Impact of smoking status on clinical outcomes in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based regimens.

BACKGROUND: Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens. MATERIALS AND METHODS: Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively. Patients with mRCC who received either dual ICI therapy or ICI with VEGF-TKI in the first-line setting were included and were categorized as current, former, or nonsmokers. The primary outcomes were OS, time to treatment failure (TTF), and objective response rate (ORR). OS and TTF were compared between groups using the log-rank test and multivariable Cox regression models. ORR was assessed between the 3 groups using a multivariable logistic regression model. RESULTS: A total of 989 eligible patients were included in the analysis, with 438 (44.3%) nonsmokers, 415 (42%) former, and 136 (13.7%) current smokers. Former smokers were older and included more males, while other baseline characteristics were comparable between groups. Median follow-up for OS was 21.2 months. In the univariate analysis, a significant difference between groups was observed for OS (P = .027) but not for TTF (P = .9), with current smokers having the worse 2-year OS rate (62.8% vs 70.8% and 73.1% in never and former smokers, respectively). After adjusting for potential confounders, no significant differences in OS or TTF were observed among the 3 groups. However, former smokers demonstrated a higher ORR compared to never smokers (OR 1.45, P = .02). CONCLUSION: Smoking status does not appear to independently influence the clinical outcomes to first-line ICI-based regimens in patients with mRCC. Nonetheless, patient counseling on tobacco cessation remains a crucial aspect of managing patients with mRCC, as it significantly reduces all-cause mortality.

Characterization of Patients with Metastatic Renal Cell Carcinoma Undergoing Deferred, Upfront, or No Cytoreductive Nephrectomy in the Era of Combination Immunotherapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: The role of cytoreductive nephrectomy (CN) has not yet been well characterized in the era of combination immunotherapy. OBJECTIVE: To evaluate characteristics and outcomes for patients with metastatic renal cell carcinoma (mRCC) who received immuno-oncology (IO)-based combination therapy according to CN status. DESIGN, SETTING, AND PARTICIPANTS: Using the International mRCC Database Consortium (IMDC), patients with mRCC who received frontline IO-based combinations were included. Upfront CN was defined as CN up to 3 mo before diagnosis of metastatic disease but before systemic therapy initiation. Deferred CN was defined as CN after systemic therapy initiation. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) from initiation of systemic therapy was estimated via Cox proportional-hazards regression. A 12-mo landmark time and a time-varying covariate for CN status were used to mitigate potential bias. RESULTS AND LIMITATIONS: Of the 385 patients eligible for landmark analysis, 24, 182, and 179 underwent deferred CN, upfront CN, and no CN, respectively. Patients in the no CN subgroup were older (63 yr vs 57 yr in the deferred CN subgroup and 60 yr in the upfront CN subgroup; p = 0.001) and a higher proportion had bone metastases (44% vs 26% in the deferred CN subgroup and 23% in the upfront CN subgroup; p < 0.001). A lower proportion of patients in the upfront CN subgroup had IMDC poor risk (23% vs 43% in the no CN subgroup and 47% in the deferred CN subgroup; p < 0.001). On multivariable analysis, CN receipt was an independent favorable prognostic factor (hazard ratio 0.45, 95% confidence interval 0.26-0.78; p = 0.005). The study is limited by the lack of randomization and its retrospective nature. CONCLUSIONS: Despite changes in practice patterns with the advent of novel therapeutic agents, CN may still serve as an effective surgical intervention in carefully selected patients. PATIENT SUMMARY: For patients with metastatic kidney cancer, surgery to remove the primary tumor was traditionally the treatment of choice, but immunotherapy drugs are now another option for these patients. We analyzed data for contemporary patients with metastatic kidney cancer who received combination immunotherapy as their first treatment. We found that in selected patients receiving immunotherapy, surgery to remove the primary tumor as well can result in better prognosis.

High-dose chemotherapy with autologous stem-cell transplantation for relapsed metastatic germ cell tumors: The Alberta experience.

