Effect of perceived injustice-targeted pain neuroscience education compared with biomedically focused education in breast cancer survivors: a study protocol for a multicentre randomised controlled trial (BCS-PI trial).

INTRODUCTION: Current treatments for pain in breast cancer survivors (BCSs) are mostly biomedically focused rather than biopsychosocially driven. However, 22% of BCSs with pain are experiencing perceived injustice, which is a known predictor for adverse pain outcomes and opioid prescription due to increased maladaptive pain behaviour. Educational interventions such as pain neuroscience education (PNE) are suggested to target perceived injustice. In addition, motivational interviewing can be an effective behavioural change technique. This trial aims to examine whether perceived injustice-targeted PNE with the integration of motivational interviewing is superior to biomedically focused pain education in reducing pain after 12 months in BCS with perceived injustice and pain. In addition, improvements in quality of life, perceived injustice and opioid use are evaluated, and a cost-effectiveness analysis will finally result in a recommendation concerning the use of perceived injustice-targeted PNE in BCSs with perceived injustice and pain. METHODS AND ANALYSIS: This two-arm multicentre randomised controlled trial will recruit female BCS (n=156) with pain and perceived injustice. Participants will be randomly assigned to perceived injustice-targeted PNE or biomedically focused pain education in each centre. Both interventions include an online session, an information leaflet and three one-to-one sessions. The primary outcome (pain), secondary outcomes (quality of life, perceived injustice and outcomes for cost-effectiveness analysis) and explanatory outcomes (pain phenotyping, sleep, fatigue and cognitive-emotional factors) will be assessed at baseline and at 0, 6, 12 and 24 months postintervention using self-reported questionnaires online. Treatment effects over time will be evaluated using linear mixed model analyses. Additionally, a cost-utility analysis will be done from a healthcare payer and societal perspective. ETHICS AND DISSEMINATION: The ethical agreement was obtained from the Main Ethics Committee (B.U.N.1432020000068) at the University Hospital Brussels and all other participating hospitals. Study results will be disseminated through presentations, conferences, social media, press and journals. TRIAL REGISTRATION NUMBER: NCT04730154.

Effects of tele-prehabilitation on clinical and muscular recovery in patients awaiting knee replacement: protocol of a randomised controlled trial.

BACKGROUND: The increasing prevalence of knee osteoarthritis and total knee arthroplasty (TKA) impose a significant socioeconomic burden in developed and developing countries. Prehabilitation (rehabilitation in the weeks immediately before surgery) may be crucial to prepare patients for surgery improving outcomes and reducing assistance costs. Moreover, considering the progress of telemedicine, candidates for TKA could potentially benefit from a tele-prehabilitation programme. We aim to evaluate the effects of a home-based tele-prehabilitation program for patients waiting for total knee replacement. METHODS AND ANALYSIS: Forty-eight male patients, aged 65-80, on a waiting list for TKA will be recruited and randomly assigned to the tele-prehabilitation intervention or control groups. Both groups will undergo the same 6-week exercise program (five sessions/week) and the same educational session (one per week). The tele-prehabilitation group will perform asynchronous sessions using a tablet, two accelerometers and a balance board (Khymeia, Padova, Italy), while the control group will use a booklet. The Western Ontario and McMaster Universities Osteoarthritis Index Questionnaire, at the end of the prehabilitation, will be the primary outcome. Secondary outcomes will include self-reported outcomes, performance tests and change in expressions of blood and muscle biomarkers. Ten healthy subjects, aged 18-30, will be also recruited for muscle and blood samples collection. They will not undergo any intervention and their data will be used as benchmarks for the intervention and control groups' analyses. ETHICS AND DISSEMINATION: This randomised controlled trial will be conducted in accordance with the ethical principles of the Declaration of Helsinki. This study has been approved by the Ethics Committee of Vita-Salute San Raffaele University (Milan, Italy. No. 50/INT/2022). The research results will be published in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05668312.

Perceived Injustice in Cancer Survivors: Population-Specific Cut-Off Score and Relations with Personal Factors, Symptoms and Quality of Life-A Cross-Sectional Study.

