BACKGROUND: Low anterior resection syndrome (LARS) is pragmatically defined as disordered bowel function after rectal resection leading to a detriment in quality of life. This broad characterization does not allow for precise estimates of prevalence. The LARS score was designed as a simple tool for clinical evaluation of LARS. Although the LARS score has good clinical utility, it may not capture all important aspects that patients may experience. The aim of this collaboration was to develop an international consensus definition of LARS that encompasses all aspects of the condition and is informed by all stakeholders. METHODS: This international patient-provider initiative used an online Delphi survey, regional patient consultation meetings and an international consensus meeting. Three expert groups participated: patients, surgeons and other health professionals from five regions (Australasia, Denmark, Spain, Great Britain and Ireland, and North America) and in three languages (English, Spanish and Danish). The primary outcome measured was the priorities for the definition of LARS. RESULTS: Three hundred and twenty-five participants (156 patients) registered. The response rates for successive rounds of the Delphi survey were 86%, 96% and 99%. Eighteen priorities emerged from the Delphi survey. Patient consultation and consensus meetings refined these priorities to eight symptoms and eight consequences that capture essential aspects of the syndrome. Sampling bias may have been present, in particular, in the patient panel because social media was used extensively in recruitment. There was also dominance of the surgical panel at the final consensus meeting despite attempts to mitigate this. CONCLUSIONS: This is the first definition of LARS developed with direct input from a large international patient panel. The involvement of patients in all phases has ensured that the definition presented encompasses the vital aspects of the patient experience of LARS. The novel separation of symptoms and consequences may enable greater sensitivity to detect changes in LARS over time and with intervention.

Background The purpose of this randomized controlled trial was to compare the performance of 3 total knee joint replacement (TKJR) designs 6 months after the surgery. Methods Patients were recruited between March 2015 and March 2018. Patients with osteoarthritis consented for TKJR were randomly allocated to a medial stabilized (MS), cruciate retaining (CR), or posterior stabilized (PS) design. Primary outcome measures were self-reported improvement in pain and function 6 months after TKJR, using the Oxford Knee Score. Secondary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index, Veterans RAND 12-item Health Survey, Knee Society Score 2011, Timed Up and Go test, and Six-Minute Walk Test. Twelve-month outcomes were also measured. Results Ninety participants enrolled, 83 were randomized: PS (n = 26), CR (n = 28), and MS (n = 29) designs. One case withdrew before surgery: planned use of non-study implant; 7 did not complete all outcome measures. No 6-month between-group difference was observed for the primary outcome. A 6-month difference was observed in Knee Society Score 2011 Satisfaction: MS favored over CR and PS. Clinically meaningful 12-month differences in Western Ontario and McMaster Universities Osteoarthritis Index Pain, Function, and Global Subscales were observed: MS favored over CR. Twelve-month differences occurred in Veterans RAND 12-item Health Survey mental well-being, favoring MS and PS over CR. Conclusion MS prosthesis can be expected to yield similar clinical and functional outcomes to PS and CR designs 6 months after TKJR, and patients were more satisfied with their outcome. Compared with CR, patients with MS prosthesis also reported superior pain, function, and quality-of-life outcomes at 12 months.

