Endoprosthetic reconstruction for lower extremity soft tissue sarcomas with bone involvement.

BACKGROUND AND OBJECTIVES: Bone resection and endoprosthetic reconstruction (EPR) in the setting of soft tissue sarcoma (STS) management is rare and incurs unique challenges. We aim to report on the surgical and oncological outcomes of this relatively previously undocumented cohort. METHODS: This is a single-center retrospective review of prospectively collected data for patients who required EPRs following resection of STSs of the lower extremity. Following inclusion criteria, we assessed 29 cases of EPR for primary STS of the lower limb. RESULTS: The mean age was 54 years (range 18-84). Of the 29 patients, there were 6 total femur, 11 proximal femur, 4 intercalary, and 8 distal femur EPRs. Fourteen of 29 patients (48%) underwent re-operations for surgical complications, with 9 relating to infection (31%). When a matched cohort analysis was performed comparing our cohort to STSs that did not necessitate EPR, a reduced rate of overall survival and metastasis-free survival was found in those requiring EPR. CONCLUSION: This series identifies a high rate of complication from EPRs performed for STS. Patients should be cautioned about the high rate of infection, surgical complications, and lower overall survival in this setting.

Unpacking Relational Dignity: In Pursuit of an Ethic of Care for Outdoor Therapies.

Dignity is a universal principle that requires us to treat every person as having worth beyond who a particular person is or what they do. Dignity is a complex and sometimes contested idea, that at times can be compromised in health care and allegedly also within the practice of outdoor therapy. Outdoor therapies comprise a range of therapeutic approaches including nature-based therapy, adventure therapy, animal-assisted therapy, forest therapy, wilderness therapy, surf therapy, and more. Within the literature of outdoor therapies there has been limited research on ethics related to common understandings of care concepts such as relational dignity and human rights. The aim of this paper is therefore to unravel briefly whether dignity in general, and relational qualities of dignified care more particularly, might be a useful concept to apply in order to support an ethical practice in outdoor therapies.

Structuring Poverty: How Racism Shapes Child Poverty and Child and Adolescent Health.

Black, Native, and Latinx populations represent the racial and ethnic groups most impacted by poverty. This unequal distribution of poverty must be understood as a consequence of policy decisions-some that have sanctioned violence and others that have created norms-that continue to shape who has access to power, resources, rights, and protections. In this review, we draw on scholarship from multiple disciplines, including pediatrics, public health, environmental health, epidemiology, social and biomedical science, law, policy, and urban planning to explore the central question-What is the relationship between structural racism, poverty, and pediatric health? We discuss historic and present-day events that are critical to the understanding of poverty in the context of American racism and pediatric health. We challenge conventional paradigms that treat racialized poverty as an inherent part of American society. We put forth a conceptual framework to illustrate how white supremacy and American capitalism drive structural racism and shape the racial distribution of resources and power where children and adolescents live, learn, and play, ultimately contributing to pediatric health inequities. Finally, we offer antipoverty strategies grounded in antiracist practices that contend with the compounding, generational impact of racism and poverty on heath to improve child, adolescent, and family health.

Nature's Role in Outdoor Therapies: An Umbrella Review.

Objective: To report on the role of nature in outdoor therapies through review and summary of existing systematic and meta-analytic reviews in an effort to articulate a theoretical framework for practice. Materials and methods: An umbrella review was conducted following systematic protocols PRISMA guidelines. Results: Fourteen studies met the inclusion criteria and represented five self-identified approaches: nature-based therapies, forest therapy, horticultural therapy, wilderness therapy, and adventure therapy. Clear and comprehensive descriptions of theory, program structure, and activity details with causal links to outcomes were mostly absent. Conclusions: A rigorous and determined program of research is required in order to explicit in-depth theories of change in outdoor therapies. Conversely, or maybe concurrently, a holistic theory of integrated relatedness may be developed as a parallel expression of support for nature in therapy while the explanatory science catches up.

Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in Psoriasis: A Prospective Cohort Study.