Fatigue and pain are the most common side effects impacting quality of life (QoL) in cancer survivors. Recent insights have shown that perceived injustice (PI) can play a substantial role in these side effects, but research on cancer survivors is scarce. Furthermore, guidelines for recognizing clinically relevant levels of PI in cancer survivors are missing. The aims of this study are to provide a clinically relevant cut-off for PI and to explore relationships between personal characteristics, symptoms, and QoL with PI. This multicenter, cross-sectional study uses the Injustice Experience Questionnaire (IEQ), Numeric Pain Rating Scale (NPRS), Patient-Specific Complaints (PSC), Multidimensional Fatigue Index (MFI), and European Organization for Research and Treatment of Cancer QoL Questionnaire-C30 (EORTC-QLQ-C30). A clinical cut-off for PI was identified based on the 75th percentile of IEQ scores. Univariate and multivariate regressions explored the relationship between PI and personal characteristics (sex, age, cancer type, treatment type), symptoms (pain intensity, fatigue), and QoL (daily activity complaints, cancer-related QoL). Cancer survivors (n = 121) were included, and a cut-off of 20 was identified. Significant indirect associations were found between chemotherapy, NPRS, PSC, MFI, and EORTC-QLQ-C30 with PI. In the multivariate model, only MFI (B = 0.205; 95% CI: 0.125-0.018) and age (B = 0.086; 95% CI: -0.191-0.285) maintained a significant association with PI.

Exercise-induced effects on inflammatory markers and brain-derived neurotrophic factor in patients with knee osteoarthritis. A systematic review with meta-analysis.

Background: In the pathogenesis of knee osteoarthritis (KOA), inflammatory mediators play an important role. However, the precise underlying mechanism by which regular exercise therapy (ET) exert effects on the immune system in KOA patients is unknown. Objectives: The aim of this systematic review was to investigate the basal and acute effects of ET on inflammatory biomarkers and brain derived neurotrophic factor (BDNF) in KOA patients. Methods: PubMed, Web Of Science and PEDro were systematically searched for appropriate studies. If possible, a meta-analysis was performed or an approximation of the effect size (ES) was calculated. Risk of bias was scored using the Cochrane ROB 2.0 or ROBINS-tools. Results: Twenty-one studies involving 1374 participants were included. Fifteen articles focused on basal exercise effects, four on acute effects, and two on both. Biomarker analysis (n=18) was performed in synovial fluid (n=4) or serum/plasma (n=17). A meta-analysis demonstrated that basal CRP was reduced in KOA patients 6-18 weeks weeks after ET (MD: -0.17;95%CI[-0.31;-0.03]), while IL-6 (MD: 0.21;95%CI[-0.44;0.85]), and TNF-α (MD: -0.57;95%CI[-1.47;0.32]), levels did not significantly change. Also, sTNFR1/2 did not change significantly after ET. For other biomarkers, insufficient data were available to perform a meta-analysis. Nevertheless, a low degree of evidence was found for a decrease in IL-6 (ES:-0.596 & -0.259 & -0.513), an increase in sTNFR1 (ES:2.325), a decrease in sTNFR2 (ES:-0.997) and an increase in BDNF (ES:1.412). Locally, intra-articular IL-10 (ES:9.163) increased, and IL1ß (ES:-6.199) and TNF-α decreased (ES:-2.322) after ET. An acute exercise session elicited a myokine response (ES IL-6:0.314), and an increase in BDNF (no ES-data). No inflammatory effect (ES CRP:0.052; ES TNF-α:-0.019 & 0.081) following an acute bout of training was found. However, a single bout of exercise elicited a decrease in intra-articular IL-10 (no ES-data). Conclusion: ET can induce circulatory and intra-articular anti-inflammatory effects in patients with KOA. The antiinflammatory properties have important implications for informing these patients and clinicians about the underlying effects of ET.

Identification of Metabolic Factors and Inflammatory Markers Predictive of Outcome after Total Knee Arthroplasty in Patients with Knee Osteoarthritis: A Systematic Review.

