Formylated Peptide Receptor-1-Mediated Gut Inflammation as a Therapeutic Target in Inflammatory Bowel Disease.

Background: Formylated peptide receptor (FPR)-1 is a G-coupled receptor that senses foreign bacterial and host-derived mitochondrial formylated peptides (FPs), leading to innate immune system activation. Aim: We sought to investigate the role of FPR1-mediated inflammation and its potential as a therapeutic target in inflammatory bowel disease (IBD). Methods: We characterized FPR1 gene and protein expression in 8 human IBD (~1000 patients) datasets with analysis on disease subtype, mucosal inflammation, and drug response. We performed in vivo dextran-sulfate sodium (DSS) colitis in C57/BL6 FPR1 knockout mice. In ex vivo studies, we studied the role of mitochondrial FPs and pharmacological blockade of FPR1 using cyclosporin H in human peripheral blood neutrophils. Finally, we assess mitochondrial FPs as a potential mechanistic biomarker in the blood and stools of patients with IBD. Results: Detailed in silico analysis in human intestinal biopsies showed that FPR1 is highly expressed in IBD (n = 207 IBD vs 67 non-IBD controls, P < .001), and highly correlated with gut inflammation in ulcerative colitis (UC) and Crohn's disease (CD) (both P < .001). FPR1 receptor is predominantly expressed in leukocytes, and we showed significantly higher FPR1+ve neutrophils in inflamed gut tissue section in IBD (17 CD and 24 UC; both P < .001). Further analysis in 6 independent IBD (data available under Gene Expression Omnibus accession numbers GSE59071, GSE206285, GSE73661, GSE16879, GSE92415, and GSE235970) showed an association with active gut inflammation and treatment resistance to infliximab, ustekinumab, and vedolizumab. FPR1 gene deletion is protective in murine DSS colitis with lower gut neutrophil inflammation. In the human ex vivo neutrophil system, mitochondrial FP, nicotinamide adenine dinucleotide dehydrogenase subunit-6 (ND6) is a potent activator of neutrophils resulting in higher CD62L shedding, CD63 expression, reactive oxygen species production, and chemotactic capacity; these effects are inhibited by cyclosporin H. We screened for mitochondrial ND6 in IBD (n = 54) using ELISA and detected ND6 in stools with median values of 2.2 gg/mL (interquartile range [IQR] 0.0-4.99; range 0-53.3) but not in blood. Stool ND6 levels, however, were not significantly correlated with paired stool calprotectin, C-reactive protein, and clinical IBD activity. Conclusions: Our data suggest that FPR1-mediated neutrophilic inflammation is a tractable target in IBD; however, further work is required to clarify the clinical utility of mitochondrial FPs as a potential mechanistic marker for future stratification.

Endo-anesthesia: a primer.

Gastrointestinal (GI) endoscopy has witnessed a Cambrian explosion of techniques, indications, and expanding target populations. GI endoscopy encompasses traditional domains that include preventive measures, palliation, as alternative therapies in patients with prohibitive risks of more invasive procedures, and indicated primary treatments. But, it has expanded to include therapeutic and diagnostic interventional endosonography, luminal endoscopic resection, third space endotherapy, endohepatology, and endobariatrics. The lines between surgery and endoscopy are blurred on many occasions within this paradigm. Moreover, patients with high degrees of co-morbidity and complex physiology require more nuanced peri-endoscopic management. The rising demand for endoscopy services has resulted in the development of endoscopy referral centers that offer these invasive procedures as directly booked referrals for regional and rural patients. This further necessitates specialized programs to ensure appropriate evaluation, risk stratification, and optimization for safe sedation and general anesthesia if needed. This landscape is conducive to the organic evolution of endo-anesthesia to meet the needs of these focused and evolving practices. In this primer, we delineate important aspects of endo-anesthesia care and provide relevant clinical and logistical considerations pertaining to the breadth of procedures.

Cerebral microbleeds following thoracic endovascular aortic repair.

