Screening biorefinery pathways to biodiesel, green-diesel and propylene-glycol: A hierarchical sustainability assessment of process.

Plant design implies the best choice among a set of feedstock-to-product process pathways. Multiple sustainability performance indicators can blur the decision, and existing sustainability assessment methods usually focus only on environmental life-cycle performance and corporate metrics or solely on the gate-to-gate process. It is relevant to incorporate integrated system analysis to address sustainability comprehensively. To this end, the Sustainable Process Systems Engineering (S-PSE) method was previously introduced to select the most sustainable feedstock-process-product configuration via four-dimensional indicators (environment, efficiency, health-&-safety, and economic), and then pinpoint the sustainability hotspots of the best design to unveil possible improvements. This work expands S-PSE by adding new features: (i) cradle-to-gate environmental assessment; (ii) composition of flowsheets; (iii) new indicators; (iv) statistical screening of indicators; and (v) 2030 Agenda compliance. A biorefinery case-study demonstrates S-PSE: to select the best pathway from soybean-oil, palm-oil, and microalgae-oil to biodiesel, green-diesel, and propylene-glycol. Firstly, statistical screening reduces the indicator set by 62%. Results evince all routes from microalgae-oil as economically unfeasible due to oil cost, despite superior environmental performance. S-PSE evinces palm-oil-to-biodiesel as the most sustainable due to lower cradle-to-gate emissions and manufacturing cost, with sustainability hotspots associated to hazardous methanol input and energy-intensive distillations. 2030 Agenda analysis also outlines palm-oil-to-biodiesel as best for 5 out of 10 Sustainable Development Goals linked to the reduced indicator set.

Ultrasonography Reliability in the Detection of Inflammatory and Structural Abnormalities: An Exercise in Multiple Joints.

BACKGROUND: Ultrasonography is an image technique that allows rheumatologists to visualize structural and inflammatory changes within a joint. The objective of this study was to assess the interobserver and intraobserver reliability of musculoskeletal ultrasound (US) in the detection of inflammatory and destructive joint changes in patients with polyarthritis. METHODS: A Delphi exercise was undertaken to standardize and adapt the EULAR-OMERACT elementary US definitions of inflammatory lesions (effusion, synovial hypertrophy, power Doppler, bone erosions, and synovitis) for each joint. Fifteen patients were analyzed, and video clips of 600 joints were collected. Each joint was scored for the presence of each elementary component, on 2 separate occasions, by 6 examiners. Interobserver and intraobserver agreement analysis was assessed through Fleiss κ coefficient (κ). RESULTS: Considering all patients and all joints, the interobserver values were highest for erosions and lowest for effusion (κ = 0.7314 and κ = 0.6044, respectively). When analyzing different regions, the highest interobserver agreement was for tibiotalar joint (κ = 0.8043) and the lowest for wrist (κ = 0.6767). Intraobserver reliability was excellent for each and all elementary components and anatomical region. CONCLUSIONS: The present study showed either a good or excellent US interobserver and intraobserver reliability in elementary elements and anatomical region. This kind of US reliability exercises are important for standardization of exploration in everyday practice by reducing the variability associated with this imaging technique, and ensuring a greater degree of homogeneity and future comparability in the assessment of disease activity in polyarthritis patients.

Septic Polyarthritis by Staphylococcus aureus of "Unknown Origin".

ABSTRACT: More than 90% of septic arthritis cases are monoarticular. Joint infection can occur through several mechanisms such as hematogenous dissemination, by contiguity from adjacent infected soft tissue, surgical contamination, direct inoculation, or joint trauma.We report the case of a 69-year-old man admitted to our hospital with septic polyarthritis. The presented case is remarkable given its atypical presentation. The patient had no known risk factors for septic arthritis, comorbidities, or history of recurrent infections that could suggest some degree of immunosuppression. The atypical polyarticular involvement at presentation, the absence of sustained fever, and the good general condition of the patient delayed the diagnosis and treatment.