OBJECTIVE: To identify metabolic factors and inflammatory markers that are predictive of postoperative total knee arthroplasty (TKA) outcome. METHOD: A systematic search of the existing literature was performed using the electronic databases PubMed, Web of Science and Embase until the 1st of August 2022. Studies that evaluated the influence of metabolic or inflammatory markers (I) on postsurgical outcome (O) in end-stage knee osteoarthritis patients awaiting primary TKA (P) were included in this review. RESULTS: In total, 49 studies were included. Risk of bias of the included studies was low for one study, moderate for 10 studies and high for the remaining 38 studies. Conflicting evidence was found for the influence of body mass index, diabetes, cytokine levels and dyslipidaemia on pain, function, satisfaction and quality of life at more than six months after TKA. CONCLUSIONS: Several limitations such as not taking into account known confounding factors, the use of many different outcome measures and a widely varying follow-up period made it challenging to draw firm conclusions and clinical implications. Therefore large-scaled longitudinal studies assessing the predictive value of metabolic and inflammatory factors pre-surgery in addition to the already evidenced risk factors with follow-up of one year after TKA are warranted.

The effect of psychologically informed practice with behavioural graded activity in cancer survivors: systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to determine the effectiveness of psychologically informed practice (PIP) with behavioural graded activity (BGA) compared to (1) waitlist controls (WLC), (2) other interventions (OI), (3) PIP alone or (4) BGA alone in cancer patients and survivors (CPaS). METHODS: PubMed, Web of Science and Embase were screened for randomised controlled trials encompassing BGA + PIP in CPaS. Effect sizes were inventoried for outcomes regarding physical activity (PA), quality of life (QoL) and debilitating symptoms (DS), which were assessed at four time points: post-intervention (PI), follow-up F1 (1 to 3 months), F2 (4 to 6 months) and F3 (> 6 months). The quality of the evidence was classified by the GRADE approach. RESULTS: Thirty-three studies were found eligible, comprising 4330 participants. Significant effects with low heterogeneity of PIP + BGA comparing to WLC were found for anxiety (SMD - 1.29 [-1.71; - 0.86]), depression (SMD - 0.79 [- 1.10; - 0.48]), functional impairment (SMD - 0.72 [- 0.95; - 0.50]), PA (self-reported: (SMD - 0.58 [- 0.84; - 0.32]) and objectively measured: (SMD - 0.51 [- 0.90; - 0.13])) and social impairment (SMD - 0.33 [- 0.58; - 0.08]). When comparing PIP + BGA to OI, fatigue (SMD - 0.35 [- 0.51; - 0.20]) and PA (SMD - 0.26 [- 0.41; - 0.11]) at PI, and fatigue (SMD - 0.34 [- 0.58; - 0.10]) at F1 were found significant with low heterogeneity. No significant effects were observed in the meta-analyses of studies comparing PIP + BGA to BGA or PIP alone. CONCLUSIONS: PIP with BGA has a favourable effect on DS, PA and QoL in CPaS when compared to non-behavioural interventions such as WLC, usual care and education. However, further research is needed on 'how' and 'when' PIP + BGA should be provided in cancer rehabilitation. IMPLICATIONS FOR CANCER SURVIVORS: PIP + BGA has the potential to facilitate CPaS to reach the recommended amount of PA and reduce DS.

Most amateur football teams do not implement essential components of neuromuscular training to prevent anterior cruciate ligament injuries and lateral ankle sprains.

PURPOSE: Neuromuscular training (NMT) is effective at reducing football injuries. The purpose of this study was to document the use of NMT to prevent anterior cruciate ligament injuries and lateral ankle sprains in adult amateur football and to identify barriers for using NMT. METHODS: A preseason and in-season online survey was completed by players and coaches of 164 football teams. The survey contained questions concerning injury history, type and frequency of NMT, and barriers when NMT was not used. RESULTS: A total of 2013 players (40% female) and 180 coaches (10% female) completed the preseason survey, whereas 1253 players and 140 coaches completed the in-season survey. Thirty-four percent (preseason) to 21% (in-season) of players used NMT, but only 8% (preseason) to 5% (in-season) performed adequate NMT (i.e. both balance and plyometric exercises, at least twice per week). In the subpopulation of players with an injury history, 12% (preseason) and 7% (in-season) performed adequate NMT. With respect to the coaches, only 5% (preseason) and 2% (in-season) implemented adequate NMT. Most important barriers for using NMT for both players and coaches were a lack of belief in its effectiveness, a lack of knowledge, the belief that stretching is sufficient, and not feeling the need for it. CONCLUSION: Most amateur football teams do not implement essential components of NMT. The results highlight the urgent need for developing strategies to enhance the adequate use of NMT in amateur football. LEVEL OF EVIDENCE: II.