BACKGROUND: Stroke and neurological injury are a complication of thoracic endovascular aortic repair (TEVAR). Cerebral microbleeds (CMBs) are common in patients with white matter damage to the brain secondary to chronic vasculopathy. The aim of this study was to examine the occurrence of CMBs after TEVAR, and to evaluate their association with patient and procedural factors. METHODS: Patients who underwent TEVAR between September 2018 and January 2020 in two specialist European aortic centres were analysed. All patients underwent postoperative susceptibility-weighted MRI. The location and number of CMBs were identified, and analysed with regard to procedural aspects, clinical outcome, and Fazekas score as an indicator of pre-existing vascular leucoencephalopathy. RESULTS: Some 91 patients were included in the study. A total of 1531 CMBs were detected in 58 of 91 patients (64 per cent). In the majority of affected patients, CMBs were found bilaterally (79 per cent). Unilateral CMBs in the right or left hemisphere occurred in 16 and 5 per cent of patients respectively (P < 0.001). More CMBs were found in the middle cerebral than in the vertebrobasilar/posterior and anterior cerebral artery territories (mean(s.d.) 3.35(5.56) versus 2.26(4.05) versus 0.97(2.87); P = 0.045). Multivariable analysis showed an increased probability of CMBs after placement of TEVAR stent-grafts with a proximal diameter of at least 40 mm (odds ratio (OR) 6.85, 95 per cent c.i. 1.65 to 41.59; P = 0.007) and in patients with a higher Fazekas score on postoperative T2-weighted MRI (OR 2.62, 1.06 to 7.92; P = 0.037). CONCLUSION: CMBs on postoperative MRI are common after endovascular repair in the aortic arch. Their occurrence appears to be associated with key aspects of the procedure and pre-existing vascular leucoencephalopathy.

Long-Term Results of NRG Oncology/RTOG 0321: A Phase II Trial of Combined High Dose Rate Brachytherapy and External Beam Radiation Therapy for Adenocarcinoma of the Prostate.

PURPOSE: To report the long-term outcome of patients with prostate cancer treated with external beam radiation therapy and high dose rate (HDR) brachytherapy from a prospective multi-institutional trial conducted by NRG Oncology/RTOG. METHODS AND MATERIALS: Patients with clinically localized (T1c-T3b) prostate cancer without prior history of transurethral resection of prostate or hip prosthesis were eligible for this study. All patients were treated with a combination of 45 Gy in 25 fractions from external beam radiation therapy and one HDR implant delivering 19 Gy in 2 fractions. Adverse events (AE) were collected using Common Toxicity Criteria for Adverse Events, version 3. Cumulative incidence was used to estimate time to severe late gastrointestinal (GI)/genitourinary (GU) toxicity, biochemical failure, disease-specific mortality, local failure, and distant failure. Overall survival was estimated using the Kaplan-Meier method. RESULTS: One hundred and twenty-nine patients were enrolled from July 2004 to May 2006. AE data was available for 115 patients. Patients were National Comprehensive Cancer Network (NCCN) intermediate to very high risk. The median age was 68, T1c-T2c 91%, T3a-T3b 9%, PSA ≤10 70%, PSA >10 to ≤20 30%, GS 6 10%, GS 7 72%, and GS 8 to 10 18%. Forty-three percent of patients received hormonal therapy. At a median follow-up time of 10 years, there were 6 (5%) patients with grade 3 GI and GU treatment-related AEs, and no late grade 4 to 5 GI and GU AEs. At 5 and 10 years, the rate of late grade 3 gastrointestinal and genitourinary AEs was 4% and 5%, respectively. Five- and 10-year overall survival rates were 95% and 76%. Biochemical failure rates per Phoenix definition at 5 and 10 years were 14% and 23%. The 10-year rate of disease-specific mortality was 6%. At 5 and 10 years, the rates of distant failure were 4% and 8%, respectively. The rates of local failure at 5 and 10 years were 2% at both time points. CONCLUSIONS: Combined modality treatment using HDR prostate brachytherapy leads to excellent long-term clinical outcomes in this prospective multi-institutional trial.

Association between prophylactic low-molecular-weight heparin use in pregnancy and macrosomia: analysis of the Ottawa and Kingston birth cohort.