Novel ethylene oxide production with improved sustainability: Loss prevention via supersonic separator and carbon capture.

Sustainability must be always assured in process design. Not rarely, multiple sustainability criteria point oppositely, entailing a need for more systematic and coherent assessments. The Sustainable Process Systems Engineering method is introduced as a two-level hierarchical evaluation of process designs. The first level selects the best design via four-dimensional indicators (environment, efficiency, health-&-safety, and economic), while in the second level, sustainability hotspots of the best design are pinpointed to unveil possible improvements. The method is applied for sustainability assessment of two ethylene oxide processes: the conventional and a novel route employing supersonic separator to prevent ethylene oxide losses using liquid-water injection. Supersonic separator route reduces oxide losses by 83.33 kg/h, representing +0.9% greater ethylene oxide production, 95% less ethylene oxide losses, entailing 2.5% higher net value for 20 operation years despite 0.11% higher investment, and consequently exhibiting the best environmental, technical, health-&-safety and economic performances. Photochemical-oxidation and aquatic-ecotoxicity are environmental indicators with highest improvement due to supersonic separator inclusion. Ethylene oxidation reactor, carbon dioxide stripping-column and cooling-water tower are the main unit-operations with sustainability hotspots.

Evaluation of the performance of extreme patient-reported outcomes as surrogate markers for fibromyalgia in axial spondyloarthritis.

OBJECTIVES: The aim of the study is to evaluate the performance of extreme patient-reported outcomes (PRO) against definitions of fibromyalgia (FM) in patients with axial spondyloarthritis (axSpA). METHODS: Ancillary analysis of the Predict-SpA trial, an observational study of axSpA patients receiving TNF-α inhibitor, was performed. 'Extreme PRO' was defined as a score ≥ 8 on three out of the first five Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions (scored 0-10). FM was defined by the American College of Rheumatology (ACR) 1990 criteria and the Fibromyalgia Rapid Screening Test (FiRST). Performances of 'extreme PRO' for FM were evaluated by the sensitivity, specificity and positive likelihood ratio using the 1990 ACR criteria as gold standard. As secondary analysis, the FiRST was used as the external standard. RESULTS: The prevalence of 'extreme PRO' in this population was 28.8% at baseline and decreased to 9.9% at 12 weeks. 'Extreme PRO' had low sensitivity 12 weeks after TNF initiation (0.18, 95% confidence interval [CI] 0.10-0.27 vs 0.60, 95% CI 0.50-0.71, at baseline), but high specificity (0.92, 95% CI 0.89-0.94 vs 0.78, 95% 0.74-0.82, at baseline), using ACR 1990 criteria as gold standard. Performances when tested against FiRST at 12 weeks showed higher sensitivity (0.27, 95% CI 0.20-0.35) and specificity (0.96, 95% CI 0.94-0.98). CONCLUSION: The proposed extreme PRO definition showed great specificity for FM recognition in patients with axSpA, suggesting it could be used in observational studies when specific items for FM classification are not available.

Bilateral transient osteoporosis of the hip: a neglected cause of hip pain during pregnancy.

Transient osteoporosis of the hip (TOH) is an important but often neglected cause of hip pain, which can gradually lead to debilitating mobility and carries risks such as fracture or avascular necrosis. A 39-year-old woman presented to the Rheumatology department two weeks post-cesarean delivery, reporting the onset of left mechanical hip pain since the 33rd week of pregnancy. After delivery, similar complaints emerged on the right side. Hip X-ray showed a decrease in bone density in the left hip. Later, Magnetic Resonance Imaging revealed bilateral bone marrow edema in both proximal femurs. The diagnosis of TOH was established, and the patient was treated with conservative measures. Seven months later, she was asymptomatic. Pregnancy is a recognized risk factor for TOH, especially in the last trimester. It is an important differential diagnosis to consider in cases of hip pain in pregnant or newly breastfeeding women.

Predictive factors of fragility fractures and associated mortality: assessment of patients observed at emergency department.