Pain and Opioid Use in Cancer Survivors: A Practical Guide to Account for Perceived Injustice.

BACKGROUND: The presence of pain decreases survival rates in cancer. Pain management in clinical settings is often suboptimal and secondary to other cancer-related treatments, leaving many people undertreated. Opioid use is associated with side effects and decreased survival rate in cancer patients. Hence, there is an urgent need for considering factors such as perceived injustice that sustain post-cancer pain and trigger a behavioral pattern associated with opioid use. Injustice beliefs represent a maladaptive pattern of cognitive appraisal that may be a salient target for improving pain-related coping in these patients. Perceived injustice is associated with increased opioid prescription and prospectively predicted opioid use at 1-year follow-up, urging the need for targeted interventions to diminish perceived injustice. OBJECTIVES: Explain the importance of screening for perceived injustice in patients with pain following cancer treatment, its potential relevance for opioid abuse, and its potential impact on the management of pain following cancer. Also, prove clinicians with a clinical guide for an approach comprising of modified pain neuroscience education, motivational interviewing, and acceptance-based interventions to account for perceived injustice in patients having pain following cancer. STUDY DESIGN: A narrative review, perspective and treatment manual. SETTING: Several universities, a university of applied science department, a university hospital, and a private clinic (i.e., transdisciplinary pain treatment center). METHODS: Patients were cancer survivors with pain. Intervention included modified pain neuroscience education, motivational interviewing, and acceptance-based interventions. Measurements were taken through the Injustice Experience Questionnaire (IEQ). RESULTS: The IEQ can be used to assess perceived injustice in a valid way. Education about pain, including discussing perceived injustice, should be the first part of the management of pain in cancer survivors. In order to obtain the often-required behavioral change towards a more adaptive lifestyle, motivational interviewing can be used. To thoroughly tackle perceived injustice in patients having pain following cancer, special emphasis should be given to the individual reasons patients identify for experiencing (continued) pain and related symptoms. Pain acceptance should also be thoroughly addressed. LIMITATIONS: Clinical trials exploring the benefits, including cost-effectiveness, of such a multimodal approach in patients with pain following cancer treatment are needed. CONCLUSIONS: In light of its potential relevance for opioid abuse and potential impact on conservative management strategies, clinicians are advised to screen for perceived injustice in patients with pain following cancer treatment. Therapeutic targeting of perceived injustice can be done through an approach comprising of modified pain neuroscience education, motivational interviewing, and acceptance-based interventions.

The mediating effect of pain catastrophizing and perceived injustice in the relationship of pain on health-related quality of life in breast cancer survivors.

BACKGROUND: The importance of cognitive appraisals in the effectiveness of pain coping is well established. Two key variables in these appraisal processes are pain catastrophizing (PC) and perceived injustice (PI), which are known to increase the risk of long-term disability and aggravate the pain-related distress through maladaptive behavioral responses. However, to date, the mediating effects of these appraisals have not been examined concurrently in the breast cancer survivor (BCS) population, nor have they been related to health-related quality of life (HRQoL). METHODS: Using cross-sectional data from 110 BCS, structural path analyses were used to examine the mediating effects of PC and PI in the relationship of pain on the HRQoL in BCS. RESULTS: Results demonstrated a significant direct effect of pain and PI on HRQoL combined with a significant indirect effect through PI, but not through PC. An increase in pain is suggested to result in a decrease in quality of life. On the other hand, an increase in pain also is suggested to increase the PI. A similar relation with PC was not retained as significant. CONCLUSION: The relative salience of PI as a mediator of HRQoL underscores the fact that PI is not only understudied but also underappreciated and undertreated in the BCS population. The results of our study warrant replication across longitudinal studies but continue to expand upon the evidence of the multifactorial nature of pain coping in BCS.

