From Psoriasis to Psoriatic Arthritis: Ultrasound Insights Connecting Psoriasis with Subclinical Musculoskeletal Inflammation and the Path to Psoriatic Arthritis.

PURPOSE OF REVIEW: This review summarizes the literature about the transition from psoriasis to psoriatic arthritis (PsA), focusing on musculoskeletal ultrasound (MSUS) for detecting subclinical inflammation and its role in diagnosis and triage of high-risk patients. RECENT FINDINGS: MSUS effectively detects subclinical musculoskeletal inflammation in patients with psoriasis; however, some of these lesions are non-specific and can be found in healthy individuals. Preliminary evidence suggest that subclinical sonographic findings may predict progression to PsA in psoriasis patients. MSUS can also improve referrals' accuracy and its integration in the PsA classification criteria may improve early PsA detection. MSUS is a valuable tool for detecting subclinical abnormalities in psoriasis patients, which indicate an increased likelihood of progressing to PsA. Its integration into referral protocols and clinical use could improve PsA diagnosis. We propose an MSUS-inclusive algorithm for PsA referrals and triage, which requires validation. The potential of early intervention in reducing PsA progression in psoriasis patients with subclinical inflammation remains to be established.

Structure and Contact Angle in Sessile Droplets of Binary Mixtures of Lennard-Jones Chains: A Molecular Dynamics Study.

Molecular dynamics simulations were carried out to investigate cylindrical droplets consisting of binary mixtures of Lennard-Jones (LJ) fluids in contact with a solid substrate. The droplets are composed of mixtures of the monomeric LJ fluid plus linear-tangent chains of 2, 10, 20, and 30 segments per chain that interact through a harmonic potential and the spherically truncated and shifted potential Lennard-Jones. The solid surface was modeled as a semi-infinite platinum substrate with an FCC structure that interacts with the fluid by means of a LJ 9-3 potential. We place emphasis on the effect of mixing a monomeric LJ fluid with heavy components on the contact angle and on the droplet structure, especially in the liquid-solid region. The density profiles of the droplets reveal a strong discrete layering of the fluid in the vicinity of the solid-liquid interface. The layering is more pronounced at low temperatures and for mixtures of short chains (symmetric mixtures). The ordering of the fluid was much less intense for fluids of long chains (asymmetric mixtures), and some cases even show gas enrichment at the solid-liquid interface. Enrichment at the vapor-liquid interfaces and density inversion can also be observed. However, these effects are not as marked as in planar interfaces. The contact angle between the droplet and the substrate is calculated by fitting an ellipse to the vapor-liquid interface defined by the Gibbs dividing surface. In general, an increment in the concentration of the heavy component and a reduction of the temperature resulted in an increase of the contact angle, which in turn disfavored the wetting of the droplet.

Interfacial properties of binary mixtures of Lennard-Jones chains in planar interfaces by molecular dynamics simulation.

Binary mixtures of fully flexible linear tangent chains composed of bonded Lennard-Jones interaction sites (monomers) were studied using the molecular dynamics simulation in the NVT ensemble. Their interfacial properties were investigated in planar interfaces by direct simulation of an explicit liquid film in equilibrium with its vapor. A method for the calculation of long-range interactions in inhomogeneous fluids was implemented to take into account the potential truncation effects. Surface tension and the pressure tensor were calculated via the classical Irving-Kirkwood method; vapor pressure, orthobaric densities, density profiles, and Gibbs relative adsorption of the volatile component with respect to the heavy component were also obtained. The properties were studied as a function of the temperature, molar concentration of the heavy component, and the asymmetry of the mixture. According to the results of this work, the temperature loses influence on the surface tension, vapor pressure, and Gibbs relative adsorption curves as the molecular length of the heavy component increases. This suggests that the universal behavior observed in pure fluids of Lennard-Jones chains also holds for binary mixtures. The contribution of the long-range interactions turned out to account for about 60%, 20%, and 10% of the surface tension, vapor pressure, and orthobaric density final values, respectively. This contribution was even larger at high temperatures and for large molecules. Strong enrichment of the volatile component at the interface was observed in the asymmetric mixtures. One of these mixtures even showed a barotropic effect at elevated pressures and a class III phase behavior.