AIM: To assess the predictive factors for a subsequent fragility fracture (FF) and mortality. METHODS: Retrospective monocentric study including patients observed at the emergency department (ED) of a referral hospital with a FF, between 1st January 2017 and 31st December 2018. Fractures events were identified through discharge codes using the 9th International Classification of Diseases codes and FF were adjudicated after revision of the clinical files. We identified 1673 patients with FF. After calculating a representative sample (95% confidence interval), 172 hip, 173 wrist and 112 vertebral fractures were included in the analysis. Their clinical files were reviewed until 31st December 2020. A multivariate analysis was performed in order to identify predictive factors for FF. RESULTS: Overall, during the follow-up period 76 patients (16.6%) had a new FF and 120 patients (26.3%) died. Multivariate analysis showed that previous visits to the ED due to falls (p=0.002) and malignancy (p=0.026) were independent risk factors for a new FF. The main predictors of mortality were age, hip fracture, oral corticosteroid treatment, normal or low BMI and cardiac, neurologic or chronic kidney disease. CONCLUSIONS: FF are a very prevalent public health problem that can lead to significant morbidity and death. Certain comorbidities seem to be associated with new FF and increased mortality. There might be a substantial missed opportunity for intervention in these patients, namely in ED visits.

Barriers and alternatives to pediatric rheumatology referrals: a survey of family doctors and pediatricians in Portugal.

BACKGROUND: Access to pediatric rheumatology (PR) is not well described in Portugal. The main goal of this study was to ascertain barriers to PR referrals and subsequent alternative referral patterns among family doctors and pediatricians. METHODS: A web-based survey was e-mailed to family doctors and pediatricians practicing in Portugal, in order to investigate access to PR care issues. Descriptive and comparative analysis was performed. RESULTS: Two hundred and ninety-two responses were obtained, 24.7% from pediatricians and 75.3% from family doctors. Only 12% claimed to have had specific education on PR. Nearly 70% worked less than one hour away from a PR center. Twenty eight percent had referred a patient to PR at least once, and 9.3% experienced a situation in which they considered referring to PR but ultimately did not. Many referred to other specialties, primarily pediatrics, adult rheumatology, and pediatric orthopedics. Pediatricians encountered more diversified rheumatic diseases. Fifty five percent had no opinion on PR centers' support, while 24% found it sufficient. Having specific training on PR, being a pediatrician and a specialist were associated with greater referrals to PR. The most rated measure for PR referrals' improvement was promoting education. Regional access to PR's discrepancies were documented. CONCLUSION: Mainly lack of education on PR, but also uneven national coverage and greater distances to some PR centers were the main barriers to PR referrals, in Portugal. Pediatricians seem to have better education, greater experience and more referrals to PR. The current alternatives for referral are pediatrics, adult rheumatology and pediatric orthopedics. Educational consolidation was the biggest and most rewarding inconsistency to battle against.

Cycling versus swapping strategies in psoriatic arthritis: results from the rheumatic diseases Portuguese register.

