Reduced time to surgery improves patient-reported outcome after achilles tendon rupture.

Background: Patient outcome after an acute Achilles tendon rupture (ATR) continues to be suboptimal and heterogeneous. Thus, prognostic factors are called for to optimize evidence-based ATR treatment protocols, however, the influence of delayed time from injury to surgery (TTS) on patient outcome after ATR remains largely unknown. Purpose: To determine whether patient outcomes and adverse events after surgical repair of acute ATR are related to delayed TTS. Study Design: Cohort study; Level of evidence, 3. Methods: Two hundred and twenty-eight ATR patients treated with uniform anesthetic and surgical techniques, within 10 days after injury, were retrospectively assessed. TTS depended on a free slot in the operating theatre and neither surgeon nor patient could affect TTS. Patients were assigned into three groups according to trichotomized TTS; short- (72hours). Patient-reported outcome at one-year was assessed using the validated Achilles tendon Total Rupture Score, with scores>80 on a 0- to 100-point scale indicating an overall good outcome. The incidences of adverse events (peri- and postoperative) and deep venous thrombosis were assessed. Results: Shorter TTS was significantly associated with increased rate of good outcome and reduced risk of adverse events. Seventy-one percent (95% CI, 60%-83%) of the patients with short TTS attained a good outcome compared to 44% (95% CI, 33%-56%) of the patients 3 with long TTS (p=.002), and with the intermediate TTS group in between (63%, 95% CI, 47%-78%). The incidence of adverse events was significantly reduced among patients with short TTS 1.4% (95% CI, 1%-4%) as compared to those with intermediate TTS 11% (95% CI, 2%-21%) (p=.035) and to patients with long TTS 14.8% (95% CI, 7%-23%) (p=.003). The risk of sustaining a deep venous thrombosis was not statistically significant different among the three groups (p=.15). Conclusion: Patients with acute ATR operated on within 48 hours after injury yielded better outcomes and a lower number of adverse events compared to patients operated on after 72 hours. These results conform to evidence-based recommendations from other surgical disciplines and should be used as guidelines for optimizing ATR treatment protocols.Swedish Research Council (project nr. 2012-3510)Accepte

STOP leg clots - Swedish multicentre trial of outpatient prevention of leg clots : study protocol for a randomised controlled trial on the efficacy of intermittent pneumatic compression on venous thromboembolism in lower leg immobilised patients

Introduction Leg immobilisation in a cast or an orthosis after lower limb injuries is associated with a high risk of complications of venous thromboembolism (VTE) and hampered healing. Current pharmacoprophylaxes of VTE are inefficient and associated with adverse events. Intermittent pneumatic compression (IPC) could represent a novel, efficient and safe VTE-prophylactic alternative that may enhance injury healing. The aim of STOP leg clots is to assess the efficacy of adjuvant IPC-therapy on reduction of VTE incidence and improvement of healing in lower leg immobilised outpatients. Methods and analysis STOP leg clots is a multicentre randomised controlled superiority trial. Eligible patients (700 patients/arm) with either an acute ankle fracture or Achilles tendon rupture will be randomised to either addition of IPC during lower-leg immobilisation or to treatment-as-usual. The primary outcome will be the total VTE incidence, that is, symptomatic and asymptomatic deep venous thrombosis (DVT) or symptomatic pulmonary embolism (PE), during the leg immobilisation period, approximately 6-8 weeks. DVT incidence will be assessed by screening whole leg compression duplex ultrasound at removal of leg immobilisation and/or clinically diagnosed within the time of immobilisation. Symptomatic PE will be verified by CT. Secondary outcomes will include patient-reported outcome using validated questionnaires, healing evaluated by measurements of tendon callus production and changes in VTE-prophylactic mechanisms assessed by blood flow and fibrinolysis. Data analyses will be blinded and based on the intention-to-treat. Ethics and dissemination Ethical approval was obtained by the ethical review board in Stockholm, Sweden, Dnr 2016/1573-31. The study will be conducted in accordance with the Helsinki declaration. The results of the study will be disseminated in peer-reviewed international journals.Funding Agencies|Swedish research councilSwedish Research CouncilEuropean Commission [Dnr: 2017-00202]</p

Pooled analysis of prospective European studies assessing the impact of using the 21-gene Recurrence Score assay on clinical decision making in women with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative early-stage breast cancer.

