5 mm) became greater than that in group 1 (6.6 ± 1.9 mm) ( P = .03). In both groups after revision ACL reconstruction, there was a reduction in internal rotation (group 1: 24.2° ± 4.0° to 10.3° ± 1.1°; group 2: 25.4° ± 3.7° to 14.6° ± 2.8°; P < .001), but this change was less in group 2 ( P = .02). After ITB tenodesis, internal rotation in group 2 (8.3° ± 2.6°) became less than that in group 1 (10.3° ± 1.1°) ( P = .02). The mean Tegner activity scores in group 1 were 8.1 ± 1.1 before surgery and 7.4 ± 0.9 after surgery, while in group 2 they were 7.0 ± 1.3 and 7.2 ± 0.4, respectively, and not significantly different ( P = .29). CONCLUSION: ITB tenodesis improved laxity, although it did not affect activity levels, when there was a persistent pivot shift after revision ACL reconstruction. CLINICAL RELEVANCE: An indication to perform ITB tenodesis is the persistence of a grade ≥2 pivot shift after revision ACL reconstruction.

Smoking in the family is most predictive of the development of childhood asthma in preterm babies <30 weeks gestation: Results of the Respiratory Outcomes Study 2 (RESPOS2).

OBJECTIVES: The Respiratory Outcomes Study 2 (RESPOS2) investigated the relationship between neonatal outcomes (specifically, chronic lung disease [CLD]) and environmental factors on the development of asthma and atopic outcomes at primary school age for preterm babies (PBs) <30 weeks gestational age (GA). METHODS: The study included all surviving PBs <30 weeks GA admitted to the Neonatal Intensive Care Unit at Canberra Hospital, Australian Capital Territory between 2007 and 2009. Parents were sent a questionnaire regarding asthma and atopy symptoms when the PBs were aged 5-7 years old. Data were compared based on CLD status. RESULTS: There were 103 PBs included in the study with a 68.9% response rate to the respiratory questionnaire (71/103). Of these PBs, 15/71 (21.1%) received a diagnosis of CLD. There were no significant differences with regards to asthma, hay fever or eczema in PBs either with or without CLD. The most significant predictor for the development of asthma was smoking in the family (Odds Ratio [OR]: 11.66, 95% Confidence Interval [CI]: 2.01-67.56) with a trend toward significance for family history of asthma (OR: 3.83, 95% CI: 0.85-17.25). CONCLUSION: The RESPOS2 has confirmed previous reports that CLD in PBs <30 weeks GA is not associated with the development of childhood asthma, hay fever or eczema. In our group of PBs, the strongest predictor of the development of asthma was smoking in the family.

Increased use of heated humidified high flow nasal cannula is associated with longer oxygen requirements.

AIM: There has been an increased use of heated humidified high flow nasal canula (HFNC) in premature babies (PBs) admitted to our neonatal unit. The aim of this study is to identify clinical characteristics in PBs < 29 weeks gestational age (GA) that distinguish between those who did not or did receive HFNC. METHODS: This study compared prospectively collected data from 2010 to 2012. Comparisons were undertaken between PBs<29 weeks GA who received continuous positive airway pressure (CPAP: 44/72 (61.1%)) to those who received both CPAP and HFNC (28/72 (38.9%)). Data were analysed using general linear models. RESULTS: There were no significant differences in baseline characteristics between the groups (GA: 27.6 ± 1.1 vs. 27.5 ± 1.1 (weeks), birth weight: 1066 ± 209 vs. 1057 ± 304 (grams) respectively). When analysing outcome measures with multivariate analysis, we found the corrected GA to cease CPAP and oxygen were significantly longer in the HFNC group (31.2 ± 2.1 vs. 32.7 ± 2.0 weeks, P = 0.01 and 32.8 ± 3.5 vs. 36.5 ± 2.8 weeks, P < 0.0001 respectively). CONCLUSIONS: Increased use of HFNC has been associated with increased oxygen requirements. These findings highlight the need to review the use of HFNC in small PBs.