Results of a global, patient-based survey assessing the impact of psoriatic arthritis discussed in the context of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory musculoskeletal disease, manifesting as peripheral arthritis, enthesitis, dactylitis, spondylitis, and skin and nail psoriasis. A core set of domains for measuring the impact of PsA has been developed, including pain, patient global assessment, physical function, health-related quality of life (HRQoL), and fatigue. To understand the impact of PsA on health domains from a patient's perspective, a global survey was developed and results reported in the context of the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire. METHODS: An online patient-based global survey was conducted by The Harris Poll in Australia, Brazil, Canada, France, Spain, Taiwan, the UK, and the US between November 2, 2017 and March 12, 2018. Eligible patients were ≥ 18 years old with a diagnosis of PsA for > 1 year, had visited a rheumatologist/dermatologist in the past 12 months and reported using ≥ 1 synthetic/biologic disease-modifying antirheumatic drug for PsA. Patients reported on PsA severity and symptoms, and the impact of PsA on HRQoL. After survey completion, responses were aligned with PsAID health domains. Descriptive statistics and chi-square tests were conducted. RESULTS: This analysis included 1286 patients from eight countries. Most patients (97%) reported musculoskeletal symptoms relating to PsA in the past year. Common moderate/major impacts of PsA were on physical activity (78%), ability to perform certain activities (76%), work productivity (62%), and career path (57%). Skin/nail symptoms occurred in 80% of patients. Overall, 69% of patients reported that PsA had a moderate/major impact on emotional/mental wellbeing, 56% on romantic relationships/intimacy, and 44% on relationships with family and friends. Social impacts included emotional distress (58%), social shame or disapproval (32%), and ceased participation in social activities (45%). Over half of all patients experienced unusual fatigue over the past 12 months (52%). The health domains that patients reported as being impacted by PsA aligned with life impact domains of the patient-derived PsAID health domains. CONCLUSION: These results highlight the impact of PsA on multiple health domains from a patient perspective that should be considered during shared decision-making processes between healthcare providers and patients.

Athenolide A, a New Steroidal Lactone from the Leaves of Athenaea martiana (Solanaceae) Determined by Means of HPLC-HR-MS-SPE-NMR Analysis.

Athenaea (Solanaceae) is an endemic genus belonging to the Brazilian Atlantic Rainforest. Recently, botanical investigations suggested the re-evaluation of the generic status of the genus Athenaea as a synonym of Aureliana. In this study, the first investigation of the Athenaea genus performed on Athenaea martiana by means of HPLC-HR-MS-SPE-NMR combined with high-resolution radical scavenging profile led to identification of several phenolic acids as radical scavengers: protocatechuic acid (1), 4-hydroxybenzoic acid (2), caffeic acid (3), vanillic acid (4), and ferulic acid (6). Additional analysis revealed a new steroidal lactone, named athenolide A (9). Their structures were elucidated by extensive use of NMR spectroscopy as well as HR-MS. Chemotaxonomic considerations based on these results supported the chemical relationships between the Athenaea and Aureliana genera, in agreement with the recent botanical findings.

The correlation between carotid artery atherosclerosis and clinical ischemic heart disease in lupus patients.

AIM: The extent of subclinical atherosclerosis can be assessed by ultrasound measurement of carotid intima-media thickness (cIMT) and total plaque area (TPA). We aimed to investigate the correlation between measures of atherosclerosis as documented on imaging studies of the carotid vasculature and clinical coronary artery disease (CAD) in systemic lupus erythematosus (SLE). METHODS: The study patients were recruited from the University of Toronto prospective cohort of SLE patients. Patients who had a history of CAD were compared to those without CAD. TPA and cIMT were measured using high-resolution optimized ultrasound systems. Logistic regression models were used to investigate the strength of association between ultrasound measures of atherosclerosis and CAD. The strength of association as expressed by odds ratio (OR) was compared between TPA and cIMT. RESULTS: A total of 103 SLE patients were analyzed (27 patients with a history of CAD). Carotid IMT correlated only moderately with TPA (r = 0.43, p < 0.001). Both measures were significantly associated with the presence of CAD. However, TPA showed a stronger association than cIMT (OR 9.55 vs. 2.02, respectively). TPA was also more strongly associated with dyslipidemia and hypertension compared to cIMT. CONCLUSIONS: In SLE patients, cIMT correlates only moderately with TPA, suggesting that they measure different phenotypes of atherosclerosis. Carotid TPA correlated better than cIMT with cardiovascular risk factors and CAD, suggesting that it may serve as a better tool for the investigation of atherosclerosis in SLE.