PURPOSE: The 21-gene Recurrence Score assay (Oncotype DX) provides prognostic/predictive information in oestrogen receptor positive (ER+) early breast cancer, but access/reimbursement has been limited in most European countries in the absence of prospective outcome data. Recently, two large prospective studies and a real-life 5-year outcome study have been reported. We performed a pooled analysis of prospective European impact studies to generate robust data on impact of use in different clinical subgroups. METHODS: The analysis included four studies (French, German, Spanish, and British) in ER+ human epidermal growth factor receptor 2-negative breast cancer patients (n = 527). Node-positive patients were excluded. RESULTS: The analysis demonstrated that treatment recommendations changed in 32% of patients post-testing; chemotherapy recommendation rate decreased from 55% to 34%. Change rates in the individual studies ranged from 30% to 37%. The highest change rates were in patients originally recommended chemotherapy and in grade II tumours; there was no subgroup without a treatment recommendation change. Notably, 31% of patients with an intermediate Recurrence Score result had a treatment recommendation change suggesting that testing provides actionable information in this group. With the exception of the German study (where chemotherapy rates remained high [41%] post-testing), between-study variability in treatment recommendations decreased post-testing (chemotherapy: from 36-52% to 26-29%; hormonal therapy: from 48-64% to 71-74%). Physicians' confidence regarding treatment recommendations improved in all the studies after testing. CONCLUSION: Recurrence Score testing led to changes in adjuvant chemotherapy use in approximately a third of patients, to an overall reduced chemotherapy use, and to more homogeneous decision making.J.A. acknowledges FIS PI12/00680 RD12/0036/0051, 2014SGR740 intensification grant ISCIII, and A Ll./nPI12/01421 and RD12/0036/0070

Gene profiling reveals a contact allergy signature in most positive Amerchol L-101 patch-test reactions

Background: Diagnosis of contact allergy (CA) to Amerchol L-101 (AL-101), a marker for lanolin allergy, is problematic. Positive patch-test reactions are frequently doubtful or weakly positive and difficult to associate with clinical relevance. Objective: To gain further insight on the allergic or irritant nature of skin reactions induced by AL-101 patch test. Methods: We re-tested in a dose–response fashion, 10 subjects with AL-101 CA and performed comprehensive transcriptomic analysis (gene arrays, quantitative real-time polymerase chain reaction [qRT-PCR]) of samples of their skin reactions. Results: Eight of the 10 CA subjects reacted positively upon re-test, whereas two did not react. Most of AL-101 positive patch tests expressed an allergy signature with strong activation of gene modules associated with adaptive immunity and downregulation of cornification pathway genes. In addition, the breadth of gene modulation correlated with the magnitude of patch-test reactions and the concentration of AL-101 applied. However, we observed that some of the positive patch-test reactions to AL-101 expressed no/few allergy biomarkers, suggesting the induction of an irritant skin inflammation in these samples. Conclusions: This study confirms that AL-101 is an allergen that can cause both contact allergy and contact irritation. Our results also highlight that molecular profiling might help to strengthen clinical diagnosis

Pooled analysis of prospective European studies assessing the impact of using the 21-gene Recurrence Score assay on clinical decision making in women with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative early-stage breast cancer.

PURPOSE: The 21-gene Recurrence Score assay (Oncotype DX) provides prognostic/predictive information in oestrogen receptor positive (ER+) early breast cancer, but access/reimbursement has been limited in most European countries in the absence of prospective outcome data. Recently, two large prospective studies and a real-life 5-year outcome study have been reported. We performed a pooled analysis of prospective European impact studies to generate robust data on impact of use in different clinical subgroups. METHODS: The analysis included four studies (French, German, Spanish, and British) in ER+ human epidermal growth factor receptor 2-negative breast cancer patients (n = 527). Node-positive patients were excluded. RESULTS: The analysis demonstrated that treatment recommendations changed in 32% of patients post-testing; chemotherapy recommendation rate decreased from 55% to 34%. Change rates in the individual studies ranged from 30% to 37%. The highest change rates were in patients originally recommended chemotherapy and in grade II tumours; there was no subgroup without a treatment recommendation change. Notably, 31% of patients with an intermediate Recurrence Score result had a treatment recommendation change suggesting that testing provides actionable information in this group. With the exception of the German study (where chemotherapy rates remained high [41%] post-testing), between-study variability in treatment recommendations decreased post-testing (chemotherapy: from 36-52% to 26-29%; hormonal therapy: from 48-64% to 71-74%). Physicians' confidence regarding treatment recommendations improved in all the studies after testing. CONCLUSION: Recurrence Score testing led to changes in adjuvant chemotherapy use in approximately a third of patients, to an overall reduced chemotherapy use, and to more homogeneous decision making.J.A. acknowledges FIS PI12/00680 RD12/0036/0051, 2014SGR740 intensification grant ISCIII, and A Ll./nPI12/01421 and RD12/0036/0070