INTRODUCTION: High-dose chemotherapy with autologous stem-cell transplantation (HDCASCT) is standard therapy for metastatic germ cell tumors (mGCTs) in patients whose disease progresses during or after conventional chemotherapy. We conducted a retrospective review of HDC-ASCT in relapsed mGCT patients in the province of Alberta, Canada over the past two decades. METHODS: Patients with mGCTs who received HDC-ASCT at two provincial cancer referral centers from 2000-2018 were identified from institutional databases. Baseline clinical and treatment characteristics were collected, as well as overall survival (OS) and disease-free survival (DFS). Relevant prognostic variables were analyzed. RESULTS: Forty-three patients were identified. The median age was 28 years (range 19-56). A majority (95%) had non-seminoma histology and testis/retroperitoneal primary (84%). Twenty patients (47%) had poor-risk disease, as per The International Germ Cell Consensus Classification (IGCCC), at start of first-line chemotherapy. HDC-ASCT was used as second-line therapy in 65% of patients, and 58% of ASCT patients received tandem transplants. Median followup after ASCT was 22 months (range 2-181). At last followup, 42% of patients were alive without disease, including 3/7 (43%) of patients with primary mediastinal disease. Two-year and five-year DFS/OS ratios were 44%/65% and 38%/45%, respectively. Median OS and DFS for all patients were 30.0 months (13.3-46.6) and 8.0 months (0.9-15.1), respectively. CONCLUSIONS: We found that HDC-ASCT is an effective salvage therapy in mGCT, consistent with existing literature. Patients appeared to benefit regardless of primary site. Though limited by small sample size, we found a numerical difference in DFS and OS between second- and third-line HDC-ASCT and single vs. tandem ASCT.

An embedded cluster CASPT2 study of the Ce:YVO4 spectrum.

Multiconfigurational theory, in combination with the embedded cluster approach, is a precise and ab initio approach to describe the electronic structure of solids. In this work, the spectrum of a Ce(III) dopant in YVO4 has been studied by complete active space perturbation theory of the second order (CASPT2), with the host material represented as a set of ab initio model potentials and point-charges. We assess the sensitivity of the spectrum to the size of both the embedded cluster size as well as the size of the electronic basis set. A comparison of our best computational model with experimental results shows that the embedding approach is robust and can accurately model the spectrum of low-concentration dopants in complex host materials.

Assessment of DFT functionals for a minimal nitrogenase [Fe(SH)4H]- model employing state-of-the-art ab initio methods.

We have designed a [Fe(SH)4H]- model with the fifth proton binding either to Fe or S. We show that the energy difference between these two isomers (∆E) is hard to estimate with quantum-mechanical (QM) methods. For example, different density functional theory (DFT) methods give ∆E estimates that vary by almost 140 kJ/mol, mainly depending on the amount of exact Hartree-Fock included (0%-54%). The model is so small that it can be treated by many high-level QM methods, including coupled-cluster (CC) and multiconfigurational perturbation theory approaches. With extrapolated CC series (up to fully connected coupled-cluster calculations with singles, doubles, and triples) and semistochastic heat-bath configuration interaction methods, we obtain results that seem to be converged to full configuration interaction results within 5 kJ/mol. Our best result for ∆E is 101 kJ/mol. With this reference, we show that M06 and B3LYP-D3 give the best results among 35 DFT methods tested for this system. Brueckner doubles coupled cluster with perturbaitve triples seems to be the most accurate coupled-cluster approach with approximate triples. CCSD(T) with Kohn-Sham orbitals gives results within 4-11 kJ/mol of the extrapolated CC results, depending on the DFT method. Single-reference CC calculations seem to be reasonably accurate (giving an error of ∼5 kJ/mol compared to multireference methods), even if the D1 diagnostic is quite high (0.25) for one of the two isomers.

Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma.