Lifestyle and Pain following Cancer: State-of-the-Art and Future Directions.

This review discusses chronic pain, multiple modifiable lifestyle factors, such as stress, insomnia, diet, obesity, smoking, alcohol consumption and physical activity, and the relationship between these lifestyle factors and pain after cancer. Chronic pain is known to be a common consequence of cancer treatments, which considerably impacts cancer survivors' quality of life when it remains untreated. Improvements in lifestyle behaviour are known to reduce mortality, comorbid conditions (i.e., cardiovascular diseases, other cancer, and recurrence) and cancer-related side-effects (i.e., fatigue and psychological issues). An inadequate stress response plays an important role in dysregulating the body's autonomic, endocrine, and immune responses, creating a problematic back loop with pain. Next, given the high vulnerability of cancer survivors to insomnia, addressing and treating those sleep problems should be another target in pain management due to its capacity to increase hyperalgesia. Furthermore, adherence to a healthy diet holds great anti-inflammatory potential for relieving pain after cancer. Additionally, a healthy diet might go hand in hand with weight reduction in the case of obesity. Consuming alcohol and smoking have an acute analgesic effect in the short-term, with evidence lacking in the long-term. However, this acute effect is outweighed by other harms on cancer survivors' general health. Last, informing patients about the benefits of an active lifestyle and reducing a sedentary lifestyle after cancer treatment must be emphasised when considering the proven benefits of physical activity in this population. A multimodal approach addressing all relevant lifestyle factors together seems appropriate for managing comorbid conditions, side-effects, and chronic pain after cancer. Further research is needed to evaluate whether modifiable lifestyle factors have a beneficial influence on chronic pain among cancer survivors.

Prevalence and risk factors of sleep disturbances in breast cancersurvivors: systematic review and meta-analyses.

BACKGROUND: Breast cancer remains the most frequently diagnosed malignancy among women worldwide, with rising incidence numbers. In Belgium, one out of eight women will be diagnosed with breast cancer. Fortunately, 80% of those breast cancer patients will still be alive 10 years after diagnosis due to improvements in screening and treatment strategies. However, an important portion of the breast cancer survivors (BCS) will face side effects, such as sleep disturbances, long after treatment ends. It has been demonstrated that untreated insomnia in BCS negatively impacts mood, physical symptoms, pain sensitivity, fatigue, and quality of life. Furthermore, insomnia is increasingly considered an independent risk factor for future depression in BCS. The importance of understanding sleep disturbances in cancer populations has been highlighted and recognized as warranting further research. Therefore, the purpose of this systematic review was to determine the prevalence and the risk factors for the development of sleep disturbances in BCS. METHODS: PubMed, Web of Science, and PEDro were systematically screened for studies encompassing data regarding the prevalence or risk factors of sleep disturbances in BCS. If possible, meta-analyses were performed. Subgroup analyses were undertaken based on the methodological quality, study design, type of sleep disturbance, and the use of a measurement tool with strong psychometric properties to investigate significant heterogeneity (I2 > 50%) across studies. RESULTS: A total of 27 studies were found eligible. The pooled estimate for sleep disturbances prevalence is 0.40 (95% confidence interval (CI) = [0.29-0.52], I2 = 100%, p < 0.00001) and ranged from 0.14 (95% CI = [0.04-0.24]) to 0.93 (95% CI = [0.91-0.95]). Subgroup analyses did not reduce the heterogeneity among studies. Meta-analyses were performed for seven risk factors. Significant differences for the odds of developing sleep disturbances were found for hot flashes (pooled OR (ORp) 2.25, 95% CI = [1.64-3.08], I2 = 0%, p = 0.90), race (ORp 2.31, 95% CI = [1.56-3.42], I2 = 0%, p = 0.47), and menopause (ORp 1.84, 95% CI = [1.11-3.06], I2 = 0%, p = 0.70). After withdrawing the studies that did not rely on the use of a measurement tool with strong psychometric properties, pain (ORp 2.31, 95% CI = [1.36-3.92], I2 = 27%, p = 0.25), depressive symptoms (ORp 3.20, 95% CI [2.32-4.42], I2 = 0%, p = 0.63), and fatigue (ORp 2.82, 95% CI = [1.98-4.02], I2 = 0%, p = 0.60) became significant as well, with a substantial decrease of heterogeneity. CONCLUSION: Prevalence for sleep disturbances ranged from 0.14 to 0.93 with the vast majority of the studies investigating insomnia and sleep-wake disturbances. High heterogeneity makes it difficult to draw firm conclusions. Pain, depressive symptoms, hot flashes, fatigue, non-Caucasian race, and menopausal status were significantly associated with increased odds for developing sleep disturbances.