OBJECTIVES: This study hypothesized that there is an association between chronic stress (as indexed by resting amygdalar activity [AmygA]), hematopoietic system activity (HMPA), and subclinical cardiovascular indexes (aortic vascular inflammation [VI] and noncalcified coronary plaque burden [NCB]) in psoriasis (PSO). The study also hypothesized that treatment of PSO would improve these parameters. BACKGROUND: PSO is a stress-related chronic inflammatory condition that is associated with increased prevalence of subclinical cardiovascular disease (CVD). In individuals without PSO, stress has been linked to CVD through a serial biological pathway that involves the amygdala, hematopoietic tissues, and atherosclerotic plaques. METHODS: A total of 164 consecutive patients with PSO and 47 healthy volunteers underwent 18-fluorodeoxyglucose positron emission tomography/computed tomography scans for assessment of AmygA, HMPA, and VI, as well as coronary computed tomography angiography scans for quantifying NCB. Furthermore, a consecutive subset of 30 patients with severe PSO (Psoriasis Area Severity Index Score >10) were followed at 1 year to assess the relationship between skin disease improvement and AmygA, HMPA, VI, and NCB. RESULTS: The PSO cohort was middle-aged (mean age: 50 years), had low cardiovascular risk (Framingham risk score: median: 3) and had mild to moderate PSO activity (median Psoriasis Area Severity Index Score: 5.6). AmygA was higher in patients with PSO compared to volunteer participants. AmygA was associated with HMPA (bone marrow activity: ß = 0.20, p = 0.01) and subclinical CVD (VI: ß = 0.31, p < 0.001; NCB: ß = 0.27, p < 0.001) The AmygA-CVD association was in part mediated by HMPA (VI: 20.9%, NCB: 36.7%). Following 1 year of PSO treatment in those with severe disease, improvement in skin disease was accompanied by a reduction in AmygA, bone marrow activity, and VI, with no progression of NCB. CONCLUSIONS: In PSO, a chronic inflammatory disease state, AmygA, which is a manifestation of chronic stress, substantially contributes to the risk of subclinical CVD. Additional studies that use psychometric measures of stress are required to explore therapeutic impact.

Association Between Soluble Lectinlike Oxidized Low-Density Lipoprotein Receptor-1 and Coronary Artery Disease in Psoriasis.

Importance: Psoriasis, a chronic inflammatory skin disease associated with accelerated noncalcified coronary burden (NCB) by coronary computed tomography angiography (CCTA), accelerates lipoprotein oxidation in the form of oxidized modified lipoproteins. A transmembrane scavenger receptor for these oxidized modified lipoproteins is lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1), which has been reported to be associated with coronary artery disease. It is unknown whether this receptor is associated with coronary artery disease in psoriasis. Objective: To assess the association between soluble LOX-1 (sLOX-1) and NCB in psoriasis over time. Design, Setting, and Participants: In a cohort study at the National Institutes of Health, 175 consecutive patients with psoriasis were referred from outpatient dermatology practices between January 1, 2013, and October 1, 2017. A total of 138 consecutively recruited patients with psoriasis were followed up at 1 year. Exposures: Circulating soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were measured blindly by field scientists running undiluted serum using an enzyme-linked immunosorbent assay. Main Outcomes and Measures: Coronary computed tomography angiography scans were performed to quantify NCB in all 3 major epicardial coronary arteries by a reader blinded to patient demographics, visit, and treatment status. Results: Among the 175 patients with psoriasis, the mean (SD) age was 49.7 (12.6) years and 91 were men (55%). The cohort had relatively low median cardiovascular risk by Framingham risk score (median, 2.0 [interquartile range (IQR), 1.0-6.0]) and had a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) suggestive of overweight profiles (29.6 [6.0]). Elevated sLOX-1 levels were found in patients with psoriasis compared with age- and sex-matched controls (median, 210.3 [IQR, 110.9-336.2] vs 83.7 [IQR, 40.1-151.0]; P < .001), and were associated with Psoriasis Area Severity Index (PASI) score (ß = 0.23; 95% CI, 0.082-0.374; P = .003). Moreover, sLOX-1 was associated with NCB independent of hyperlipidemia status (ß = 0.11; 95% CI, 0.016-0.200; P = .023), an association which persisted after adjusting for traditional cardiovascular risk factors, statin use, and biologic psoriasis treatment (ß = 0.10; 95% CI, 0.014-0.193; P = .03). At 1 year, in those who had clinical improvement in PASI (eg, >50% improvement), a reduction in sLOX-1 (median, 311.1 [IQR, 160.0-648.8] vs median, 224.2 [IQR, 149.1 - 427.4]; P = .01) was associated with a reduction in NCB (ß = 0.14; 95% CI, 0.028-0.246; P = .02). Conclusions and Relevance: Soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were elevated in patients with psoriasis and were associated with severity of skin disease. Moreover, sLOX-1 associated with NCB independent of hyperlipidemia status, suggesting that inflammatory sLOX-1 induction may modulate lipid-rich NCB in psoriasis. Improvement of skin disease was associated with a reduction of sLOX-1 at 1 year, demonstrating the potential role of sLOX-1 in inflammatory atherogenesis in psoriasis.