Essentials Low-molecular-weight heparin (LMWH) is used to prevent venous thromboembolism (VTE) in pregnancy. We evaluated the association between LMWH and large for gestational age (LGA) infants. We found no significant associations between LMWH use and LGA. LMWH does not appear to increase the risk for the delivery of an LGA infant. SUMMARY: Background Low-molecular-weight heparin (LMWH), an anticoagulant, is the recommended drug for thromboprophylaxis and treatment of venous thromboembolism (VTE) in pregnancy. During pregnancy, LMWH is routinely prescribed to mothers with an increased risk of VTE or with a history of thrombosis. Although clinical reports of larger offspring born to women administered LMWH have been noted, no studies to date have evaluated or associated the use of LMWH and large for gestational age (LGA) infants. Objectives To determine whether there is an association between LMWH usage in mothers and the prevalence of LGA. Patients/Methods We performed an analysis of the Ottawa and Kingston (OaK) Birth Cohort and report characteristics of LMWH and association LGA (> 10%ile). We used coarsened exact matching (CEM) methods to account for bias and confounding. Results A total of 7519 women from the OaK Birth Cohort were included; 59 were administered LMWH during pregnancy (0.78%). Mothers prescribed LMWH had significantly greater BMI (P = 0.0001), age (P = 0.0001) and parity (P = 0.02). Gestational length was shorter among women administered LMWH compared to those without treatment (37.7 ± 2.0 vs. 39.2 ± 2.0, P < 0.0001), an iatrogenic finding. The odds ratio of an LGA delivery among women administered LMWH was 1.02 (95% confidence interval [CI], 0.48-2.16; P = 0.96) in unadjusted analyses and was 1.15 (95% CI, 0.49-2.71) in the matched sample adjusted for maternal age, BMI and gestational age. Conclusions These results, although exploratory, provide indirect evidence of no increased risk of LGA infants among women prescribed LMWH.

Sequence of hormonal therapy and radiotherapy field size in unfavourable, localised prostate cancer (NRG/RTOG 9413): long-term results of a randomised, phase 3 trial.

BACKGROUND: The NRG/RTOG 9413 study showed that whole pelvic radiotherapy (WPRT) plus neoadjuvant hormonal therapy (NHT) improved progression-free survival in patients with intermediate-risk or high-risk localised prostate cancer compared with prostate only radiotherapy (PORT) plus NHT, WPRT plus adjuvant hormonal therapy (AHT), and PORT plus AHT. We provide a long-term update after 10 years of follow-up of the primary endpoint (progression-free survival) and report on the late toxicities of treatment. METHODS: The trial was designed as a 2 × 2 factorial study with hormonal sequencing as one stratification factor and radiation field as the other factor and tested whether NHT improved progression-free survival versus AHT, and NHT plus WPRT versus NHT plus PORT. Eligible patients had histologically confirmed, clinically localised adenocarcinoma of the prostate, an estimated risk of lymph node involvement of more than 15% and a Karnofsky performance status of more than 70, with no age limitations. Patients were randomly assigned (1:1:1:1) by permuted block randomisation to receive either NHT 2 months before and during WPRT followed by a prostate boost to 70 Gy (NHT plus WPRT group), NHT 2 months before and during PORT to 70 Gy (NHT plus PORT group), WPRT followed by 4 months of AHT (WPRT plus AHT group), or PORT followed by 4 months of AHT (PORT plus AHT group). Hormonal therapy was combined androgen suppression, consisting of goserelin acetate 3·6 mg once a month subcutaneously or leuprolide acetate 7·5 mg once a month intramuscularly, and flutamide 250 mg twice a day orally for 4 months. Randomisation was stratified by T stage, Gleason Score, and prostate-specific antigen concentration. NHT was given 2 months before radiotherapy and was continued until radiotherapy completion; AHT was given at the completion of radiotherapy for 4 months. The primary endpoint progression-free survival was analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769548. The trial has been terminated to additional follow-up collection and this is the final analysis for this trial. FINDINGS: Between April 1, 1995, and June 1, 1999, 1322 patients were enrolled from 53 centres and randomly assigned to the four treatment groups. With a median follow-up of 8·8 years (IQR 5·07-13·84) for all patients and 14·8 years (7·18-17·4) for living patients (n=346), progression-free survival across all timepoints continued to differ significantly across the four treatment groups (p=0·002). The 10-year estimates of progression-free survival were 28·4% (95% CI 23·3-33·6) in the NHT plus WPRT group, 23·5% (18·7-28·3) in the NHT plus PORT group, 19·4% (14·9-24·0) in the WPRT plus AHT group, and 30·2% (25·0-35·4) in the PORT plus AHT group. Bladder toxicity was the most common grade 3 or worse late toxicity, affecting 18 (6%) of 316 patients in the NHT plus WPRT group, 17 (5%) of 313 in the NHT plus PORT group, 22 (7%) of 317 in the WPRT plus AHT group, and 14 (4%) of 315 in the PORT plus AHT group. Late grade 3 or worse gastrointestinal adverse events occurred in 22 (7%) of 316 patients in the NHT plus WPRT group, five (2%) of 313 in the NHT plus PORT group, ten (3%) of 317 in the WPRT plus AHT group, and seven (2%) of 315 in the PORT plus AHT group. INTERPRETATION: In this cohort of patients with intermediate-risk and high-risk localised prostate cancer, NHT plus WPRT improved progression-free survival compared with NHT plus PORT and WPRT plus AHT at long-term follow-up albeit increased risk of grade 3 or worse intestinal toxicity. Interactions between radiotherapy and hormonal therapy suggests that WPRT should be avoided without NHT. FUNDING: National Cancer Institute.