The functional MICA-129 polymorphism is associated with skin but not joint manifestations of psoriatic disease independently of HLA-B and HLA-C.

A methionine/valine polymorphism at amino acid 129 of the major histocompatibility complex class I chain-related gene A (MICA-129) categorizes alleles into strong and weak binders of the natural killer (NK) and T-cell receptor NKG2D. We investigated whether MICA-129 is differentially associated with skin and joint manifestations of psoriatic disease (PsD) independently of human leukocyte antigen (HLA)-C and HLA-B in patients and controls from Toronto and St. John's. The MICA-129 methionine (Met) allele, particularly Met/Met homozygosity, was strongly associated with both cutaneous psoriasis (PsC) and psoriatic arthritis (PsA) independently of HLA-B and HLA-C in Toronto patients, and was also associated with PsA in St. John's patients, but with no additional effect of Met/Met homozygosity. No association remained after adjustment for HLA alleles in St. John's patients. MICA-129 was not associated with PsA when compared with PsC. We conclude that MICA-129 is a marker of skin manifestations of PsD that is independent of HLA class I in Toronto patients.

Damage in lupus patients--what have we learned so far?

With the improvement of survival of systemic lupus erythematosus (SLE) patients, prevention of organ damage has become a major goal in the management of these patients. The need for a reliable tool for assessment of cumulative damage over time led to the development of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI) that allowed a standardized measurement of damage and facilitated research in the field. Damage accumulates over the course of the disease; however, some patients do not accrue any damage even after many years. Damage accrues at a higher rate among patients with more active disease, highlighting the importance of prompt control of disease manifestations. However, medications administered to control disease activity, particularly corticosteroids, can also result in organ damage, emphasizing the need for adjustment of these agents as soon as disease is under control.

The use of ultrasound for the assessment of enthesitis in patients with spondyloarthritis.

Seronegative spondyloarthritis (SpA) represents a group of diseases that share certain genetic, clinical, and radiographic features. Enthesitis, inflammation at the site of tendon insertion into the bone, involving both the axial and the peripheral joints, is an important sign of SpA. Clinical diagnosis of enthesitis, however, is neither sensitive nor specific; thus, the diagnosis of enthesitis often relies on typical abnormalities in imaging studies. Due to its low costs and availability, ultrasound is emerging as the preferred technique for detection of enthesitis for both clinical and research purposes. Ultrasonographic features of enthesitis include tendon hypoechogenicity and thickening, calcifications, bone erosions, and Doppler signal. Several semi-quantitative scoring systems have been developed to quantify ultrasonographic abnormalities of the entheses. These methods have been used for early diagnosis and classification of SpA as well as for monitoring response to treatment.

Thromboelastometric detection of clotting Factor XIII deficiency in cardiac surgery patients.

AIM(S): In this article, we aimed to investigate plasma Factor XIII levels after extracorporeal circulation in cardiac surgery by thromboelastometric detection, as extracorporeal circulation causes various coagulation disorders due to the exposure of blood to artificial surfaces, inflammatory induction and mechanical destruction of platelets and coagulation factors, which may particularly affect factors with long half-lives, such as Factor XIII. BACKGROUND: Since transfusion algorithms are often empirical and laboratory analysis of Factor XIII plasma levels may not be available 24 h a day, bed-side testing using rotational thromboelastometry (ROTEM) could offer a splendid option to define the cause of excessive peri-operative bleeding disorders in general and Factor XIII levels in particular in a timely manner and thus facilitating exact substitution therapy. METHODS: In this trial, we investigated 25 cardiac surgery patients with extracorporeal bypass times over 100 min. Standard laboratory and ROTEM analyses were performed post-operatively at the time of intensive care unit admission and 6 h later. We implemented EXTEM with additional Factor XIII (teenTEM) as additional test by adding 0·625 IU Factor XIII to standard EXTEM reagents. RESULTS: In this observational study, we could not demonstrate a correlation between Factor XIII and MCFEXTEM , CFTEXTEM or MLEXTEM . Neither Factor XIII plasma levels nor MCFEXTEM could predict blood loss. In accordance with previous findings, we were able to demonstrate increased maximum clot firmness (MCF), decreased clot formation time and decreased maximum lysis by adding Factor XIII in vitro (teenTEM vs EXTEM) indicating an improvement in the coagulation process. As shown before, we also found a strong correlation between MCF and platelet and fibrinogen plasma levels. CONCLUSION: In summary, 'teenTEM' test does not seem to detect Factor XIII deficient patients in cardiac surgery. Furthermore, post-operative blood loss could not be predicted neither by ROTEM nor by laboratory analysis of Factor XIII. In vitro administration of Factor XIII appears to improve laboratory measures of haemostasis.

