Inferior Outcomes for Patients Transferred Between Surgical Stages for Knee Periprosthetic Joint Infection.

BACKGROUND: Periprosthetic joint infection (PJI) in total knee arthroplasty may result in 2-stage revision surgery. There are limited data describing outcomes when the first stage is completed at an outside hospital and the patient is referred to a tertiary center. We hypothesized that patients have greater success when both surgeries occur at a single center. METHODS: There were 25 knee PJI patients who presented with an antibiotic spacer and had a minimum 2-year follow-up who were retrospectively identified at a single tertiary referral center from 2014 to 2021. A cohort matched for age, sex, body mass index, Elixhauser comorbidity measure, spacer type, infectious organism, and year of surgery was established with patients who had both stages completed at the investigating institution. Modified Delphi success criteria of no subsequent surgery or reinfection with any species were compared. RESULTS: The transferred group demonstrated a treatment success of 40% compared to 84% in the continuous group (P < .01). The transferred group was more likely to have an additional procedure between stages (44 versus 8%, P < .01), with a higher number of surgeries after primary total knee arthroplasty (4.8 versus 3.0, P < .01), between stages (1.4 versus 0.2, P < .01), and after second stage (0.8 versus 0.2, P = .03). The transferred group had longer durations between stages (20.1 versus 7.0 weeks, P < .01). CONCLUSION: Patients who have PJIs transferred between stages demonstrated higher treatment failure. Surgeons should consider transfer early with a goal of continuous management by a single institution.

Evaluating Exposure to VOCs and Naphthalene for Firefighters Wearing Different PPE Configurations through Measures in Air, Exhaled Breath, and Urine.

Firefighters are at an increased risk of cancer due to their occupational exposure to combustion byproducts, especially when those compounds penetrate the firefighter personal protective equipment (PPE) ensemble. This has led to questions about the impact of base layers (i.e., shorts vs. pants) under PPE ensembles. This study asked 23 firefighters to perform firefighting activities while wearing one of three different PPE ensembles with varying degrees of protection. Additionally, half of the firefighters unzipped their jackets after the scenario while the other half kept their jackets zipped for five additional minutes. Several volatile organic compound (VOC) and naphthalene air concentrations outside and inside of hoods, turnout jackets, and turnout pants were evaluated; biological (urinary and exhaled breath) samples were also collected. VOCs and naphthalene penetrated the three sampling areas (hoods, jackets, pants). Significant (p-value < 0.05) increases from pre- to post-fire for some metabolites of VOCs (e.g., benzene, toluene) and naphthalene were found. Firefighters wearing shorts and short sleeves absorbed higher amounts of certain compounds (p-value < 0.05), and the PPE designed with enhanced interface control features appeared to provide more protection from some compounds. These results suggest that firefighters can dermally absorb VOCs and naphthalene that penetrate the PPE ensemble.

Association between Physical Fitness and Cardiovascular Health in Firefighters.

Firefighters perform strenuous work in dangerous and unpredictable environments requiring optimal physical conditioning. The aim of this study was to investigate the association between physical fitness and cardiovascular health (CVH) in firefighters. This cross-sectional study systematically recruited 309 full-time male and female firefighters between the ages of 20 to 65 years in Cape Town, South Africa. Physical fitness was assessed using absolute (abV̇O2max) and relative oxygen consumption (relVO2max), grip and leg strength, push-ups and sit-ups, sit-and-reach for flexibility and lean body mass (LBM). CVH encompassed age, smoking, blood pressure (BP), blood glucose, lipid profile, body mass index, body fat percentage (BF%), and waist circumference. Linear regressions and logistic regressions were applied. Multivariable analysis indicated that relVO2max was associated with systolic BP (p < 0.001), diastolic BP (p < 0.001), non-fasting blood glucose (p < 0.001), and total cholesterol (p = 0.037). Poor CVH index was negatively associated with relV̇O2max (p < 0.001), leg strength (p = 0.019), and push-ups (p = 0.012). Furthermore, age was inversely associated with V̇O2max (p < 0.001), push-up and sit-up capacity (p < 0.001), and sit-and-reach (p < 0.001). BF% was negatively associated with abV̇O2max (p < 0.001), grip and leg strength (p < 0.001), push-ups (p = 0.008), sit-ups (p < 0.001), and LBM (p < 0.001). Cardiorespiratory fitness, muscular strength, and muscular endurance were significantly associated with a better overall CVH profile.