A prospective study of Rivaroxaban for central venous catheter associated upper extremity deep vein thrombosis in cancer patients (Catheter 2).

INTRODUCTION: Patients with cancer are at increased risk of thrombosis, particularly those with central venous catheter (CVC) placement, which may predispose to the development of upper extremity deep vein thrombosis (UEDVT). Standard treatment includes low molecular weight heparin (LMWH) or LMWH bridged to warfarin. The direct oral anticoagulants (DOACs) have become standard of care for uncomplicated venous thromboembolism (VTE), but research in patients with cancer is ongoing. OBJECTIVES: To assess rivaroxaban monotherapy in patients with cancer who develop UEDVT due to CVC for preservation of line function, and safety outcomes of VTE recurrence, bleeding risk and death. MATERIALS AND METHODS: Patients ≥18years of age with active malignancy and symptomatic proximal UEDVT with or without pulmonary embolism (PE), associated with a CVC, were eligible. Treatment included rivaroxaban 15mg oral twice daily for 3weeks, followed by 20mg oral daily for 9weeks. Patients were followed clinically for 12weeks to assess for line function, recurrent VTE and bleeding. RESULTS: Seventy patients (47 women) were included, with mean age 54.1years. The most common malignancy was breast cancer (41%). Preservation of line function was 100% at 12weeks. The risk of recurrent VTE at 12weeks was 1.43%, with one episode of fatal PE. 9 patients (12.9%) experienced 11 total bleeding episodes. CONCLUSIONS: Rivaroxaban showed promise in treating CVC-UEDVT in cancer patients, resulting in preserved line function. However, bleeding rates and a fatal pulmonary embolism on treatment are concerning safety outcomes necessitating further study before rivaroxaban can be recommended.

Association between remote major venous thromboembolism risk factors and the risk of recurrence after a first unprovoked episode.

Essentials Is remote exposure to major venous thromboembolism (VTE) risk factor related to lower recurrence? We analyzed data from the REVERSE study, a cohort of patients with no recent major risk factor. We found no association between remote risk factors and the risk of recurrence. Patients with remote VTE risk factor should be managed as having had an unprovoked VTE. SUMMARY: Background It has been shown that the risk of recurrence of venous thromboembolism (VTE) is significantly lower when provoked by a major risk factor such as surgery or trauma compared with an event that was unprovoked. Objectives In this study we aimed to assess the association between remote exposure (3-12 months prior to VTE) to major VTE risk factors and the risk of recurrent VTE. Methods This was a post-hoc analysis of the REVERSE study, a prospective cohort of 646 patients with a first VTE, not provoked by a recent (< 3 months) major risk factor. Results We found no difference in the recurrence rate in patients with or without remote exposure to major VTE risk factors, including immobilization (hazard-ratio [HR], 1.4; 95% confidence interval, 0.7-2.6), surgery (HR, 0.8; 0.3-1.9) and trauma (HR, 1.3; 0.5-3.6). Conclusion None of the tested risk factors were associated with a lower risk of recurrence during follow-up. Patients with remote exposure to major risk factors at the time of a first VTE should not be managed differently from patients with no VTE risk factors.

Advantages of melodic over rhythmic movement sonification in bimanual motor skill learning.