Ultradeformable archaeosomes as new topical adjuvants.

Ultradeformable archaeosomes (UDA) are vesicles made of soybean phosphatidylcholine (SPC), sodium cholate (NaChol) and polar lipids from Halorubrum tebenquichense (3:1:3 wt/wt). Although ultradeformable liposomes (UDL, made of SPC and NaChol at 6:1 wt/wt) and UDA were neither captured nor caused cytotoxicity on keratinocytes, UDA was avidly captured by macrophages, their viability being reduced by 0.4-1.6 mg/mL phospholipids by 25 to 60%. Instead, UDL were poorly captured and caused no toxicity. Balb/C mice immunized by the topical route with four doses of ovalbumin (OVA)-loaded UDA, at 75 µg OVA/600 µg phospholipids (125 nm mean size and -42 mV zeta potential), induced IgG titers tenfold to 100-fold higher than those immunized with OVA-loaded UDL at the same dosage. Both matrices penetrate to the same skin depth (nearly 10 µm after 1 hour on excised human skin), being the higher topical adjuvancy and higher phagocytic uptake of UDA related to its glycolipid content. FROM THE CLINICAL EDITOR: This work summarizes key findings related to the development of ultradeformable archaeosomes as vehicles utilized in transdermal delivery systems with improved skin penetration.

Negative predictive value of procalcitonin to rule out bacterial respiratory co-infection in critical covid-19 patients.

BACKGROUND: Procalcitonin (PCT) and C-Reactive Protein (CRP) are useful biomarkers to differentiate bacterial from viral or fungal infections, although the association between them and co-infection or mortality in COVID-19 remains unclear. METHODS: The study represents a retrospective cohort study of patients admitted for COVID-19 pneumonia to 84 ICUs from ten countries between (March 2020-January 2021). Primary outcome was to determine whether PCT or CRP at admission could predict community-acquired bacterial respiratory co-infection (BC) and its added clinical value by determining the best discriminating cut-off values. Secondary outcome was to investigate its association with mortality. To evaluate the main outcome, a binary logistic regression was performed. The area under the curve evaluated diagnostic performance for BC prediction. RESULTS: 4635 patients were included, 7.6% fulfilled BC diagnosis. PCT (0.25[IQR 0.1-0.7] versus 0.20[IQR 0.1-0.5]ng/mL, p<0.001) and CRP (14.8[IQR 8.2-23.8] versus 13.3 [7-21.7]mg/dL, p=0.01) were higher in BC group. Neither PCT nor CRP were independently associated with BC and both had a poor ability to predict BC (AUC for PCT 0.56, for CRP 0.54). Baseline values of PCT<0.3ng/mL, could be helpful to rule out BC (negative predictive value 91.1%) and PCT≥0.50ng/mL was associated with ICU mortality (OR 1.5,p<0.001). CONCLUSIONS: These biomarkers at ICU admission led to a poor ability to predict BC among patients with COVID-19 pneumonia. Baseline values of PCT<0.3ng/mL may be useful to rule out BC, providing clinicians a valuable tool to guide antibiotic stewardship and allowing the unjustified overuse of antibiotics observed during the pandemic, additionally PCT≥0.50ng/mL might predict worsening outcomes.

Clinical characteristics, systemic complications, and in-hospital outcomes for patients with COVID-19 in Latin America. LIVEN-Covid-19 study: A prospective, multicenter, multinational, cohort study.