Silicone passive sampling used to identify novel dermal chemical exposures of firefighters and assess PPE innovations.

A plethora of chemicals are released into the air during combustion events, including a class of compounds called polycyclic aromatic hydrocarbons (PAHs). PAHs have been implicated in increased risk of cancer and cardiovascular disease, both of which are disease endpoints of concern in structural firefighters. Current commercially available personal protective equipment (PPE) typically worn by structural firefighters during fire responses have gaps in interfaces between the ensemble elements (e.g., hood and jacket) that allow for ingress of contaminants and dermal exposure. This pilot study aims to use silicone passive sampling to assess improvements in dermal protection afforded by a novel configuration of PPE, which incorporates a one-piece liner to eliminate gaps in two critical interfaces between pieces of gear. The study compared protection against parent and alkylated PAHs between the one-piece liner PPE and the standard configuration of PPE with traditional firefighting jacket and pants. Mannequins (n = 16) dressed in the PPE ensembles were placed in a Fireground Exposure Simulator for 10 min, and exposed to smoke from a combusting couch. Silicone passive samplers were placed underneath PPE at vulnerable locations near interfaces in standard PPE, and in the chamber air, to measure PAHs and calculate the dermal protection provided by both types of PPE. Silicone passive sampling methodology and analyses using gas chromatography with mass-spectrometry proved to be well-suited for this intervention study, allowing for the calculation and comparison of worker protection factors for 51 detected PAHs. Paired comparisons of the two PPE configurations found greater sum 2-3 ring PAH exposure underneath the standard PPE than the intervention PPE at the neck and chest, and at the chest for 4-7 ring PAHs (respective p-values: 0.00113, 0.0145, and 0.0196). Mean worker protection factors of the intervention PPE were also greater than the standard PPE for 98% of PAHs at the neck and chest. Notably, the intervention PPE showed more than 30 times the protection compared to the standard PPE against two highly carcinogenic PAHs, dibenzo[a,l]pyrene and benzo[c]fluorene. Nine of the detected PAHs in this study have not been previously reported in fireground exposure studies, and 26 other chemicals (not PAHs) were detected using a large chemical screening method on a subset of the silicone samplers. Silicone passive sampling appears to be an effective means for measuring dermal exposure reduction to fireground smoke, providing evidence in this study that reducing gaps in PPE interfaces could be further pursued as an intervention to reduce dermal exposure to PAHs, among other chemicals.

Effects of Cardiovascular Disease Risk Factors, Musculoskeletal Health, and Physical Fitness on Occupational Performance in Firefighters-A Systematic Review and Meta-Analysis.

Background: Firefighting is a strenuous occupation, which necessitates that firefighters stay in good physical condition and maintain adequate cardiovascular and musculoskeletal fitness to perform their duties with minimal health and safety risks. The aim of this review is to determine the effects of cardiovascular disease risk factors, musculoskeletal health, and physical fitness on the occupational performance of firefighters. Methods: PubMed/Medline, SCOPUS, Web of Science, EBSCOHost, and ScienceDirect were searched without time-restriction. The appraisal tool for cross-sectional studies and the Critical Appraisal Skills Programme toolkit were used to conduct the methodological assessment. Data were analyzed using Review Manager 5.3, and MedCalc® statistical software. Results: Age had a moderate effect on occupational performance (Z = 5.15, p < 0.001), whereas gender had a large effect size on occupational performance (Z = 4.24, p < 0.001). A significant moderate negative correlation was found between cardiorespiratory fitness and occupational performance (R = -0.584, p < 0.001). Significant low negative correlations were found between upper body endurance (R = -0.344, p < 0.001), abdominal endurance (R = -0.308, p < 0.001), grip strength (R = -0.421, p < 0.001), upper body strength (R = -0.318, p < 0.001), and lower body strength (R = -0.216, p = 0.020) and occupational performance. Conclusions: Aged firefighters with poor body composition and lower levels of physical fitness performed worse on all occupational performance tasks.