An important question for skill acquisition is whether and how augmented feedback can be designed to improve the learning of complex skills. Auditory information triggered by learners' actions, movement sonification, can enhance learning of a complex bimanual coordination skill, specifically polyrhythmic bimanual shape tracing. However, it is not clear whether the coordination of polyrhythmic sequenced movements is enhanced by auditory-specified timing information alone or whether more complex sound mappings, such as melodic sonification, are necessary. Furthermore, while short-term retention of bimanual coordination performance has been shown with movement sonification training, longer term retention has yet to be demonstrated. In the present experiment, participants learned to trace a diamond shape with one hand while simultaneously tracing a triangle with the other to produce a sequenced 4:3 polyrhythmic timing pattern. Two groups of participants received real-time auditory feedback during training: melodic sonification (individual movements triggered a separate note of a melody) and rhythmic sonification (each movement triggered a percussive sound), while a third control group received no augmented feedback. Task acquisition and performance in immediate retention were superior in the melodic sonification group as compared to the rhythmic sonification and control group. In a 24-h retention phase, a decline in performance in the melodic sonification group was reversed by brief playback of the target pattern melody. These results show that melodic sonification of movement can provide advantages over augmented feedback which only provides timing information by better structuring the sequencing of timed actions, and also allow recovery of complex target patterns of movement after training. These findings have important implications for understanding the role of augmented perceptual information in skill learning, as well as its application to real-world training or rehabilitation scenarios.

Net clinical benefit of hospitalization versus outpatient management of patients with acute pulmonary embolism.

Essentials Clinical benefit of hospitalization vs. outpatient treatment in pulmonary embolism (PE) is unknown. We performed a propensity matched cohort study of hemodynamically stable PE patients. Regardless of the risk assessment, hospitalized patients had the highest rate of adverse event. If confirmed, ambulatory care of normotensive PE patients may be preferred whenever possible. SUMMARY: Background The decision to hospitalize or not patients with acute pulmonary embolism (PE) is controversial. Despite the advantages of close monitoring, hospitalization by itself may lead to in-hospital complications and potentially worsen the prognosis of PE patients. Objectives To determine the net clinical benefit of hospitalization vs. outpatient management of normotensive patients with acute pulmonary embolism (PE). Methods Retrospective cohort propensity score analysis (radius marching with replacement). Hemodynamically stable PE patients treated as outpatients or inpatients were matched to balance out differences for 28 patient characteristics and known risk factors for adverse events. The primary outcome was the rate of adverse events at 14 days, including recurrent venous thromboembolism, major bleeding or death. Results Among 1127 eligible patients, 1081 were included in the matched cohort, 576 treated as inpatients and 505 as outpatients. The 14-day rate of adverse events was 13.0% for inpatients and 3.3% for outpatients (adjusted OR, 5.07; 95% CI, 1.68-15.28). The 3-month rate was 21.7% for inpatients and 6.9% for outpatients (OR, 4.90; 95% CI, 2.62-9.17). In the high-risk subgroup (Pulmonary Embolism Severity Index class III-V; n = 597), the 14-day rate of adverse events was 16.5% for hospitalized patients vs. 4.5% for outpatients (OR, 4.16; 95% CI, 1.2-14.35). Conclusion Outpatient treatment of hemodynamically stable PE patients seems to be associated with a lower rate of adverse events than hospitalization and, if confirmed, may be considered as first-line management in patients not requiring specific in-hospital care, regardless of their initial risk stratification, if proper outpatient care can be provided.

A randomised trial of the cool pad pillow topper versus standard care for sleep disturbance and hot flushes in women on endocrine therapy for breast cancer.

PURPOSE: Quality of life in women receiving adjuvant endocrine therapy for breast cancer (BC) may be impaired by hot flushes and night sweats. The cool pad pillow topper (CPPT) is a commercial product, promoted to improve quality of sleep disrupted by hot flushes. This study aimed to identify if the CPPT reduces severity of sleep disturbance by minimising effects of hot flushes. METHODS: This randomised phase II trial, recruited women with BC, on adjuvant endocrine therapy, experiencing hot flushes and insomnia. Participants were randomised (stratified by baseline sleep efficiency score (SES) and menopausal status) to the intervention arm (CPPT + standard care) or control arm (standard care). Participants completed Hospital Anxiety and Depression Scale and Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaires and fortnightly sleep/hot flush diaries (where responses were averaged over 2-week periods). The primary endpoint was change in average SES from -2 to 0 weeks to 2 to 4 weeks. RESULTS: Seventy-four pre- (68.9 %) and post-menopausal (31.1 %) women were recruited. Median age was 49.5 years. Endocrine therapies included tamoxifen (93.2 %). Median SES at weeks 2 to 4 improved in both arms but the increase on the intervention arm was almost twice that on the control arm (p = 0.024). There were significantly greater reductions in hot flushes and HADS depression in the intervention arm (p = 0.09 and p = 0.036, respectively). There were no significant differences in FACT-B or HADS anxiety. CONCLUSION: This study supports the use of the CPPT as an aid to reduce sleep disturbance and the frequency/severity of hot flushes.