PURPOSE: The COVID-19 pandemic has spread worldwide, and almost 396 million people have been infected around the globe. Latin American countries have been deeply affected, and there is a lack of data in this regard. This study aims to identify the clinical characteristics, in-hospital outcomes, and factors associated with ICU admission due to COVID-19. Furthermore, to describe the functional status of patients at hospital discharge after the acute episode of COVID-19. MATERIAL AND METHODS: This was a prospective, multicenter, multinational observational cohort study of subjects admitted to 22 hospitals within Latin America. Data were collected prospectively. Descriptive statistics were used to characterize patients, and multivariate regression was carried out to identify factors associated with severe COVID-19. RESULTS: A total of 3008 patients were included in the study. A total of 64.3% of patients had severe COVID-19 and were admitted to the ICU. Patients admitted to the ICU had a higher mean (SD) 4C score (10 [3] vs. 7 [3)], p<0.001). The risk factors independently associated with progression to ICU admission were age, shortness of breath, and obesity. In-hospital mortality was 24.1%, whereas the ICU mortality rate was 35.1%. Most patients had equal self-care ability at discharge 43.8%; however, ICU patients had worse self-care ability at hospital discharge (25.7% [497/1934] vs. 3.7% [40/1074], p<0.001). CONCLUSIONS: This study confirms that patients with SARS CoV-2 in the Latin American population had a lower mortality rate than previously reported. Systemic complications are frequent in patients admitted to the ICU due to COVID-19, as previously described in high-income countries.

Differential major histocompatibility complex class I chain-related A allele associations with skin and joint manifestations of psoriatic disease.

About 30% of patients with psoriasis have psoriatic arthritis (PsA), an inflammatory arthritis that can affect both axial and peripheral joints. Major histocompatibility complex class I chain-related A (MICA) alleles have previously been shown to be associated with PsA; however it is unclear whether there is a differential association of MICA alleles with skin and joint manifestations of PsA. Here, we describe a case-control study that aims to validate previously reported MICA allele associations with PsA and determine whether MICA alleles differentiate patients with PsA from those with psoriasis without PsA. Two hundred forty-nine unrelated Caucasian PsA patients, 243 psoriasis patients without arthritis, and 248 healthy controls were genotyped for 55 MICA alleles using PCR-SSP, and for human leucocyte antigen (HLA)-B and HLA-C alleles by PCR-SSO reverse line blot. Allele frequencies were calculated and logistic regressions were performed, adjusting for HLA-B and HLA-C alleles previously shown to be associated with psoriasis and/or PsA. Several MICA alleles were associated with psoriatic disease, PsA, and psoriasis compared with controls, and PsA compared with psoriasis in univariate analyses. Haplotype analysis showed evidence of strong linkage disequilibrium (LD) between PsA and psoriasis risk alleles of HLA-C, HLA-B, and MICA. After adjusting for significant HLA-B and HLA-C alleles in multivariate analyses, MICA*016 remained significantly associated with psoriasis [odds ratio (OR) = 5.5, P = 0.008]. MICA*00801 homozygosity was associated with susceptibility to PsA when compared with patients with psoriasis alone (OR = 2.26, P = 0.009). We conclude that most MICA allele associations with psoriasis and PsA are dependent on LD with HLA-B and HLA-C risk alleles. Independent of HLA, only MICA*016 influences the risk of developing psoriasis without arthritis, and homozygosity for MICA*00801 increases the risk of developing PsA in patients with psoriasis.

Burden of invasive pneumococcal disease (IPD) over a 10-year period in Bogotá, Colombia.