Cardiovascular Disease Risk Factors, Musculoskeletal Health, Physical Fitness, and Occupational Performance in Firefighters: A Narrative Review.

Introduction: Firefighting is a strenuous occupation that requires firefighters to be in peak physical condition. However, many firefighters have risk factors for cardiovascular disease, impaired musculoskeletal health, and are not physically fit for duty, which all negatively impact their occupational performance. Therefore, the aim of this review is to determine the relationship between cardiovascular disease risk factors, musculoskeletal health, physical fitness, and occupational performance in firefighters. Methods: The electronic databases PubMed, SCOPUS, and Web of Science were searched online via the library portal of the University of the Western Cape. Publications and grey literature between the years 2000 to present were used. In total, 2607 articles were identified; after the removal of duplicates 1188 articles were then screened, and were excluded for not meeting initial screening criteria. The remaining 209 full-text articles were screened based on the inclusion and exclusion criteria, where 163 articles were excluded. Only studies that were quantitative were included. This left 46 articles that were then finally included in the current narrative review. Results: The current literature indicated that significant relationships existed between cardiovascular risk factors, musculoskeletal health, physical fitness, and occupational performance. The results indicated firefighters who were aged, obese, physically inactive, cigarette smokers, and unfit were at the highest risk for cardiovascular and musculoskeletal health complications, and unsatisfactory occupational performance. Musculoskeletal health complications significantly affected occupational performance and work ability and were related to physical fitness of firefighters. Most cardiovascular risk factors were related to physical fitness, and all physical fitness parameters were related to occupational performance in firefighters. Conclusion: The overwhelming evidence in the current review established that physical fitness is related to occupational performance. However, the relationship between cardiovascular risk factors and musculoskeletal health in relation to occupational performance is less clear and still understudied. Significant gaps remain in the literature.

Clinical outcomes of brain metastasectomy from soft tissue and bone sarcomas: a systematic review.

BACKGROUND: Brain metastasis in sarcomas is associated with a poor prognosis. Data regarding prognostic factors and clinical outcomes of surgical resection of brain metastasis from sarcomas are limited. The objective of this systematic review was to evaluate survival outcomes post-brain metastasectomy for patients with soft tissue and bone sarcomas. METHODS: A systematic review was conducted examining survival outcomes among adults and children with soft tissue and bone sarcoma undergoing brain metastasectomy, in the English language from inception up to May 31, 2021. Two reviewers independently evaluated and screened the literature, extracted the data, and graded the included studies. The body of evidence was evaluated and graded according to the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies and the Joanna Briggs Institute Critical Appraisal Checklist for Case Series. Results were synthesized using descriptive methods. A meta-analysis was not possible due to the low quality and heterogeneity of studies. RESULTS: Ten studies published between 1994 and 2020 were included: three were retrospective cohort studies and seven were case series. 507 patients were included, of whom 269 underwent brain metastasectomy. The median follow-up period ranged between 14 and 29 months. The median survival period after metastasectomy ranged from 7 to 25 months. The most common prognostic factors associated with survival included presenting performance status, age, number of brain metastases, presence of lung metastases, and peri-operative radiation therapy administration. DISCUSSION: Although the level of evidence is low, retrospective studies support that brain metastasectomy can be performed with reasonable post-operative survival in selected individuals.

Hierarchy of contamination control in the fire service: Review of exposure control options to reduce cancer risk.