Chronic Pain in Breast Cancer Survivors: Nociceptive, Neuropathic, or Central Sensitization Pain?

INTRODUCTION: The differentiation between acute and chronic pain can be insufficient for appropriate pain management. The aim of this study was to evaluate the prevalence of the predominant pain type (nociceptive, neuropathic, or central sensitization [CS] pain) in breast cancer survivors (BCS) with chronic pain. The secondary aims were to examine (1) differences in health-related quality of life (HRQoL) between the different pain groups; and (2) the associations between patient-, disease-, and treatment-related factors and the different pain types. METHODS: To determine the prevalence of the predominant type of pain, a recently proposed classification system was used. BCS were asked to complete the VAS for pain, Douleur Neuropathique 4 Questionnaire, Margolis Pain Diagram, Central Sensitization Inventory, and Short Form 36 (SF-36). RESULTS: Ninety-one BCS participated, among whom 25.3% presented neuropathic pain, 18.7% nociceptive pain, and 15.4% CS pain. Mixed pain was found in 40.6%. A significant intergroup difference in HRQoL was found for SF-36 "general health" (P = 0.04). The odds for the presence of CS rather than nociceptive pain are 26 times higher in patients exposed to hormone therapy in comparison to the nonexposed (odds ratio 25.95, 95% confidence interval 1.33 to 504.37, P = 0.03). CONCLUSION: Neuropathic pain is most frequent in BCS. Strong associations were found between CS pain and hormone therapy.

Effect of Transcutaneous Electric Nerve Stimulation on Pain after Total Knee Arthroplasty: A Blind Randomized Controlled Trial.

Transcutaneous electric nerve stimulation (TENS) has proven to be effective for postsurgical pain relief. However, there is a lack of well-constructed clinical trials investigating the effect of TENS after total knee arthroplasty (TKA). In addition, previous investigations reported that low- and high-frequency TENSs produced analgesic tolerance after 4 or 5 days of treatment. The aim of this study is to explore the effect of burst TENS on pain during hospitalization after TKA and to investigate whether burst TENS produces analgesic tolerance after 4 or 5 days of treatment. This stratified, triple blind, randomized controlled trial was approved by the University Hospital Brussels. Sixty-eight subjects were screened for eligibility before surgery; 54 were found eligible and 53 were included in the analyses. Patients were allocated to either a burst TENS or sham burst TENS group. TENS was applied daily during continuous passive mobilization. Knee pain intensity, knee range of motion, and analgesic consumption were assessed daily. Patients received burst TENS (N = 25) or sham burst TENS (N = 28). No significant differences in knee pain intensity were found between the groups (p > 0.05). Within the TENS and the sham TENS groups, the difference in knee pain before and after treatment did not evolve over time (p > 0.05). This study found no effects of burst TENS compared with sham burst TENS on pain during hospitalization after TKA.

Risk factors of pain in breast cancer survivors: a systematic review and meta-analysis.