Impact of Mild-to-Moderate Chronic Kidney Disease on One Year Outcomes after Percutaneous Coronary Intervention.

BACKGROUND/AIM: Patients with severe chronic kidney disease (CKD) have a higher risk of adverse events after percutaneous coronary intervention (PCI). There is conflicting evidence regarding the benefit of drug-eluting stents (DES) in patients with CKD. This study is aimed at assessing the effect of mild-to-moderate CKD on PCI outcomes, and determining if DES reduce adverse events amongst these patients. METHOD: We used our PCI database to determine demographic, procedural and outcome variables for 1960 consecutive patients (October 2009-October 2012). Kidney function was measured by the estimated glomerular filtration rate (eGFR - CKD-Epidemiology Collaboration creatinine based). Multivariate analysis was performed to determine independent variables associated with mortality and major adverse cardiovascular events (MACE). RESULTS: The independent variables, predictive of 12-month mortality in PCI patients, were: age >64 years (hazard ratio [HR] 3.10 [95% CI 1.73-5.55], p < 0.001), 3-vessel disease (HR 1.72 [95% CI 1.10-2.68], p = 0.016) and CKD stage. Compared to stage 1 CKD (eGFR >89), HR of death increased in a progressive pattern below eGFR <75: eGFR 60-74, HR 2.40 (95% CI 1.2-4.78), p = 0.013, eGFR 45-59, HR 3.27 (95% CI 1.55-6.9), p = 0.002, eGFR 30-44, HR 4.10 (95% CI 1.82-9.24), p = 0.001, eGFR <30, HR 7.97 (95% CI 3.65-17.40), p < 0.001. In patients with eGFR <75, multivariate analysis demonstrated that DES use was an independent predictor of lower MACE (HR BMS vs. DES 1.8, p = 0.0044). CONCLUSION: Age, severity of CKD and 3-vessel disease were independent predictors of mortality following PCI. The mortality risk in CKD patients increased progressively with eGFR <75. The use of DES was associated with a lower rate of MACE in CKD patients with eGFR <75.

Symptom-to-Balloon Time is a Strong Predictor of Adverse Events Following Primary Percutaneous Coronary Intervention: Results From the Australian Capital Territory PCI Registry.

BACKGROUND: Notwithstanding improvements in door-to-balloon time, adverse event rates after primary PCI have remained steady. We analysed the effect of symptom-to-balloon (STB) time, a reflection of total ischaemic time, on major adverse cardiovascular events (MACE) and explored predictors of prolonged STB time. METHODS: The study population included 1002 consecutive patients (22.4% women) with a mean age of 62.3±13.2 years, who underwent primary PCI during 2008-2014. Groups were compared for STB ≤ and >240min. Primary endpoint was one-year MACE, a composite of death, reinfarction, stent thrombosis or target vessel revascularisation. RESULTS: Symptom-to-balloon time was available in 893 patients of which 588 (65.8%) had STB ≤240min and 305 (34.2%) had STB >240min. The incidence of one-year MACE increased significantly in a stepwise manner with increasing STB time (p for trend=0.003). Symptom-to-balloon time was an independent predictor of one-year MACE along with age >70 years, final TIMI flow <3, three vessel disease, cardiogenic shock and out-of-hospital cardiac arrest. We also performed a multivariate analysis to determine predictors of delayed treatment. Predictors of STB time >240min were age >70 years, female gender, diabetes, absence of prehospital catheter laboratory activation and presentation to a non-PCI centre. CONCLUSION: Incidence of MACE was strongly correlated with STB time and STB time was an independent predictor of MACE. We have identified specific subgroups with prolonged STB times (age >70, female gender, diabetes, absence of prehospital activation and presentation to a non-PCI centre). This information should inform future studies and strategies to minimise delays in these subgroups for improved outcomes.