The international fire service community is actively engaged in a wide range of activities focused on development, testing, and implementation of effective approaches to reduce exposure to contaminants and the related cancer risk. However, these activities are often viewed independent of each other and in the absence of the larger overall effort of occupational health risk mitigation. This narrative review synthesizes the current research on fire service contamination control in the context of the National Institute for Occupational Safety and Health (NIOSH) Hierarchy of Controls, a framework that supports decision making around implementing feasible and effective control solutions in occupational settings. Using this approach, we identify evidence-based measures that have been investigated and that can be implemented to protect firefighters during an emergency response, in the fire apparatus and at the fire station, and identify several knowledge gaps that remain. While a great deal of research and development has been focused on improving personal protective equipment for the various risks faced by the fire service, these measures are considered less effective. Administrative and engineering controls that can be used during and after the firefight have also received increased research interest in recent years. However, less research and development have been focused on higher level control measures such as engineering, substitution, and elimination, which may be the most effective, but are challenging to implement. A comprehensive approach that considers each level of control and how it can be implemented, and that is mindful of the need to balance contamination risk reduction against the fire service mission to save lives and protect property, is likely to be the most effective.

Metastasectomy in Leiomyosarcoma: A Systematic Review and Pooled Survival Analysis.

This study assesses the survival in patients undergoing metastasectomy for leiomyosarcoma (LMS) and compares the outcomes by the site of metastasectomy. We conducted a systematic review and pooled survival analysis of patients undergoing metastasectomy for LMS. Survival was compared between sites of metastasectomy. We identified 23 studies including 573 patients undergoing metastasectomy for LMS. The pooled median survival was 59.6 months (95% CI 33.3 to 66.0). The pooled median survival was longest for lung metastasectomy (72.8 months 95% CI 63.0 to 82.5), followed by liver (34.8 months 95% CI 22.3 to 47.2), spine (14.1 months 95% CI 8.6 to 19.7), and brain (14 months 95% CI 6.7 to 21.3). Two studies compared the survival outcomes between patients who did, versus who did not undergo metastasectomy; both demonstrated a significantly improved survival with metastasectomy. We conclude that surgery is currently being utilized for LMS metastases to the lung, liver, spine, and brain with acceptable survival. Although low quality, comparative studies support a survival benefit with metastasectomy. In the absence of randomized studies, it is impossible to determine whether the survival benefit associated with metastasectomy is due to careful patient selection rather than a surgical advantage; limited data were included about patient selection.

Establishing a health profession: What oncology patient navigators can learn from the National Association of Community Health Workers.

Persons who identify as community health workers (CHWs) may hold other titles and/or certifications, including the title of patient navigator (PN). PN roles first emerged from Dr. Harold Freeman's initiative at Harlem Hospital as a strategy to reduce disparities in access to health care, whereas CHW roles extend beyond health systems and are predominantly found in community-based organizations and nonprofits. Although CHWs' origins in the United States predate those of PNs, the growth of CHWs' professional identity and national representation trails that of PNs despite evidence of CHWs' effectiveness since the 1960s. Barriers to progress have included a pattern of short-term and inequitable funding for CHW positions, a lack of employer support for participation in association business, and broad diversity in CHW roles and work settings. The National Association of Community Health Workers (NACHW) was launched in 2019 and built on earlier organizing efforts by multisector, multicultural CHWs and allies in the CHW section of the American Public Health Association and on efforts to create the American Association of Community Health Workers (2006-2009). Trends in health care financing, increasing calls for racial equity, and the coronavirus disease 2019 (COVID-19) pandemic have amplified the unique abilities and trust that CHWs apply to underresourced, marginalized, and multiethnic populations to address both the social determinants of health and health system access, cost, and quality. As a result, the NACHW has been at the forefront of efforts to improve federal funding for COVID responses, to sustain funding for CHWs and their organizations beyond the pandemic, and to drive equity in the rebuilding of public health infrastructure and the transformation of payment models and health systems. Lessons learned from this process that have implications for the oncology patient navigation field include the persistent need to reinforce the value of self-determination for the profession in matters of policy; the importance of actively cultivating unity among diverse cultural and practice groups within the profession; the essential roles of active volunteer leadership, early staffing, and substantial financial support over an extended startup period; the ongoing need for leadership development within a workforce with limited exposure to a professional association culture; the vital importance of ongoing efforts to collaborate with and build capacity among state-level CHW networks; and the value of opportunistic national collaborations in a rapidly evolving policy environment.

Metastasectomy in synovial sarcoma: A systematic review and meta-analysis.