OBJECTIVE: To compare the 2-year retention rate between a second tumor necrosis factor alpha inhibitor (TNFi) and secukinumab (SEK) or ustekinumab (UST), in Psoriatic Arthritis (PsA) patients with previous inadequate response to their first TNFi. METHODS: Prospective longitudinal cohort study with a follow-up period of 2 years using the Nationwide Portuguese Reuma.pt database. Patients with a clinical diagnosis of PsA who also fulfill the CASPAR classification criteria, with previous treatment failure to a first-line TNFi and having started a second biotechnological drug (TNFi, SEK or UST) were included. The Cycling group was defined as switching from a first TNFi to a second TNFi, and the Swapping group as switching from a first TNFi to SEK or UST. Sociodemographic data, disease characteristics, disease activity scores and physical function at baseline and after 6, 12 and 24 months were recorded. Cox-proportional hazards regression was used to compare retention rates between Cycling and Swapping groups. To obtain a predictor model of 2-year discontinuation, a multivariable Cox regression model was performed. RESULTS: In total, 439 patients were included, 58% were female, with a mean age (standard deviation) of 49 (12) years. Globally, 75.6% initiated a second TNFi (Cycling group), and 24.4% started SEK/UST (Swapping group). The retention rates after 6, 12 and 24 months were 72%/66%/59% in the Cycling group; and 77%/66%/59% in the Swapping group. There were no significant differences in retention rates between both strategies (HR: 1.06, 95% CI 0.72-1.16). After 2 years of follow-up, 34.4% of patients discontinued their second biologic, mainly due to inefficacy (72.8%), with no differences found between groups. Baseline treatment with glucocorticoids was the only predictor of discontinuation after 2 years of follow-up (HR:1.668, 95% CI 1.154-2.409). CONCLUSIONS: After failure of a first TNF inhibitor, Cycling and Swapping strategies result in similar retention rates suggesting that both are acceptable in the management of patients with psoriatic arthritis.

Banded RYGB Ring Slippage Endoscopic Removal with Self-expandable Stents: a Comparative Study Between Metallic and Plastic One.

PURPOSE: Banded Roux-en-Y gastric bypass (RYGB) was a common bariatric procedure in the 2000s, and the ring slippage is one of its late adverse events. Both plastic and metallic stents have been reported as adjunct methods to induce erosion and facilitate endoscopic removal of the ring. OBJECTIVE: To compare the safety and effectiveness of self-expanding metallic stents (SEMS) and plastic stents (SEPS) to treat ring slippage. MATERIALS AND METHODS: We conducted a retrospective longitudinal study analyzing consecutive patients with ring dysfunction treated with stents plus endoscopic removal. RESULTS: Ninety patients were enrolled (36 SEMS vs. 54 SEPS). The mean age was 48.56 ± 13.07 and 45.6 ± 12.1 in the SEMS and SEPS groups, respectively. All patients had band slippage, but 24 from SEMS group and 23 from SEPS group had further complications. There were more complications in metallic stent concerning mean absolute number of therapy-related adverse events (1.33 ± 0.48 vs. 1.72 ± 0.5, p > 0.05) and time until erosion (14.9 ± 1.6 vs. 13.8 ± 1.4 days, p > 0.05). Female sex and age > 41 years old correlated with longer time to band erosion and higher incidence of adverse events in SEMS patients. In SEPS group, only female sex was a risk factor for adverse events. CONCLUSION: Both procedures were efficient at inducing band erosion with similar safety profiles. Older and female patients are at a higher risk of treatment-related adverse events, especially those receiving SEMS.

4th Generation Biomaterials Based on PVDF-Hydroxyapatite Composites Produced by Electrospinning: Processing and Characterization.

Biomaterials that effectively act in biological systems, as in treatment and healing of damaged or lost tissues, must be able to mimic the properties of the body's natural tissues in its various aspects (chemical, physical, mechanical and surface). These characteristics influence cell adhesion and proliferation and are crucial for the success of the treatment for which a biomaterial will be required. In this context, the electrospinning process has gained prominence in obtaining fibers of micro- and nanometric sizes from polymeric solutions aiming to produce scaffolds for tissue engineering. In this manuscript, poly(vinylidene fluoride) (PVDF) was used as a polymeric matrix for the manufacture of piezoelectric scaffolds, exploring the formation of the ß-PVDF piezoelectric phase. Micro- and nanometric hydroxyapatite (HA) particles were incorporated as a dispersed phase in this matrix, aiming to produce multifunctional composite membranes also with bioactive properties. The results show that it is possible to produce membranes containing micro- and nanofibers of the composite by the electrospinning process. The HA particles show good dispersion in the polymer matrix and predominance of ß-PVDF phase. Also, the composite showed apatite growth on its surface after 21 days of immersion in simulated body fluid (SBF). Tests performed on human fibroblasts culture revealed that the electrospun membranes have low cytotoxicity attesting that the composite shows great potential to be used in biomedical applications as bone substitutions and wound healing.