What are constructive anxiety levels in wilderness therapy? An exploratory pilot study.

BACKGROUND AND PURPOSE: Participant state anxiety in outdoor therapeutic practices continues to raise many questions. To help inform this important topic we present and discuss the results of an exploratory pilot study on participant day-to-day state anxiety throughout a Norwegian wilderness therapy intervention. MATERIALS AND METHODS: Thirty-three adolescents from six groups completed a total of 251 state sections of the State-Trait Anxiety Inventory. RESULTS: On average, there was a slight decrease in state anxiety as the program progressed and a significant reduction in anxiety between the first and final days. The between-subject range was large, and boys reported significantly lower anxiety than did girls. CONCLUSION: In light of the results, we discuss general understandings of day-to-day state anxiety, gender differences, group differences, the perception of risk, and the relationship between perceived autonomy and state anxiety. The paper concludes with implications for the outdoor therapy field at large.

Neutrophil Subsets, Platelets, and Vascular Disease in Psoriasis.

Psoriasis is an inflammatory skin disease associated with increased cardiovascular risk and serves as a reliable model to study inflammatory atherogenesis. Because neutrophils are implicated in atherosclerosis development, this study reports that the interaction among low-density granulocytes, a subset of neutrophils, and platelets is associated with a noncalcified coronary plaque burden assessed by coronary computed tomography angiography. Because early atherosclerotic noncalcified burden can lead to fatal myocardial infarction, the low-density granulocyte-platelet interaction may play a crucial target for clinical intervention.

The NICE classification for 'Ultra-radical (extensive) surgery for advanced ovarian cancer' guidance does not meaningfully predict postoperative complications: a cohort study.

OBJECTIVE: To determine which descriptors of cytoreductive surgical extent in advanced ovarian cancer (AOC) best predict postoperative morbidity. DESIGN: Retrospective notes review. SETTING: A gynaecological cancer centre in the UK. POPULATION: Six hundred and eight women operated on for AOC over a period of 114 months at a tertiary cancer centre, between 16 August 2007 and 16 February 2017. METHODS: Outcome data were analysed by six approaches to classify the extent of surgery: standard/ultra-radical surgery; standard/radical/supra-radical surgery; presence/absence of gastrointestinal resections; low/intermediate/high surgical complexity score (SCS); presence of bowel anastomoses and/or diaphragmatic surgery; and the presence/absence of multiple bowel resections. MAIN OUTCOME MEASURES: Major (grades 3-5) postoperative morbidity and mortality. RESULTS: Forty-three (7.1%) patients experienced major complications. Grade-5 complications occurred in six patients (1.0%). Patients who underwent multiple bowel resections had a relative risk (RR) of 7.73 (95% confidence interval, 95% CI 3.92-15.26), patients with a high SCS had an RR of 6.12 (95% CI 3.25-11.52), patients with diaphragmatic surgery and gastrointestinal anastomosis had an RR of 5.57 (95% CI 2.65-11.72), patients with 'any gastrointestinal resection' had an RR of 4.69 (95% CI 2.66-8.24), patients with ultra-radical surgery had an RR of 4.65 (95% CI 2.26-8.79), and patients with supra-radical surgery had an RR of 4.20 (95% CI 2.35-7.51) of grades 3-5 morbidity, compared with patients undergoing standard surgery as defined by the National Institute for Health and Care Excellence (NICE) in the UK. No significant difference was seen in the rate of major morbidity between standard (6/59, 10.2%) and ultra-radical (9/81, 11.1%) surgery within the cohort who had intermediate complex surgery (P > 0.05). CONCLUSIONS: The numbers of procedures performed significantly correlate with major morbidity. The number of procedures performed better predicted major postoperative morbidity than the performance of certain 'high risk' procedures. We recommend using SCS to define a higher risk operation. NICE should re-evaluate the use of the term 'ultra-radical' surgery. TWEETABLE ABSTRACT: Multiple bowel resection is the best predictor of morbidity and is more predictive than 'ultra-radical surgery'.