BACKGROUND: Synovial sarcoma (SS) is a malignancy with high metastatic potential. The role of metastasectomy in SS is unclear, with limited data on prognostic factors and clinical outcomes. In this systematic review, we evaluate the survival outcomes post-metastasectomy for patients with SS. METHODS: A systematic review was undertaken following PRISMA guidelines. English studies reporting survival outcomes among adults and children with SS undergoing metastasectomy were evaluated. Databases were searched from inception to May 31, 2021, and included Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Two reviewers independently undertook literature evaluation and screening, data extraction and grading of studies. Risk of bias assessments utilized the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies and the Joanna Briggs Institute Critical Appraisal Checklist for Case Series. Qualitative data was summarized in descriptive format, and survival outcome data were assessed for meta-analysis. RESULTS: Thirteen retrospective studies, published between 1993 and 2017, were included, four were cohort studies, and nine were case series. A total of 598 patients with SS were included, of whom 462 had metastatic pulmonary disease, and 309 underwent metastasectomy. The median ages of the study cohorts ranged from 14 to 51 years. The median survival period after metastasectomy ranged from 21 to 80 months. Patients who underwent metastasectomy had a lower risk of mortality compared to those who did not (pooled HR 0.26 95% CI 0.14-0.49). The most common prognostic factors associated with survival included a disease-free interval of greater than 12 months and complete resection of the metastases. DISCUSSION: Although the level of evidence is low, retrospective studies support a clinical advantage for metastasectomy in selected patients with metastatic SS. FUNDING: This was not a funded study. REGISTRATION: This protocol has been registered within the international prospective register of systematic reviews (PROSPERO) database (registration ID: CRD42019126906).

Firefighters' urinary concentrations of VOC metabolites after controlled-residential and training fire responses.

INTRODUCTION: Firefighters are exposed to volatile organic compounds (VOCs) during structural fire responses and training fires, several of which (e.g., benzene, acrolein, styrene) are known or probable carcinogens. Exposure studies have found that firefighters can absorb chemicals like benzene even when self-contained breathing apparatus (SCBA) are worn, suggesting that dermal absorption contributes to potentially harmful exposures. However, few studies have characterized VOC metabolites in urine from firefighters. OBJECTIVES: We quantified VOC metabolites in firefighters' urine following live firefighting activity across two field studies. METHODS: In two separate controlled field studies, spot urine was collected before and 3 h after firefighters and firefighter students responded to simulated residential and training fires. Urine was also collected from instructors from the training fire study before the first and 3 h after the last training scenario for each day (instructors led three training scenarios per day). Samples were analyzed for metabolites of VOCs to which firefighters may be exposed. RESULTS: In the residential fire study, urinary metabolites of xylenes (2MHA), toluene (BzMA), and styrene (MADA) increased significantly (at 0.05 level) from pre- to post-fire. In the training fire study, MADA concentrations increased significantly from pre- to post-fire for both firefighter students and instructors. Urinary concentrations of benzene metabolites (MUCA and PhMA) increased significantly from pre- to post-fire for instructors, while metabolites of xylenes (3MHA+4MHA) and acrolein (3HPMA) increased significantly for firefighter students. The two highest MUCA concentrations measured post-shift from instructors exceeded the BEI of 500 µg/g creatinine. CONCLUSIONS: Some of the metabolites that were significantly elevated post-fire are known or probable human carcinogens (benzene, styrene, acrolein); thus, exposure to these compounds should be eliminated or reduced as much as possible through the hierarchy of controls. Given stringent use of SCBA, it appears that dermal exposure contributes in part to the levels measured here.

Association Between Atrial Fibrillation and Occupational Exposure in Firefighters Based on Self-Reported Survey Data.