BACKGROUND: The combination of immuno-oncology (IO) agents ipilimumab and nivolumab (IPI-NIVO) and vascular endothelial growth factor targeted therapies (VEGF-TT) combined with IO (IO-VEGF) are current standard of care first-line treatments for metastatic renal cell carcinoma (mRCC). OBJECTIVE: To establish real-world clinical benchmarks for IO combination therapies based on the International mRCC Database Consortium (IMDC) criteria. DESIGN, SETTING, AND PARTICIPANTS: Patients with mRCC who received first-line IPI-NIVO, IO-VEGF, or VEGF-TT from 2002 to 2021 were identified using the IMDC database and stratified according to IMDC risk groups. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), time to next treatment (TTNT), and treatment duration (TD) were calculated using the Kaplan-Meier method and compared between IMDC risk groups within each treatment cohort by the log-rank test. The overall response rate (ORR) was calculated by physician assessment of the best overall response. The primary outcome was OS at 18 mo. RESULTS AND LIMITATIONS: In total, 728 patients received IPI-NIVO, 282 IO-VEGF, and 7163 VEGF-TT. The median follow-up times for patients remaining alive were 14.3 mo for IPI-NIVO, 14.9 mo IO-VEGF, and 34.4 mo for VEGF-TT. OS at 18 mo for favorable, intermediate, and poor risk was, respectively, 90%, 78%, and 50% for those receiving IPI-NIVO; 93%, 83%, and 74% for IO-VEGF; and 84%, 64%, and 28% for VEGF-TT. ORRs in favorable-, intermediate-, and poor-risk groups were 41.3%, 40.6%, and 33.0% for those receiving IPI-NIVO; 60.3%, 56.8%, and 40.9% for IO-VEGF; and 39.3%, 33.5%, and 20.9% for VEGF-TT, respectively. The IMDC model stratified patients into statistically distinct risk groups for the three endpoints of OS, TTNT, and TD within each treatment cohort. Limitations of this study were the retrospective design and short follow-up. CONCLUSIONS: This study demonstrated that the IMDC model continues to risk stratify patients with mRCC treated with contemporary first-line IO combination therapies and provided real-world survival benchmarks. PATIENT SUMMARY: The International Metastatic Renal Cell Carcinoma Database Consortium model continues to stratify patients with metastatic renal cell carcinoma receiving modern combination treatments in the real-world setting.

In silico evidence for the utility of parsimonious root phenotypes for improved vegetative growth and carbon sequestration under drought.

Drought is a primary constraint to crop yields and climate change is expected to increase the frequency and severity of drought stress in the future. It has been hypothesized that crops can be made more resistant to drought and better able to sequester atmospheric carbon in the soil by selecting appropriate root phenotypes. We introduce OpenSimRoot_v2, an upgraded version of the functional-structural plant/soil model OpenSimRoot, and use it to test the utility of a maize root phenotype with fewer and steeper axial roots, reduced lateral root branching density, and more aerenchyma formation (i.e. the 'Steep, Cheap, and Deep' (SCD) ideotype) and different combinations of underlying SCD root phene states under rainfed and drought conditions in three distinct maize growing pedoclimatic environments in the USA, Nigeria, and Mexico. In all environments where plants are subjected to drought stress the SCD ideotype as well as several intermediate phenotypes lead to greater shoot biomass after 42 days. As an additional advantage, the amount of carbon deposited below 50 cm in the soil is twice as great for the SCD phenotype as for the reference phenotype in 5 out of 6 simulated environments. We conclude that crop growth and deep soil carbon deposition can be improved by breeding maize plants with fewer axial roots, reduced lateral root branching density, and more aerenchyma formation.

Modeling root loss reveals impacts on nutrient uptake and crop development.

Despite the widespread prevalence of root loss in plants, its effects on crop productivity are not fully understood. While root loss reduces the capacity of plants to take up water and nutrients from the soil, it may provide benefits by decreasing the resources required to maintain the root system. Here, we simulated a range of root phenotypes in different soils and root loss scenarios for barley (Hordeum vulgare), common bean (Phaseolus vulgaris), and maize (Zea mays) using and extending the open-source, functional-structural root/soil simulation model OpenSimRoot. The model enabled us to quantify the impact of root loss on shoot dry weight in these scenarios and identify in which scenarios root loss is beneficial, detrimental, or has no effect. The simulations showed that root loss is detrimental for phosphorus uptake in all tested scenarios, whereas nitrogen uptake was relatively insensitive to root loss unless main root axes were lost. Loss of axial roots reduced shoot dry weight for all phenotypes in all species and soils, whereas lateral root loss had a smaller impact. In barley and maize plants with high lateral branching density that were not phosphorus-stressed, loss of lateral roots increased shoot dry weight. The fact that shoot dry weight increased due to root loss in these scenarios indicates that plants overproduce roots for some environments, such as those found in high-input agriculture. We conclude that a better understanding of the effects of root loss on plant development is an essential part of optimizing root system phenotypes for maximizing yield.

Convergence of Electronic Structure Properties in Ionic Oxides Within a Fragment Approach.