Basal Spontaneous Firing of Rabbit Sinoatrial Node Cells Is Regulated by Dual Activation of PDEs (Phosphodiesterases) 3 and 4.

BACKGROUND: Spontaneous firing of sinoatrial node cells (SANCs) is regulated by cAMP-mediated, PKA (protein kinase A)-dependent (cAMP/PKA) local subsarcolemmal Ca2+ releases (LCRs) from RyRs (ryanodine receptors). LCRs occur during diastolic depolarization and activate an inward Na+/Ca2+ exchange current that accelerates diastolic depolarization rate prompting the next action potential. PDEs (phosphodiesterases) regulate cAMP-mediated signaling; PDE3/PDE4 represent major PDE activities in SANC, but how they modulate LCRs and basal spontaneous SANC firing remains unknown. METHODS: Real-time polymerase chain reaction, Western blot, immunostaining, cellular perforated patch clamping, and confocal microscopy were used to elucidate mechanisms of PDE-dependent regulation of cardiac pacemaking. RESULTS: PDE3A, PDE4B, and PDE4D were the major PDE subtypes expressed in rabbit SANC, and PDE3A was colocalized with α-actinin, PDE4D, SERCA (sarcoplasmic reticulum Ca2+ ATP-ase), and PLB (phospholamban) in Z-lines. Inhibition of PDE3 (cilostamide) or PDE4 (rolipram) alone increased spontaneous SANC firing by ≈20% (P<0.05) and ≈5% (P>0.05), respectively, but concurrent PDE3+PDE4 inhibition increased spontaneous firing by ≈45% (P<0.01), indicating synergistic effect. Inhibition of PDE3 or PDE4 alone increased L-type Ca2+ current (ICa,L) by ≈60% (P<0.01) or ≈5% (P>0.05), respectively, and PLB phosphorylation by ≈20% (P>0.05) each, but dual PDE3+PDE4 inhibition increased ICa,L by ≈100% (P<0.01) and PLB phosphorylation by ≈110% (P<0.05). Dual PDE3+PDE4 inhibition increased the LCR number and size (P<0.01) and reduced the SR (sarcoplasmic reticulum) Ca2+ refilling time (P<0.01) and the LCR period (time from action potential-induced Ca2+ transient to subsequent LCR; P<0.01), leading to decrease in spontaneous SANC cycle length (P<0.01). When RyRs were disabled by ryanodine and LCRs ceased, dual PDE3+PDE4 inhibition failed to increase spontaneous SANC firing. CONCLUSIONS: Basal cardiac pacemaker function is regulated by concurrent PDE3+PDE4 activation which operates in a synergistic manner via decrease in cAMP/PKA phosphorylation, suppression of LCR parameters, and prolongation of the LCR period and spontaneous SANC cycle length.

Of Dodo birds and common factors: A scoping review of direct comparison trials in adventure therapy.