Background Exposure to inhaled smoke, pollutants, volatile organic compounds, and polycyclic aromatic hydrocarbons in the firefighting environment has been associated with detrimental respiratory and cardiovascular effects, making firefighters a unique population with both personal and occupational risk factors for cardiovascular disease. Some of these exposures are also associated with development of atrial fibrillation. We aimed to study the association of atrial fibrillation and occupational exposure in firefighters. Methods and Results A cross-sectional survey was conducted between October 2018 and December 2019. Data were gathered electronically and stored in a secure REDCap database through Louisiana State University Health Shreveport. Firefighters who were members of at least 1 of 5 preselected professional organizations were surveyed via electronic links distributed by the organizations. The survey queried the number of fires fought per year as a measure of occupational exposure, as well as self-reported cardiovascular disease. A total of 10 860 active firefighters completed the survey, of whom 93.5% were men and 95.5% were aged ≤60 years. Firefighters who fought a higher number of fires per year had a significantly higher prevalence of atrial fibrillation (0-5 fires per year 2%, 6-10 fires per year 2.3%, 11-20 fires per year 2.7%, 21-30 fires per year 3%, 31 or more fires per year 4.5%; P<0.001). Multivariable logistic regression showed that a higher number of fires fought per year was associated with an increased risk of atrial fibrillation (odds ratio 1.14 [95% CI, 1.04-1.25]; P=0.006). Conclusions Firefighters may have an increased risk of atrial fibrillation associated with the number of fires they fight per year. Further clinical and translational studies are needed to explore causation and mechanisms.

Characterizing exposure to benzene, toluene, and naphthalene in firefighters wearing different types of new or laundered PPE.

The fire service has become more aware of the potential for adverse health outcomes due to occupational exposure to hazardous combustion byproducts. Because of these concerns, personal protective equipment (PPE) manufacturers have developed new protection concepts like particulate-blocking hoods to reduce firefighters' exposures. Additionally, fire departments have implemented exposure reduction interventions like routine laundering of PPE after fire responses. This study utilized a fireground exposure simulator (FES) with 24 firefighters performing firefighting activities on three consecutive days wearing one of three PPE ensembles (stratified by hood design and treatment of PPE): 1) new knit hood, new turnout jacket and new turnout pants 2) new particulate-blocking hood, new turnout jacket and new turnout pants or 3) laundered particulate-blocking hood, laundered turnout jacket and laundered turnout pants. As firefighters performed the firefighting activities, personal air sampling on the outside and inside the turnout jacket was conducted to quantify exposures to volatile organic compounds (VOCs) and naphthalene. Pre- and immediately post-fire exhaled breath samples were collected to characterize the absorption of VOCs. Benzene, toluene, and naphthalene were found to diffuse through and/or around the turnout jacket, as inside jacket benzene concentrations were often near levels reported outside the turnout jacket (9.7-11.7% median benzene reduction from outside the jacket to inside the jacket). The PPE ensemble did not appear to affect the level of contamination found inside the jacket for the compounds evaluated here. Benzene concentrations in exhaled breath increased significantly from pre to post-fire for all three groups (p-values < 0.05). The difference of pre-to post-fire benzene exhaled breath concentrations were positively associated with inside jacket and outside jacket benzene concentrations, even though self-contained breathing apparatus (SCBA) were worn during each response. This suggests the firefighters can absorb these compounds via the dermal route.

Characterizing exposures to flame retardants, dioxins, and furans among firefighters responding to controlled residential fires.

Firefighters may encounter items containing flame retardants (FRs), including organophosphate flame retardants (OPFRs) and polybrominated diphenyl ethers (PBDEs), during structure fires. This study utilized biological monitoring to characterize FR exposures in 36 firefighters assigned to interior, exterior, and overhaul job assignments, before and after responding to controlled residential fire scenarios. Firefighters provided four urine samples (pre-fire and 3-h, 6-h, and 12-h post-fire) and two serum samples (pre-fire and approximately 23-h post-fire). Urine samples were analyzed for OPFR metabolites, while serum samples were analyzed for PBDEs, brominated and chlorinated furans, and chlorinated dioxins. Urinary concentrations of diphenyl phosphate (DPhP), a metabolite of triphenyl phosphate (TPhP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), a metabolite of tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and bis(2-chloroethyl) phosphate (BCEtP), a metabolite of tris(2-chloroethyl) phosphate (TCEP), increased from pre-fire to 3-hr and 6-hr post-fire collection, but only the DPhP increase was statistically significant at a 0.05 level. The 3-hr and 6-hr post-fire concentrations of DPhP and BDCPP, as well as the pre-fire concentration of BDCPP, were statistically significantly higher than general population levels. BDCPP pre-fire concentrations were statistically significantly higher in firefighters who previously participated in a scenario (within the past 12 days) than those who were responding to their first scenario as part of the study. Similarly, firefighters previously assigned to interior job assignments had higher pre-fire concentrations of BDCPP than those previously assigned to exterior job assignments. Pre-fire serum concentrations of 2,3,4,7,8-pentachlorodibenzofuran (23478-PeCDF), a known human carcinogen, were also statistically significantly above the general population levels. Of the PBDEs quantified, only decabromodiphenyl ether (BDE-209) pre- and post-fire serum concentrations were statistically significantly higher than the general population. These results suggest firefighters absorbed certain FRs while responding to fire scenarios.