Embedded-cluster models of crystalline solids are important to allow accurate wave function methods to be applicable to solids. The ab-initio model potential method, in which the crystal is divided into three different fragments, one quantum fragment, one ab-initio model potential fragment and one point-charge fragment, has historically been shown to be a viable tool for describing the electronic structure in ionic solids. The optimal size of these regions is, of course, individual for each crystal. In this study we analyzed the convergence of the electronic structure properties with respect to an increase of the size of the quantum part and the layer of potentials. MgO crystal and Ni: MgO were used for this purpose as examples of an ideal crystal and a crystal with a point defect. We demonstrated that with an increase of the cluster size, the electron density in the inner part of the cluster becomes very similar to the electron density in the periodic model. Clusters, embedded into a layer of model potential and electrostatic field, are a good alternative to periodic description.

Imaging Response to Contemporary Immuno-oncology Combination Therapies in Patients With Metastatic Renal Cell Carcinoma.

Importance: The association between treatment with first-line immuno-oncology (IO) combination therapies and physician-assessed objective imaging response among patients with metastatic renal cell carcinoma (mRCC) remains uncharacterized. Objective: To compare the likelihood of objective imaging response (ie, complete or partial response) to first-line IO combination ipilimumab-nivolumab (IOIO) therapy vs approved IO with vascular endothelial growth factor inhibitor (IOVE) combination therapies among patients with mRCC. Design, Setting, and Participants: This multicenter international cohort study was nested in routine clinical practice. A data set from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) was used to identify consecutive patients with mRCC who received treatment with IO combination therapies between May 30, 2013, and September 9, 2021. A total of 899 patients with a histologically confirmed diagnosis of mRCC who received treatment with a first-line IOVE or IOIO regimen and had evaluable responses were included. Exposures: Best overall response to first-line IO combination therapy based on Response Evaluation Criteria in Solid Tumors, version 1.1. Main Outcomes and Measures: The primary outcome was the difference in treating physician-assessed objective imaging response based on the type of first-line IO combination therapy received. Secondary outcomes included the identification of baseline characteristics positively associated with objective imaging response and the association of objective imaging response with overall survival. Results: Among 1085 patients with mRCC who received first-line IO combination therapies, 899 patients (median age, 62.8 years [IQR, 55.9-69.2 years]; 666 male [74.2%]) had evaluable responses. A total of 794 patients had information available on IMDC risk classification; of those, 127 patients (16.0%) had favorable risk, 442 (55.7%) had intermediate risk, and 225 (28.3%) had poor risk. With regard to best overall response among all participants, 37 patients (4.1%) had complete response, 344 (38.3%) had partial response, 315 (35.0%) had stable disease, and 203 (22.6%) had progressive disease. Corresponding median overall survival was not estimable (95% CI, 53.3 months to not estimable) among patients with complete response, 55.9 months (95% CI, 44.1 months to not estimable) among patients with partial response, 48.1 months (95% CI, 33.4 months to not estimable) among patients with stable disease, and 13.0 months (95% CI, 8.4-18.1 months) among patients with progressive disease (log rank P < .001). Treatment with IOVE therapy was found to be independently associated with an increased likelihood of obtaining response (OR, 1.89; 95% CI, 1.26-2.81; P = .002) compared with IOIO therapy. The presence of lung metastases (odds ratio [OR], 1.49; 95% CI, 1.01-2.20), receipt of cytoreductive nephrectomy (OR, 1.59; 95% CI, 1.04-2.43), and favorable IMDC risk (OR, 1.93; 95% CI, 1.10-3.39) were independently associated with an increased likelihood of response. Conclusions and Relevance: In this study, treatment with IOVE therapy was associated with significantly increased odds of objective imaging response compared with IOIO therapy. The presence of lung metastases, receipt of cytoreductive nephrectomy, and favorable IMDC risk were associated with increased odds of experiencing objective imaging response. These findings may help inform treatment selection, especially in clinical contexts associated with high-volume multisite metastatic disease, in which obtaining objective imaging response is important.

Simulating Crop Root Systems Using OpenSimRoot.

Functional-structural plant models are valuable modeling tools in analyzing plant development. A functional-structural plant model combines a three-dimensional representation of plant structure with models for physiological functions in order to better understand plant development. We present a guide to simulating crop root systems with OpenSimRoot, a feature-rich, highly cited, and open-source functional-structural root architecture model. We describe in detail how to create your own input files in conjunction with some examples. The aim of this guide is to highlight the potential of computational modeling in biology and to make modeling more accessible to the plant science community.