BACKGROUND: Adventure therapy (AT) is a term that includes therapies such as wilderness therapy and adventure-based counseling. With growing empirical support for AT, the diversity of studies make it difficult to attribute outcomes to specific treatment factors. OBJECTIVES: Researchers explored whether AT, often perceived as an alternative therapy, works because of AT's unique components, or whether factors shared by all therapies were responsible. METHODS: A scoping review was undertaken utilizing a search of major databases, unpublished dissertations, and a hand search for direct comparison trials matching AT with another therapeutic intervention. RESULTS: 881 publications were identified. 105 quantitative studies were included following a title and abstract review. Only 13 met the full inclusion criteria. Little to no differences were found to isolate specific therapeutic factors. CONCLUSIONS: We discuss the implications of these results considering the movement toward evidence-based practice and recommend future research to eclipse our current understanding of AT.

Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis.

Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the human disease state, including presence of systemic inflammation, dyslipidemia, and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic phenotype with increased lipid uptake and foam cell formation, and also showed a 6-fold increase in cholesterol crystal formation. We generated a triple-genetic K14-RacV12-/+/Srb1-/-/ApoER61H/H mouse and confirmed psoriasis accelerates atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity was restored in macrophages, their proatherogenic phenotype reversed. We demonstrate that the K14-RacV12 murine model captures the cardiometabolic dysfunction and accelerates vascular disease observed in chronic inflammation and that skin inflammation induces a proatherosclerotic macrophage phenotype with impaired SOD2 function, which associated with accelerated atherogenesis.

Nature Elements and Fundamental Motor Skill Development Opportunities at Five Elementary School Districts in British Columbia.

The majority of Canadian children are not physically active enough for healthy development. School playgrounds are a primary location to promote physical activity and motor skill practice. The benefits of children's play in nature have also been highlighted, but few studies have evaluated children's access and exposure to nature for play on school grounds. This study examined children's access to nature on school grounds and the opportunities afforded by those natural elements for motor skill practice. RESULTS: Extensive naturescapes (multiple nature elements in one setting) were not common, and natural elements were limited, ranging from 1.97 to 5.71 elements/school. The most common element was a forested area (26.5% of all natural elements identified). In comparison to built structures, the number of natural elements was low. Some elements differed between school districts and appeared to be related to local geography and terrain (hilly, rocky terrain, tidal flats, etc.). Our assessment showed that naturescape elements afforded opportunities for the development of some key fundamental motor skills (FMS), specifically, locomotor and stability skills, but opportunities to develop manipulative skills were limited. To maximize potential FMS development, physical literacy, and psycho-social benefits, additional elements or more comprehensive multi-element naturescapes and facilitation (social or environmental) are recommended.

Benchmarking of surgical complications in gynaecological oncology: prospective multicentre study.

OBJECTIVE: To explore the impact of risk-adjustment on surgical complication rates (CRs) for benchmarking gynaecological oncology centres. DESIGN: Prospective cohort study. SETTING: Ten UK accredited gynaecological oncology centres. POPULATION: Women undergoing major surgery on a gynaecological oncology operating list. METHODS: Patient co-morbidity, surgical procedures and intra-operative (IntraOp) complications were recorded contemporaneously by surgeons for 2948 major surgical procedures. Postoperative (PostOp) complications were collected from hospitals and patients. Risk-prediction models for IntraOp and PostOp complications were created using penalised (lasso) logistic regression using over 30 potential patient/surgical risk factors. MAIN OUTCOME MEASURES: Observed and risk-adjusted IntraOp and PostOp CRs for individual hospitals were calculated. Benchmarking using colour-coded funnel plots and observed-to-expected ratios was undertaken. RESULTS: Overall, IntraOp CR was 4.7% (95% CI 4.0-5.6) and PostOp CR was 25.7% (95% CI 23.7-28.2). The observed CRs for all hospitals were under the upper 95% control limit for both IntraOp and PostOp funnel plots. Risk-adjustment and use of observed-to-expected ratio resulted in one hospital moving to the >95-98% CI (red) band for IntraOp CRs. Use of only hospital-reported data for PostOp CRs would have resulted in one hospital being unfairly allocated to the red band. There was little concordance between IntraOp and PostOp CRs. CONCLUSION: The funnel plots and overall IntraOp (≈5%) and PostOp (≈26%) CRs could be used for benchmarking gynaecological oncology centres. Hospital benchmarking using risk-adjusted CRs allows fairer institutional comparison. IntraOp and PostOp CRs are best assessed separately. As hospital under-reporting is common for postoperative complications, use of patient-reported outcomes is important. TWEETABLE ABSTRACT: Risk-adjusted benchmarking of surgical complications for ten UK gynaecological oncology centres allows fairer comparison.