Survival by histology among patients with bone and soft tissue sarcoma who undergo metastasectomy: protocol for a systematic review and meta-analysis.

BACKGROUND: Metastasectomy is performed on a select cohort of patients with advanced and/or recurrent bone and soft tissue sarcomas because of the potential for long term relapse free and overall survival associated with the procedure. However, the evidence supporting metastasectomy is difficult to summarize without a systematic examination of existing literature. The objective of this systematic review will be to examine survival among both adults and children with advanced and recurrent bone and STS who undergo metastasectomy. METHODS: We designed and registered a study protocol for a systematic review and meta-analysis. We will include data from survival studies (e.g., randomized trials, cohort studies, routine case registries, and case control) conducted in children and adults with advanced and recurrent bone and soft tissue sarcoma who undergo metastasectomy. The primary outcome will be overall survival. Secondary outcomes will be 30-day post-operative mortality, recurrence-free survival, time off systemic therapy, and patient-reported outcomes including quality of life end points where available. Literature searches will be performed in multiple electronic databases including Ovid MEDLINE ® (1946 to present), Ovid EMBASE (1974 to present), Web of Science, and Cochrane Library. Grey literature will be identified through searching references, conference abstracts, Papers First, and Google Scholar. Two investigators will independently screen all citations, full-text articles, and abstract data. Full-text articles selected for analysis will be assessed for quality and risk of bias. If feasible, we will conduct a random effects meta-analysis. Estimates will be stratified according to histology comparing survival based on organ of metastasectomy. Additional analysis will be conducted to explore the potential sources of heterogeneity according to various patient, disease, and treatment characteristics (e.g., metastasis status, age, disease burden, and concomitant interventions). DISCUSSION: This systematic review and meta-analysis will identify, evaluate, and integrate data on survival of metastasectomy of bone and soft tissue sarcoma by organ of metastasis. Our findings may have implications for clinicians, patients, and their families when considering selection for resection of oligometastatic disease in de novo, or recurrent bone and soft tissue sarcoma. Implications for future research will be identified to improve the outcomes of these complex patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019126906.

TEAD-YAP Interaction Inhibitors and MDM2 Binders from DNA-Encoded Indole-Focused Ugi Peptidomimetics.

DNA-encoded combinatorial synthesis provides efficient and dense coverage of chemical space around privileged molecular structures. The indole side chain of tryptophan plays a prominent role in key, or "hot spot", regions of protein-protein interactions. A DNA-encoded combinatorial peptoid library was designed based on the Ugi four-component reaction by employing tryptophan-mimetic indole side chains to probe the surface of target proteins. Several peptoids were synthesized on a chemically stable hexathymidine adapter oligonucleotide "hexT", encoded by DNA sequences, and substituted by azide-alkyne cycloaddition to yield a library of 8112 molecules. Selection experiments for the tumor-relevant proteins MDM2 and TEAD4 yielded MDM2 binders and a novel class of TEAD-YAP interaction inhibitors that perturbed the expression of a gene under the control of these Hippo pathway effectors.

Management of Firefighters' Chemical & Cardiovascular Exposure Risks on the Fireground.