Effectiveness and safety of original and biosimilar etanercept (Enbrel® vs Benepali®) in bDMARD-naïve patients in a real-world cohort of Portugal.

OBJECTIVE: To compare the effectiveness and safety of original (Enbrel®) and biosimilar (Benepali®) etanercept in Biologic Disease-modifying Antirheumatic Drug (bDMARD)-naïve patients, measured by persistence rates over 36 months of follow-up. METHODS: A retrospective multicentre observational study using data collected prospectively from The Rheumatic Diseases Portuguese Registry (Reuma.pt) was performed, including patients with: age ≥ 18 years old; diagnosis of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) or Spondyloarthritis (SpA) (axial or peripheral) with active disease and biologic-naïve who initiated treatment with etanercept as the first line biological treatment after 2010. Kaplan-Meyer and Cox regression were used to calculate the persistence rate in treatment. Disease activity at baseline and follow-up data at 6, 12, 18 and 24 months of treatment were compared. Causes for discontinuing therapy were summarized using descriptive statistics. Statistical significance was assumed for 2-sided p-values <0.05. RESULTS: We included 1693 patients (413 on Benepali® and 1280 on Enbrel®): 864 diagnosed with RA, 335 with PsA and 494 with SpA. The 3-year persistence rates were not significantly different between both treatment groups in RA, PsA and SpA patients. In the adjusted Cox model, hazard ratios of discontinuation were not statistically different (p>0.05). The proportion of subjects in remission or low disease activity in each disease was similar in both groups. Overall, 535 (31.6%) patients discontinued etanercept (428 patients on Enbrel® and 107 patients on Benepali®). The major cause of discontinuation was inefficacy (57.8%). No differences for the occurrence of inefficacy or adverse effects were found between treatment groups. CONCLUSIONS: Benepali® and Enbrel® demonstrated similar effectiveness and safety in RA, PsA and SpA in our cohort of patients. These data corroborate that the original and biosimilar drugs have similar quality characteristics and biological activity.

Portuguese recommendations for the use of biological and targeted synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis - 2020 update.

OBJECTIVE: To update the recommendations for the treatment of rheumatoid arthritis (RA) with biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs), endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists taking into account previous recommendations, new literature evidence and consensus opinion. At a national meeting, in a virtual format, three of the ten previous recommendations were re-addressed and discussed after a more focused literature review. A first draft of the updated recommendations was elaborated by a team of SPR rheumatologists from the SPR rheumatoid arthritis study group, GEAR. The resulting document circulated among all SPR rheumatologists for discussion and input. The level of agreement with each of all the recommendations was anonymously voted online by all SPR rheumatologists. RESULTS: These recommendations cover general aspects such as shared decision, treatment objectives, systematic assessment of disease activity and burden and its registry in Reuma.pt. Consensus was also achieved regarding specific aspects such as initiation of bDMARDs and tsDMARDs, assessment of treatment response, switching and definition of persistent remission. CONCLUSION: These recommendations may be used for guidance of treatment with bDMARDs and tsDMARDs in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.

Immunoregulatory and Effector Activities in Human Cutaneous and Mucosal Leishmaniasis: Understanding Mechanisms of Pathology.