BACKGROUND: Breast cancer remains the number 1 lethal malignancy in women. With rising incidence and decreased mortality, the number of breast cancer survivors has increased. Consequently, sequelae, such as pain, are becoming more important. PURPOSE: The purpose of this study was to identify risk factors for the development of pain in breast cancer survivors. METHODS: PubMed and Web of Science were systematically screened for studies encompassing risk factors for the development of pain in breast cancer survivors. Meta-analyses were carried out for risk factors described in more than one article. Moderator analysis was performed in case of high heterogeneity (I 2 > 50%) across studies. RESULTS: Seventeen studies were found eligible. Meta-analyses were performed for 17 factors. Significant differences for the odds of developing chronic pain were found for BMI (overall OR: 1.34, 95%CI 1.08-1.67, p = 0.008), education (overall OR: 1.23, 95%CI 1.07-1.42, p = 0.005), lymphedema (overall OR: 2.58, 95%CI 1.93-3.46, p < 0.00001), smoking status (overall OR: 0.75, 95%CI 0.62-0.92, p = 0.005), axillary lymph node dissection (overall OR: 1.25, 95%CI 1.04-1.52, p = 0.02), chemotherapy (overall OR: 1.44, 95%CI 1.24-1.68, p < 0.00001), and radiotherapy (overall OR: 1.32, 95%CI 1.17-1.48, p < 0.00001). After performing moderator analyses for age, comorbidities, hormone therapy, and breast surgery, hormone therapy became a significant risk factor as well (overall OR: 1.33, 95%CI 1.15-1.54, p = 0.0001). CONCLUSION: BMI > 30, education < 12-13 years, lymphedema, not smoking, axillary lymph node dissection, chemotherapy, hormone therapy, and radiotherapy were significantly associated with higher odds for the development of chronic pain, with lymphedema being the biggest risk factor. Lack of uniformity across the studies in defining pain, follow-up, measurement tools, and cut-off values for the diagnosis of pain was noted, resulting in greater inter-study variability.

Prevalence of aromatase inhibitor-induced arthralgia in breast cancer: a systematic review and meta-analysis.

BACKGROUND: Although aromatase inhibitors have proven to be an effective treatment of hormone receptor-positive breast cancer in postmenopausal women, aromatase inhibitor-induced arthralgia (AIA) is an adverse event associated with low compliance with treatment. The aim of this literature study is to assess the prevalence of AIA and to provide an overview of significant predictors for the development of AIA. METHODS: A systematic review was conducted using PubMed, Cochrane Library and Web of Science. A meta-analysis was performed and heterogeneity has been investigated by moderator analyses. The meta-analysis was repeated with studies that were considered as best evidence, i.e. studies with an above-average score on the STROBE checklist. RESULTS: Twenty-one studies (13,177 participants) were included. Prevalence rates ranged from 0.200 to 0.737. Meta-analysis resulted in a pooled estimate of 0.459 (95% CI = [0.397-0.520) with a high heterogeneity (I 2 = 98%). Moderator analysis showed no differences regarding heterogeneity. Predictors for the development of AIA included a body mass index of 25-30 kg/m2 (OR = 0.33), taxane-based chemotherapy (OR = 4.08), stage III cancer (OR = 0.32) and a duration of menopause of 5-10 years (OR = 1.10) or >10 years (OR = 0.44-3.29) (An OR <1 indicates a predictor of lower risk of AIA). DISCUSSION: Despite the established benefits of AI, an important portion of the patients experiences AIA. More research is needed to investigate the efficacy of treatments such as exercise therapy for AIA.

Exercise in knee osteoarthritis: do treatment outcomes relate to bone marrow lesions? A randomized trial.