The fire service research community around the world has focused substantial resources on reducing firefighter risk for sudden cardiac events and chemical exposures that may lead to cancer. Research presented here summarizes important lessons learned from a full-scale residential Fire Study that allowed quantification of the risks as well as the effectiveness of interventions to reduce those risks. To address fireground exposure concerns, personal protective equipment (PPE) and administrative controls exist. But, these controls are not always straightforward to apply. Leadership and management concerns with ongoing implementation of these controls are introduced and opportunities for change management are discussed. While research provides a solid basis upon which to institute policy and practice, fireground leadership and management is critical to ensure appropriate implementation.

Firefighters' and instructors' absorption of PAHs and benzene during training exercises.

INTRODUCTION: Training fires may constitute a major portion of some firefighters' occupational exposures to smoke. However, the magnitude and composition of those exposures are not well understood and may vary by the type of training scenario and fuels. OBJECTIVES: To understand how structure fire training contributes to firefighters' and instructors' select chemical exposures, we conducted biological monitoring during exercises involving combustion of pallet and straw and oriented strand board (OSB) or the use of simulated smoke. METHODS: Urine was analyzed for metabolites of polycyclic aromatic hydrocarbons (PAHs) and breath was analyzed for volatile organic compounds (VOCs) including benzene. RESULTS: Median concentrations of nearly all PAH metabolites in urine increased from pre-to 3-hr post-training for each scenario and were highest for OSB, followed by pallet and straw, and then simulated smoke. For instructors who supervised three trainings per day, median concentrations increased at each collection. A single day of OSB exercises led to a 30-fold increase in 1-hydroxypyrene for instructors, culminating in a median end-of-shift concentration 3.5-fold greater than median levels measured from firefighters in a previous controlled-residential fire study. Breath concentrations of benzene increased 2 to 7-fold immediately after the training exercises (with the exception of simulated smoke training). Exposures were highest for the OSB scenario and instructors accumulated PAHs with repeated daily exercises. CONCLUSIONS: Dermal absorption likely contributed to the biological levels as the respiratory route was well protected. Training academies should consider exposure risks as well as instructional objectives when selecting training exercises.

Immunotherapy with check-point inhibitors (CPI) in adult malignancies: a protocol for the systematic review of the quality of economic analyses.

BACKGROUND: Immuno-oncology, and in particular, check-point inhibitors (CPIs), have led to a paradigm shift in the field of cancer care. The cost of new drug development is high, and many novel agents in oncology are significantly more expensive than older agents. Therefore, healthcare funders have factored measures of cost-effectiveness into decisions concerning drug reimbursement and incorporation of new agents into treatment algorithms. The methodology of cost-effectiveness evaluations, however, is less rigorously applied than those evaluating clinical efficacy and safety data. Thus, in spite of many regulatory bodies having approved CPIs based on existing economic analyses, to date, there has not been a systematic evaluation of the quality of health economic studies conducted on this new class of agents. Therefore, we propose to systematically review the methodologic and reporting quality of cost-effectiveness and cost-utility studies assessing CPIs to alternate established therapies, other immuno-oncology regimens, or placebo, in adults with malignancies. METHODS/DESIGN: The systematic review will include all published economic evaluations of CPIs compared with at least one other treatment in adult patients with solid or hematologic malignancies. A search will be performed to identify relevant studies in Ovid MEDLINE, EMBASE, Cost-effectiveness Analysis Registry, Evidence-Based Medicine Reviews, and the NIHR-HTA database. The titles and abstracts of all identified studies will be independently reviewed by two reviewers, who will then assess the full text of all articles deemed to meet eligibility criteria. Assessed articles will be screened for compliance with the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) criteria. The association, with CHEERS criteria, of the journal impact factor, publication year, funding source, tumor site, trial or model-based study, and CPIs studied, will then be assessed. DISCUSSION: The systematic review will aim to provide an overview of the quality of economic analyses evaluating CPIs for the treatment of malignancies in adult patients. Any systemic or recurrent deficiencies in methodological or reporting quality will be described and used to inform recommendations for improved reporting of economic analyses. SYSTEMATIC REVIEW REGISTRATION: This review will not be registered with PROSPERO, it does not meet the eligibility criterion of addressing an outcome of the direct patient or clinical relevance.