Theoretical evidence that root penetration ability interacts with soil compaction regimes to affect nitrate capture.

BACKGROUND AND AIMS: Although root penetration of strong soils has been intensively studied at the scale of individual root axes, interactions between soil physical properties and soil foraging by whole plants are less clear. Here we investigate how variation in the penetration ability of distinct root classes and bulk density profiles common to real-world soils interact to affect soil foraging strategies. METHODS: We utilize the functional-structural plant model 'OpenSimRoot' to simulate the growth of maize (Zea mays) root systems with variable penetration ability of axial and lateral roots in soils with (1) uniform bulk density, (2) plow pans and (3) increasing bulk density with depth. We also modify the availability and leaching of nitrate to uncover reciprocal interactions between these factors and the capture of mobile resources. KEY RESULTS: Soils with plow pans and bulk density gradients affected overall size, distribution and carbon costs of the root system. Soils with high bulk density at depth impeded rooting depth and reduced leaching of nitrate, thereby improving the coincidence of nitrogen and root length. While increasing penetration ability of either axial or lateral root classes produced root systems of comparable net length, improved penetration of axial roots increased allocation of root length in deeper soil, thereby amplifying N acquisition and shoot biomass. Although enhanced penetration ability of both root classes was associated with greater root system carbon costs, the benefit to plant fitness from improved soil exploration and resource capture offset these. CONCLUSIONS: While lateral roots comprise the bulk of root length, axial roots function as a scaffold determining the distribution of these laterals. In soils with high soil strength and leaching, root systems with enhanced penetration ability of axial roots have greater distribution of root length at depth, thereby improving capture of mobile resources.

Oxygen chemistry of halogen-doped CeO2(111).

We study substitutional fluorine, chlorine and bromine impurities at CeO2(111), and their effects on the oxygen chemistry of the surface, using density functional theory. We find that impurity formation results in a halide ion and one Ce3+ ion for all three halogens, although the formation energy depends strongly on the identity of the halogen; however, once formed, all three halogens exhibit a similar propensity to form impurity-impurity pairs. Furthermore, while the effects of halogen impurities on oxygen vacancy formation are marginal, they are more significant for oxygen molecule adsorption, due to electron transfer from the Ce3+ ion which results in an adsorbed superoxide molecule. We also consider the displacement of a halide ion on to the surface by half of an oxygen molecule, and find that the energy required to do so depends strongly not only on the identity of the halogen, but also on whether or not a second halogen impurity, with its associated Ce3+ ion, is present; if it is, then the process is greatly facilitated. Overall, our results demonstrate the existence of a rich variety of ways in which the oxygen chemistry of CeO2(111) may be modified by the presence of halogen dopants.

Efficacy of immune-checkpoint inhibitors (ICI) in the treatment of older adults with metastatic renal cell carcinoma (mRCC) - an International mRCC Database Consortium (IMDC) analysis.

OBJECTIVE: Older adults with metastatic renal cell carcinoma(mRCC) are underrepresented in immune-checkpoint inhibitor(ICI) registration trials. Here we compare the efficacy of ICI treatments in older vs. younger adults with mRCC. METHODS: Using the International mRCC Database Consortium(IMDC), patients treated with a PD(L)-1 based ICI were identified. Older adult was defined as ≥70-years at the time of treatment. Descriptive statistics were summarized in means, medians, and proportions. Effectiveness endpoints included overall survival (OS), time-to-treatment failure(TTF), time-to-next treatment(TNT), and overall response rate(ORR). Hazards ratios were adjusted(aHR) for IMDC risk factors, histology, line of treatment and older age. RESULTS: Of 1427 included patients, 397(28%) were older adults. ICI was used as 1st line(1 L) in 40%, 2nd line(2 L) in 49% and 3rd line(3 L) in 11% of patients. In univariable analysis, older adults had inferior OS compared to younger adults(25.1 m vs. 30.8 m, p < 0.01). There were no significant differences in TTF (6.9 m vs. 6.9 m, p = 0.4) or TNT(9.1 m vs 10 m, p = 0.3) between groups. In multivariable analyses, older age was not independently associated with worse OS(aHR = 1.02, p = 0.8), TTF(aHR = 0.95, p = 0.6) or TNT(aHR = 0.93, p = 0.5). Older adults had a lower ORR compared to younger adults(24% vs. 31%, p = 0.01), which was mainly driven by responses in 1 L(31% vs. 44%, p = 0.02) and not observed in 2 L/3 L. CONCLUSIONS: After multivariable analyses, older adults with mRCC treated with ICI had no difference in OS, TTF or TNT when compared to younger adults. Our data support that chronological older age should not preclude patients from receiving ICI based therapies.