BACKGROUND: Invasive pneumococcal disease (IPD) is the leading cause of infectious death worldwide. This study aimed to describe the epidemiology of IPD and the impact of pneumococcal conjugate vaccine-10 (PCV-10) over a 10-year period in Bogotá, Colombia. METHODS: This was a laboratory-based surveillance study of Streptococcus pneumoniae isolated from patients with IPD from 82 hospitals over 10 years in Bogotá, Colombia. Data were compared between two periods: 2007-2011 (before the introduction of PCV-10) and 2012-2017 (after the introduction of PCV-10). RESULTS: In total, 1670 patients with IPD were included in the study between 2007 and 2017. Between 2007 and 2011, the most common serotypes were 14, 1, 6B, 6A and 3. Between 2012 and 2017, the most common serotypes were 19A, 3, 14 and 1. A decrease in the incidence of IPD, particularly in children aged 0-4 years, was noted after the introduction of PCV-10. Importantly, this reduction in incidence was not observed in patients aged ≥50 years. CONCLUSIONS: The IPD burden in Bogotá remained stable between 2007 and 2017. The incidence of IPD decreased in children but not in older adults. The introduction of PCV-10 led to a change in the most prevalent serotypes to serotypes that are not included in PCV-10.

Imiquimod-loaded nanoarchaeosomes as a promising immunotherapy against Trypanosoma cruzi infection.

The purpose of this study was to evaluate the efficacy of imiquimod-containing nanovesicles prepared with lipids extracted from the hyperhalophile archaebacterium Halorubrum tebenquichense (nanoARC-IMQ) to induce protection against Trypanosoma cruzi infection. The therapeutic efficacy of archaeolipid nanovesicles was assessed in an experimental murine model of acute infection with T. cruzi. The administration of nanoARQ-IMQ prevented mortality as compared to infected untreated animals, reduced parasitemia levels and diminished myocardial and musculoskeletal lesions in mice infected with a lethal strain of T. cruzi. Our findings suggest that the immunotherapy with nanoARC-IMQ has potential to limit the progression of Chagas disease.

Archaeosomes made of Halorubrum tebenquichense total polar lipids: a new source of adjuvancy.

BACKGROUND: Archaeosomes (ARC), vesicles prepared from total polar lipids (TPL) extracted from selected genera and species from the Archaea domain, elicit both antibody and cell-mediated immunity to the entrapped antigen, as well as efficient cross priming of exogenous antigens, evoking a profound memory response. Screening for unexplored Archaea genus as new sources of adjuvancy, here we report the presence of two new Halorubrum tebenquichense strains isolated from grey crystals (GC) and black mood (BM) strata from a littoral Argentinean Patagonia salt flat. Cytotoxicity, intracellular transit and immune response induced by two subcutaneous (sc) administrations (days 0 and 21) with BSA entrapped in ARC made of TPL either form BM (ARC-BM) and from GC (ARC-GC) at 2% w/w (BSA/lipids), to C3H/HeN mice (25 microg BSA, 1.3 mg of archaeal lipids per mouse) and boosted on day 180 with 25 microg of bare BSA, were determined. RESULTS: DNA G+C content (59.5 and 61.7% mol BM and GC, respectively), 16S rDNA sequentiation, DNA-DNA hybridization, arbitrarily primed fingerprint assay and biochemical data confirmed that BM and GC isolates were two non-previously described strains of H. tebenquichense. Both multilamellar ARC mean size were 564 +/- 22 nm, with -50 mV zeta-potential, and were not cytotoxic on Vero cells up to 1 mg/ml and up to 0.1 mg/ml of lipids on J-774 macrophages (XTT method). ARC inner aqueous content remained inside the phago-lysosomal system of J-774 cells beyond the first incubation hour at 37 degrees C, as revealed by pyranine loaded in ARC. Upon subcutaneous immunization of C3H/HeN mice, BSA entrapped in ARC-BM or ARC-GC elicited a strong and sustained primary antibody response, as well as improved specific humoral immunity after boosting with the bare antigen. Both IgG1 and IgG2a enhanced antibody titers could be demonstrated in long-term (200 days) recall suggesting induction of a mixed Th1/Th2 response. CONCLUSION: We herein report the finding of new H. tebenquichense non alkaliphilic strains in Argentinean Patagonia together with the adjuvant properties of ARC after sc administration in mice. Our results indicate that archaeosomes prepared with TPL from these two strains could be successfully used as vaccine delivery vehicles.

From ankylosis to pencil-in-cup deformity in psoriatic arthritis: a case report.

A 56-year-old woman with psoriatic arthritis is presented whose initially ankylosed digit was later found to develop pencil-in-cup change. The patient was treated over that period with etanercept and had no signs of active arthritis. The possible mechanisms for these changes are discussed.