BACKGROUND: Health care systems are increasingly looking to mobile device technologies (mobile health) to improve patient experience and health outcomes. SecondEars is a smartphone app designed to allow patients to audio-record medical consultations to improve recall, understanding, and health care self-management. Novel health interventions such as SecondEars often fail to be implemented post pilot-testing owing to inadequate user experience (UX) assessment, a key component of a comprehensive implementation strategy. OBJECTIVE: This study aimed to pilot the SecondEars app within an active clinical setting to identify factors necessary for optimal implementation. Objectives were to (1) investigate patient UX and acceptability, utility, and satisfaction with the SecondEars app, and (2) understand health professional perspectives on issues, solutions, and strategies for effective implementation of SecondEars. METHODS: A mixed methods implementation study was employed. Patients were invited to test the app to record consultations with participating oncology health professionals. Follow-up interviews were conducted with all participating patients (or carers) and health professionals, regarding uptake and extent of app use. Responses to the Mobile App Rating Scale (MARS) were also collected. Interviews were analyzed using interpretive descriptive methodology; all quantitative data were analyzed descriptively. RESULTS: A total of 24 patients used SecondEars to record consultations with 10 multidisciplinary health professionals. In all, 22 of these patients used SecondEars to listen to all or part of the recording, either alone or with family. All 100% of patient participants reported in the MARS that they would use SecondEars again and recommend it to others. A total of 3 themes were identified from the patient interviews relating to the UX of SecondEars: empowerment, facilitating support in cancer care, and usability. Further, 5 themes were identified from the health professional interviews relating to implementation of SecondEars: changing hospital culture, mitigating medico-legal concerns, improving patient care, communication, and practical implementation solutions. CONCLUSIONS: Data collected during pilot testing regarding recording use, UX, and health professional and patient perspectives will be important for designing an effective implementation strategy for SecondEars. Those testing the app found it useful and felt that it could facilitate the benefits of consultation recordings, along with providing patient empowerment and support. Potential issues regarding implementation were discussed, and solutions were generated. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry ACTRN12618000730202; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373915&isClinicalTrial=False.

Purpose: Corneal injury that occurs after burning with alkali initiates wound-healing processes, including inflammation, neovascularization, and fibrosis. Excessive reactions to injury can reduce corneal transparency and thereby compromise vision. The NADPH oxidase (Nox) enzyme complex is known to be involved in cell signaling for wound-healing angiogenesis, but its role in corneal neovascularization has been little studied. Methods: The center corneas of wild-type and Nox4 knockout (KO) mice were injured with 3 µL 1 M NaOH, while the contralateral corneas remained untouched. On day 7, mRNA expression levels of NADPH oxidase isoforms, the proangiogenic factors VEGF-A and TGFβ1, and proinflammatory genes ICAM-1 and VCAM-1 were determined. Corneal neovascularization and fibrosis were visualized using PECAM-1 antibody and picrosirius red staining, respectively, on the same day. Results: Expressions of both Nox2 and Nox4 gene isoforms as well as the above genes were markedly increased in the injured corneas at 7 days. Injured corneas showed neovascularization and fibrosis as well as an increase in clinical opacity score. All responses stimulated by alkali burn were abrogated in Nox4 KO mice. Conclusions: Nox4 could be a new target to treat pathologic corneal wound-healing responses and such targeting might prevent blindness caused by burn injuries.

BACKGROUND: Not meeting functional performance criteria increases reinjury risk after ACL reconstruction (ACLR), but the implications for osteoarthritis are not well known. OBJECTIVE: To determine if poor functional performance post-ACLR is associated with risk of worsening early osteoarthritis features, knee symptoms, function and quality of life (QoL). METHODS: Seventy-eight participants (48 men) aged 28±15 years completed a functional performance test battery (three hop tests, one-leg-rise) 1 year post-ACLR. Poor functional performance was defined as <90% limb symmetry index (LSI) on each test. At 1 and 5 years, MRI, Knee injury Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) subjective form were completed. Primary outcomes were: (i) worsening patellofemoral and tibiofemoral MRI-osteoarthritis features (cartilage, bone marrow lesions (BMLs) and meniscus) and (ii) change in KOOS and IKDC scores, between 1 and 5 years. RESULTS: Only 14 (18%) passed (≥90% LSI on all tests) the functional test battery. Poor functional performance on the battery (all four tests <90% LSI) 1 year post-ACLR was associated with 3.66 times (95% CI 1.12 to 12.01) greater risk of worsening patellofemoral BMLs. A triple-crossover hop <90% LSI was associated with 2.09 (95% CI 1.15 to 3.81) times greater risk of worsening patellofemoral cartilage. There was generally no association between functional performance and tibiofemoral MRI-osteoarthritis features, or KOOS/IKDC scores. CONCLUSION: Only one in five participants met common functional performance criteria (≥90% LSI all four tests) 1 year post-ACLR. Poor function on all four tests was associated with a 3.66 times increased risk of worsening patellofemoral BMLs, and generally not associated with decline in self-reported outcomes.