Teachers With Special Needs. De-Psychiatrization of Children in Schools.

Psychiatrization not only affects adults. Ever more children in Western countries are being diagnosed with a mental disorder of behavior, such as ADHD. Children may often be labelled with the best intentions, for example in order to be able to provide them with suitable care and guidance. However, this labelling can have exclusionary effects and often entails the consequence that important discussion about contextual factors that give rise to (the perception of) unwelcome behavior or academic underperformance rarely, if at all, takes place. In this article we contend that although children are of central concern to schools and the design of pupils' education, it is important not to make pupils the sole owner of problems that arise. It is therefore high time that a far more critical normative stance towards inclusive education is taken, in which the presently widespread biomedical approach is met with a school community response that focuses not on the nature of individual disorders but on the special need for additional capacity that schools and teachers have in meeting (perceived) deviant behaviors and emotions and/or academic underperformance. We argue that teaching should not set out to remedy individual diagnoses, but that teachers should be supported to extend their professional competence to the benefit of all pupils.

Corrigendum: Teachers with Special Needs. De-Psychiatrization of Children in Schools.

[This corrects the article DOI: 10.3389/fsoc.2021.781057.].

[Association of physical activity with fatigue and functional capacity in patients with rheumatoid arthritis]. / Zusammenhang von körperlicher Aktivität mit Fatigue und Funktionskapazität bei Patienten mit rheumatoider Arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) tend to be less physically active. Physical activity has been shown to have a positive impact on disease activity and quality of life and is recommended by the European League Against Rheumatism (EULAR) as an integral component of standard treatment. OBJECTIVE: A cross-sectional analysis of RA patients was carried out assessing disease activity, functional capacity and fatigue associated with physical activity. MATERIAL AND METHODS: Physical activity, functional capacity and the global fatigue index (GFI) were examined using standardized questionnaires: the international physical activity questionnaire short form (IPAQ-SF), the functional questionnaire Hannover (FFbH) and the multidimensional assessment of fatigue (MAF). The data were evaluated using SPSS 26 (IBM, Armonk, NY, USA). The level of significance was tested with bivariate and partial correlations and nonparametric tests. RESULTS: In total 164 patients were included in the study. The majority of the patients were female (127/164; 77%) and the median age of the cohort was 58.3 years (range 21-86 years). The median duration of disease-related symptoms at inclusion was 169 months (range 0-713 months). Physical activity was low in 39%, moderate in 37% and high in 24%. Patients reporting higher levels of physical activity reported significantly lower GFI (p < 0.001), functional limitations (p < 0.001) and disease activity (p = 0.045) scores than those with less physical activity. CONCLUSION: Physical activity in RA patients was significantly correlated with functional capacity and levels of fatigue. In order to reduce the proportion of patients with low physical activity, the possibilities for functional training should be expanded and the patients should be encouraged to undertake sporting activities.

Multidisciplinary management of locally advanced and metastatic cutaneous squamous cell carcinoma.

Non-melanoma skin cancers are the most prevalent form of cancer, with cutaneous squamous cell carcinoma (cscc) being the 2nd most common type. Patients presenting with high-risk lesions associated with locally advanced or metastatic cscc face high rates of recurrence and mortality. Accurate staging and risk stratification for patients can be challenging because no system is universally accepted, and no Canadian guidelines currently exist. Patients with advanced cscc are often deemed ineligible for either or both of curative surgery and radiation therapy (rt) and, until recently, were limited to off-label systemic cisplatin-fluorouracil or cetuximab therapy, which offers modest clinical benefits and potentially severe toxicity. A new systemic therapy, cemiplimab, has been approved for the treatment of locally advanced and metastatic cscc. In the present review, we provide recommendations for patient classification and staging based on current guidelines, direction for determining patient eligibility for surgery and rt, and an overview of the available systemic treatment options for advanced cscc and of the benefits of a multidisciplinary approach to patient management.