PURPOSE: Exercise is effective for reducing knee osteoarthritis (OA) pain but effect sizes vary widely. Moreover, not all knee OA patients perceive beneficial effects. Tailoring specific exercises to subgroups of knee OA patients may increase effectivity. Bone marrow lesions (BMLs) have been suggested as a criterion to define such subgroups. This study aimed to investigate whether BMLs' presence/absence is related to treatment outcomes in a group of knee OA patients who exercised for 18 weeks. METHODS: Subjects with symptomatic knee OA started a strength or walking exercise program. BMLs' presence at baseline was assessed. Pain was assessed before and after the intervention with the intermittent and constant osteoarthritis pain (ICOAP) questionnaire. Also the global perceived effect (GPE) on the patient's complaints was rated. RESULTS: Thirty-five patients (strength (N = 17) and walking (N = 18)) were analyzed for BMLs. BMLs were present in 25 (71%) knees. Five (14%) patients dropped out and 19 (54%) improved (GPE ≥5). All dropouts had BMLs, but no difference was seen between dropouts and retainers (p > 0.05). Pain scores did not differ between intervention groups (p > 0.05) or between patients with BMLs and without BMLs (p > 0.05). CONCLUSIONS: Pain scores and GPE was not different between knee OA patients with and without baseline BMLs in this sample. Implications for Rehabilitation Both walking and strengthening exercises are effective means of improving pain in patients with knee osteoarthritis. In a relatively small sample, this study shows that the presence or absence of subchondral bone marrow lesions, as seen on magnetic resonance images, is not related to treatment outcomes.

Anatomical Effects of Axillary Nodes Dissection on Rat Lymphatic System Model: Indocyanine Green Mapping and Dissection.

BACKGROUND: Axillary nodes dissection (AND) is an important risk factor for the appearance of breast cancer-related lymphedema (BCRL). The anatomy and pathophysiology leading to the development of BCRL after AND are not completely understood. Despite the existence of lymphedema models after AND, none of them were able to create lymphedemas without additional chemical inflammatory drugs or auxiliary physical techniques (radiotherapy). In this study, we aimed to describe the anatomical changes of AND on a rat's front leg before and after a new surgery technique. METHODS AND RESULTS: AND was performed on seven Wistar rats with a new, posterior surgical approach. Indocyanine green mapping was done before and after surgery to detect "normal and secondary superficial lymphatic pathways" of the operated rat's front legs. Twelve months after surgery, dissections were performed. Subcutaneous blue dye injection of the hand was used to observe superficial and deep lymphatic pathways. Postsurgery, an acute edema of arm and shoulder appeared and persisted for 14-21 days. However, none of the rats showed a chronic secondary lymphedema. In two cases, seromas also appeared. All rats showed substitution functional lymphatic pathways as perforating lymph vessels around the surgical sites. CONCLUSION: This is the first description of perforating lymph vessels as lymphatic substitution pathways after AND on rats. These results help to understand why a chronic secondary lymphedema could not be created in rats after AND without additional chemical or physical interventions.

The Influence of Joint Loading on Bone Marrow Lesions in the Knee: A Systematic Review With Meta-analysis.

BACKGROUND: Bone marrow lesions (BMLs) are considered as predictors of pain, disability, and structural progression of knee osteoarthritis. The relationship between knee loading and BMLs is not yet completely understood. PURPOSE: To summarize the available evidence regarding the relationship between joint loading and the prevalence and progression of BMLs in the tibiofemoral joint. STUDY DESIGN: Meta-analysis. METHODS: Three databases (PubMed, Web of Science, and The Cochrane Library) were systematically screened for studies encompassing BMLs and changes in knee loading. A methodological quality assessment was conducted, and a meta-analysis computing overall odds ratios (ORs) was performed where possible. RESULTS: A total of 29 studies involving 7641 participants were included. Mechanical loading was categorized as body weight and composition, compartmental load, structural lesion, and physical activity. High compartmental loads and structural lesions increased the risk for BMLs (overall ORs ranging from 1.56 [95% CI, 1.13-2.15] to 8.2 [95% CI, 4.4-15.1]; P = .006). Body weight increased the risk for BMLs to a lesser extent (overall OR, 1.03; 95% CI, 1.01-1.05; P = .007). Contradictory results for the effect of physical activity on BMLs were found. CONCLUSION: Augmented compartmental loads and structural lesions increased the risk of the presence or progression of BMLs. Body weight increased the risk for BMLs to a lesser extent. Contradictory results for the effect of physical activity on BMLs may be explained by a dose-response relationship, knee alignment, and structural lesions. CLINICAL RELEVANCE: It has been shown that unloading the knee temporarily may induce beneficial effects on osteoarthritis-related structural changes. Therefore, an early recognition of BMLs in the aging athlete's knee may provide information to counter the onset and aggravation of symptomatic knee osteoarthritis by reducing the knee load.