Improving outcomes for uncommon tumours such as anal cancer can be challenging. Evolution of care tends to be incremental rather than transformative and identifying the specific factors facilitating improvement can be difficult. Outcome from specialist units may be better than that demonstrated in trials, posing challenges for development of future trials.

Reciprocal interactions between prostate epithelial cells and their adjacent stromal microenvironment not only are essential for tissue homeostasis but also play a key role in tumor development and progression. Malignant transformation is associated with the formation of a reactive stroma where cancer-associated fibroblasts (CAFs) induce matrix remodeling and thereby provide atypical biochemical and biomechanical signals to epithelial cells. Previous work has been focused on the cellular and molecular phenotype as well as on matrix stiffness and remodeling, providing potential targets for cancer therapeutics. So far, biomechanical changes in CAFs and adjacent epithelial cells of the prostate have not been explored. Here, we compared the mechanical properties of primary prostatic CAFs and patient-matched non-malignant prostate tissue fibroblasts (NPFs) using atomic force microscopy (AFM) and real-time deformability cytometry (RT-FDC). It was found that CAFs exhibit an increased apparent Young's modulus, coinciding with an altered architecture of the cytoskeleton compared with NPFs. In contrast, co-cultures of benign prostate epithelial (BPH-1) cells with CAFs resulted in a decreased stiffness of the epithelial cells, as well as an elongated morphological phenotype, when compared with co-cultures with NPFs. Moreover, the presence of CAFs increased proliferation and invasion of epithelial cells, features typically associated with tumor progression. Altogether, this study provides novel insights into the mechanical interactions between epithelial cells with the malignant prostate microenvironment, which could potentially be explored for new diagnostic approaches.

Adipose tissue is a rich source of stem cells, which are reported to represent 2% of the stromal vascular fraction (SVF). The infrapatellar fat pad (IFP) is a unique source of tissue, from which human adipose-derived stem cells (hADSCs) have been shown to harbour high chondrogenic potential. This review aims to calculate, based on the literature, the culture time needed before an average knee articular cartilage defect can be treated using stem cells obtained from arthroscopically or openly harvested IFP. Firstly, a systematic literature review was performed to search for studies that included the number of stem cells isolated from the IFP. Subsequent analysis was conducted to identify the amount of IFP tissue harvestable, stem cell count and the overall yield based on the harvesting method. We then determined the minimum time required before treating an average-sized knee articular cartilage defect with IFP-derived hADSCs by using our newly devised equation. The amount of fat tissue, the SVF cell count and the stem cell yield are all lower in arthroscopically harvested IFP tissue compared to that collected using arthrotomy. As an extrapolation, we show that an average knee defect can be treated in 20 or 17 days using arthroscopically or openly harvested IFP-derived hADSCs, respectively. In summary, the systematic review conducted in this study reveals that there is a higher amount of fat tissue, SVF cell count and overall yield (cells/volume or cells/gram) associated with open (arthrotomy) compared to arthroscopic IFP harvest. In addition to these review findings, we demonstrate that our novel framework can give an indication about the culture time needed to scale up IFP-derived stem cells for the treatment of articular cartilage defects based on harvesting method.

PURPOSE OF REVIEW: We review the literature on hip fracture mechanics and models of hip strain during exercise to postulate the exercise regimen for best promoting hip strength. RECENT FINDINGS: The superior neck is a common location for hip fracture and a relevant exercise target for osteoporosis. Current modelling studies showed that fast walking and stair ambulation, but not necessarily running, optimally load the femoral neck and therefore theoretically would mitigate the natural age-related bone decline, being easily integrated into routine daily activity. High intensity jumps and hopping have been shown to promote anabolic response by inducing high strain in the superior anterior neck. Multidirectional exercises may cause beneficial non-habitual strain patterns across the entire femoral neck. Resistance knee flexion and hip extension exercises can induce high strain in the superior neck when performed using maximal resistance loadings in the average population. Exercise can stimulate an anabolic response of the femoral neck either by causing higher than normal bone strain over the entire hip region or by causing bending of the neck and localized strain in the superior cortex. Digital technologies have enabled studying interdependences between anatomy, bone distribution, exercise, strain and metabolism and may soon enable personalized prescription of exercise for optimal hip strength.