Individuals infected with Leishmania braziliensis may develop the relatively benign localized cutaneous (CL) form or the mucosal (ML) form of the disease, which represents a more severe and mutilating variation. Interaction between parasite and host cells, as well as the genetic background of the host, are important determinants of the immune response, which is critical in determining disease outcome. Our studies over the years have been designed to determine the immunoregulatory and effector functions that culminate in the formation of lesions in CL and ML disease and how these host response factors may be better understood for design of novel therapies and prophylaxis. By studying the immune response from CL and ML patients in both the peripheral blood and in situ, we have learned much concerning the dynamics of the host-pathogen interaction that leads to the development of CL and ML. We used multiparameter flow cytometry to study the immunoregulatory profiles of the peripheral blood leukocytes, as well as laser scanning confocal microscopy to examine in situ several aspects of the local response, including the intensity of the inflammatory infiltrate, the cellular composition, inflammatory and anti-inflammatory cytokine expression, and the expression of the effector cytotoxic molecule, granzyme A, in lesions from CL and ML patients. Moreover, the application of correlative analysis between these immunological parameters has helped shed light on disease progression in CL and ML. These findings are reviewed within the context of understanding cellular and molecular mechanisms associated with the development of pathology in these diseases through a comparative analysis of the clinical forms, CL and ML, as well as of studies derived from peripheral blood and lesions.

IL-10 and IL-10 receptor overexpression in oral giant cell lesions.

OBJECTIVE: Central giant cell lesions (CGCL) and peripheral giant cell lesions (PGCL) occur in the jaws and contain osteoclast-like giant cells and mononuclear cells positive for the macrophage marker CD68. The participation of immune-inflammatory mechanisms has been proposed in the lesions development. As IL-10 is one of the most important anti-inflammatory cytokines and it is also an inhibitory cytokine to macrophage function and bone resorption, the purpose of the present study was to investigate its expression together with its receptor (IL-10Rα) in CGCL and PGCL. STUDY DESIGN: Six fragments of CGCL and seven fragments of PGCL were obtained by surgical excision. Frozen specimens were cut and subjected to immunofluorescence staining using fluorescent-labeled anti-CD68, anti-IL-10, and anti-IL-10Rα monoclonal antibodies. Microscopic analyses were performed and the percentage of positive mononuclear and giant cells for each parameter was obtained. RESULTS: Our results revealed that all giant cells from CGCL and PGCL were CD68+ and IL-10Rα+ and that the majority was also positive for IL-10. More than 50% of the mononuclear cells from both lesions expressed IL-10Rα and the majority of these cells were CD68+ and IL-10+. CONCLUSION: Considering that IL-10 has inhibitory effects on the pathologic processes related to the development of the oral giant cell lesions, the high frequencies of cells producing this cytokine seems contradictory to these lesions growth. Investigation about the production of inflammatory cytokines as well as the IL-10 signaling pathways in oral giant cell lesions is required to elucidate the immunopathology of CGCL and PGCL.

ANCA-associated vasculitis in a patient with enteropathic spondylarthritis: a case report and literature review.

Coexistence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and inflammatory bowel disease (IBD) is rare (Sy et al. in Semin Arthritis Rheum 45:475-482, 2016). Nevertheless, we present a case of an AAV in a 53-year-old female with enteropathic spondylarthritis previously treated with tumor necrosis factor α inhibitors (TNFi). Management of vasculitis in a patient with IBD may be problematic due to the difficulty in distinguishing if the vasculitis is an extraintestinal manifestation of the IBD or a new coexistent entity. Moreover, in our report, the previous treatment with TNFi is a possible confounding factor due to the paradoxical effects induced by TNFi, including vasculitis (Ramos-Casals et al. in Curr Rheumatol Rep 10:442-448, 2008). The reported case alerts to the complexity in the management of patients with enteropathic spondylarthritis and vasculitis, as well as discusses the diversity of differential diagnosis in this particular clinical scenario.

Ultrasound-guided core biopsy of the parotid gland: the procedure from the Rheumatology point of view.

Ultrasound-guided core biopsy is a minimally invasive technique able to identify lymphoma accompanying Sjögren syndrome, neoplasms or infiltrative diseases, with less complications compared to open biopsy. With these images, we aim to describe the ultrasound-guided core biopsy procedure, in a female patient with rheumatoid arthritis who presented evident inhomogeneity of the parotid gland. The procedure was performed by rheumatologists, trained in ultrasonography of the salivary glands, demonstrating that ultrasound-guided core biopsy is an easy and safe method to obtain salivary gland tissue.