Prothrombin G20210A mutation and lower extremity peripheral arterial disease: a systematic review and meta-analysis.

OBJECTIVE/BACKGROUND: Despite being an important risk factor for venous thromboembolism, the role of the prothrombin G20210A mutation in patients with arterial disease remains unclear. The aim of this review was to evaluate the association of prothrombin G20210A and lower extremity peripheral arterial disease (PAD). METHODS: This was a systematic review and meta-analysis of case-control studies. A systematic review of electronic databases, including MEDLINE and Embase, was conducted to assess the prevalence of prothrombin G20210A in patients with lower extremity PAD. The main outcome was the prevalence of prothrombin G20210A in patients with lower extremity PAD. The random effects model odds ratio (OR) was used as the primary outcome measure. RESULTS: The initial electronic search identified 168 relevant abstracts of which five studies evaluating 1,524 cases of PAD and 1,553 controls were included. Prothrombin G20210A was found in 70 of 1,524 patients with lower extremity PAD and 44 of 1,553 of the controls (random effects OR 1.68, 95% confidence interval [CI] 0.8-3.2). In those with critical limb ischemia (CLI), the prevalence of prothrombin G20210A was 23 of 302 compared with 31 of 1,253 of the controls (OR 3.2, 95% CI 1.6-6.1). CONCLUSION: Despite finding no significant association between lower extremity PAD and prothrombin G20210A, the meta-analysis suggests that the prevalence of prothrombin G20210A is significantly elevated in those with atherosclerotic occlusive disease of the lower extremities presenting with CLI. Well-designed prospective cohort studies evaluating the role of prothrombin G20210A as a predictor of disease progression or adverse vascular events are highly needed.

Inflammation markers and their trajectories after deep vein thrombosis in relation to risk of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT). OBJECTIVE: In the BioSOX study, we investigated whether inflammation markers predict the risk of PTS after DVT. METHODS: We measured C-reactive protein (CRP), ICAM-1, interleukin (IL)-6, and IL-10, at baseline, and 1 month and 6 months after a first proximal DVT, among 803 participants in the SOX trial. Participants were prospectively followed for 24 months for development of PTS. RESULTS: Median CRP levels at 1 month, ICAM-1 levels at baseline, 1 month and 6 months, IL-6 levels at 1 month and 6 months and IL-10 levels at 6 months were higher in patients who developed PTS than in those who did not. Multivariable regression with the median as a cutoff showed risk ratios (RRs) for PTS of 1.23 (95% confidence interval [CI] 1.05-1.45) and 1.25 (95% CI 1.05-1.48) for ICAM-1 at 1 month and 6 months, respectively, and 1.27 (95% CI 1.07-1.51) for IL-10 at 6 months. Quartile-based analysis demonstrated a dose-response association between ICAM-1 and PTS. ICAM-1 and IL-10 were also associated with PTS severity. Analysis of biomarker trajectories after DVT demonstrated an association between the highest-trajectory group of ICAM-1 and PTS. CONCLUSIONS: In this prospective study, ICAM-1 over time was most consistently associated with the risk of PTS. Further study is required to confirm these findings and assess their potential clinical relevance.

Vein grafts to augment flexor tendon repairs: a biomechanical study on strength and gap resistance.

The ultimate tensile repair strength and gap formation of the pig extensor tendons repaired with a standard 4-strand Savage with epitendinous suture repair, was compared with a new technique of adding a vein sleeve. Force and displacement data were recorded, and video images during linear cyclic loading up to failure. At 35 N, video-graphic observation detected significantly smaller gap lengths in the standard and vein repair specimens compared with standard repair specimens (p = 0.047). The incidence of 3 mm gaps between the repaired tendon ends in the standard repair group was 20 %, but no 3 mm gaps were seen in the standard and vein specimens. The addition of a vein sleeve increased the ultimate tensile strength of the standard repair from 50.4 N (4.5) to 55.4 N (4.5); this was statistically significant (p = 0.03). This study demonstrated that the addition of a vein graft prevented gap formation and increased ultimate tensile strength of tendon repair.

Graduated compression stockings to treat acute leg pain associated with proximal DVT. A randomised controlled trial.

Acute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30-40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.