Predictors of complications in gynaecological oncological surgery: a prospective multicentre study (UKGOSOC-UK gynaecological oncology surgical outcomes and complications).

BACKGROUND: There are limited data on surgical outcomes in gynaecological oncology. We report on predictors of complications in a multicentre prospective study. METHODS: Data on surgical procedures and resulting complications were contemporaneously recorded on consented patients in 10 participating UK gynaecological cancer centres. Patients were sent follow-up letters to capture any further complications. Post-operative (Post-op) complications were graded (I-V) in increasing severity using the Clavien-Dindo system. Grade I complications were excluded from the analysis. Univariable and multivariable regression was used to identify predictors of complications using all surgery for intra-operative (Intra-op) and only those with both hospital and patient-reported data for Post-op complications. RESULTS: Prospective data were available on 2948 major operations undertaken between April 2010 and February 2012. Median age was 62 years, with 35% obese and 20.4% ASA grade ⩾3. Consultant gynaecological oncologists performed 74.3% of operations. Intra-op complications were reported in 139 of 2948 and Grade II-V Post-op complications in 379 of 1462 surgeries. The predictors of risk were different for Intra-op and Post-op complications. For Intra-op complications, previous abdominal surgery, metabolic/endocrine disorders (excluding diabetes), surgical complexity and final diagnosis were significant in univariable and multivariable regression (P<0.05), with diabetes only in multivariable regression (P=0.006). For Post-op complications, age, comorbidity status, diabetes, surgical approach, duration of surgery, and final diagnosis were significant in both univariable and multivariable regression (P<0.05). CONCLUSIONS: This multicentre prospective audit benchmarks the considerable morbidity associated with gynaecological oncology surgery. There are significant patient and surgical factors that influence this risk.

Patient-reporting improves estimates of postoperative complication rates: a prospective cohort study in gynaecological oncology.

BACKGROUND: Most studies use hospital data to calculate postoperative complication rates (PCRs). We report on improving PCR estimates through use of patient-reporting. METHODS: A prospective cohort study of major surgery performed at 10 UK gynaecological cancer centres was undertaken. Hospitals entered the data contemporaneously into an online database. Patients were sent follow-up letters to capture postoperative complications. Grade II-V (Clavien-Dindo classification) patient-reported postoperative complications were verified from hospital records. Postoperative complication rate was defined as the proportion of surgeries with a Grade II-V postoperative complication. RESULTS: Patient replies were received for 1462 (68%) of 2152 surgeries undertaken between April 2010 and February 2012. Overall, 452 Grade II-V (402 II, 50 III-V) complications were reported in 379 of the 1462 surgeries. This included 172 surgeries with 200 hospital-reported complications and 231 with 280 patient-reported complications. All (100% concordance) 36 Grade III-V and 158 of 280 (56.4% concordance) Grade II patient-reported complications were verified on hospital case-note review. The PCR using hospital-reported data was 11.8% (172 out of 1462; 95% CI 11-14), patient-reported was 15.8% (231 out of 1462; 95% CI 14-17.8), hospital and verified patient-reported was 19.4% (283 out of 1462; 95% CI 17.4-21.4) and all data were 25.9% (379 out of 1462; 95% CI 24-28). After excluding Grade II complications, the hospital and patient verified Grade III-V PCR was 3.3% (48 out of 1462; 95% CI 2.5-4.3). CONCLUSION: This is the first prospective study of postoperative complications we are aware of in gynaecological oncology to include the patient-reported data. Patient-reporting is invaluable for obtaining complete information on postoperative complications. Primary care case-note review is likely to improve verification rates of patient-reported Grade II complications.