Personalized Axial Spondyloarthritis Care

Abstract

Purpose of review

To discuss the personalized care of patients with axial spondyloarthritis.

Recent findings

Secukinumab, an IL-17A inhibitor, has recently been proven to be effective in treating signs and symptoms of ankylosing spondylitis. The latest update of ASAS/EULAR management recommendations include secukinumab and recommend a personalized medicine approach for the treatment of patients with axial spondyloarthritis.

Summary

Nonsteroidal anti-inflammatory drugs benefit a significant proportion of patients with axial spondyloarthritis. Conventional disease-modifying anti-rheumatic drugs are not effective for axial symptoms. Sulfasalazine may have limited efficacy for peripheral articular symptoms, but not for enthesitis. Local glucocorticoid injections may be helpful for joint and entheseal inflammation. Patients failing to respond to conventional treatments can be treated with biologics inhibiting TNF-α and IL-17A. They all have a similar efficacy for the treatment of axial and peripheral disease but vary in their efficacy on the extra-articular disease manifestations and safety profiles. TNF-α inhibitors are recommended over secukinumab as the initial choice for biologic treatment, due to the availability of larger amount of data, as well as longer and greater clinical experience with these agents. Molecular and genomic biomarkers which are central and crucial to implementation of personalized medicine in its modern context are not yet available for the treatment of axial spondyloarthritis; therefore, personalized care of such patients can currently be practiced mainly on the basis of general patient characteristics, patient preferences, and clinical findings.

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Prognostic factors of a favorable outcome following a supervised exercise program for soldiers with sub-acute and chronic low back pain

Abstract

Background

Low back pain (LBP) encompasses heterogeneous patients unlikely to respond to a unique treatment. Identifying sub-groups of LBP may help to improve treatment outcomes. This is a hypothesis-setting study designed to create a clinical prediction rule (CPR) that will predict favorable outcomes in soldiers with sub-acute and chronic LBP participating in a multi-station exercise program.

Methods

Military members with LBP participated in a supervised program comprising 7 stations each consisting of exercises of increasing difficulty. Demographic, impairment and disability data were collected at baseline. The modified Oswestry Disability Index (ODI) was administered at baseline and following the 6-week program. An improvement of 50% in the initial ODI score was considered the reference standard to determine a favorable outcome. Univariate associations with favorable outcome were tested using chi-square or paired t-tests. Variables that showed between-group (favorable/unfavorable) differences were entered into a logistic regression after determining the sampling adequacy. Finally, continuous variables were dichotomized and the sensitivity, specificity and positive and negative likelihood ratios were determined for the model and for each variable.

Results

A sample of 85 participants was included in analyses. Five variables contributed to prediction of a favorable outcome: no pain in lying down (p = 0.017), no use of antidepressants (p = 0.061), FABQ work score < 22.5 (p = 0.061), fewer than 5 physiotherapy sessions before entering the program (p = 0.144) and less than 6 months' work restriction (p = 0.161). This model yielded a sensitivity of 0.78, specificity of 0.80, LR+ of 3.88, and LR- of 0.28. A 77.5% probability of favorable outcome can be predicted by the presence of more than three of the five variables, while an 80% probability of unfavorable outcome can be expected if only three or fewer variables are present.

Conclusion

The use of prognostic factors may guide clinicians in identifying soldiers with LBP most likely to have a favorable outcome. Further validation studies are needed to determine if the variables identified in our study are treatment effect modifiers that can predict success following participation in the multi-station exercise program.

Trial registration

ClinicalTrials.gov Identifier: NCT03464877 registered retrospectively on 14 March 2018.

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HAA1 and PRS3 overexpression boosts yeast tolerance towards acetic acid improving xylose or glucose consumption: unravelling the underlying mechanisms

Abstract

Acetic acid tolerance and xylose consumption are desirable traits for yeast strains used in industrial biotechnological processes. In this work, overexpression of a weak acid stress transcriptional activator encoded by the gene HAA1 and a phosphoribosyl pyrophosphate synthetase encoded by PRS3 in a recombinant industrial Saccharomyces cerevisiae strain containing a xylose metabolic pathway was evaluated in the presence of acetic acid in xylose- or glucose-containing media. HAA1 or PRS3 overexpression resulted in superior yeast growth and higher sugar consumption capacities in the presence of 4 g/L acetic acid, and a positive synergistic effect resulted from the simultaneous overexpression of both genes. Overexpressing these genes also improved yeast adaptation to a non-detoxified hardwood hydrolysate with a high acetic acid content. Furthermore, the overexpression of HAA1 and/or PRS3 was found to increase the robustness of yeast cell wall when challenged with acetic acid stress, suggesting the involvement of the modulation of the cell wall integrity pathway. This study clearly shows HAA1 and/or, for the first time, PRS3 overexpression to play an important role in the improvement of industrial yeast tolerance towards acetic acid. The results expand the molecular toolbox and add to the current understanding of the mechanisms involved in higher acetic acid tolerance, paving the way for the further development of more efficient industrial processes.

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Revision of Protohydnum (Auriculariales, Basidiomycota)

Abstract

Three species currently addressed to Protohydnum (Auriculariales) are studied with morphological and DNA methods. The genus Protohydnum is retained for the type species only, P. cartilagineum, recently re-collected in Brazil. The European species, P. piceicola, is not congeneric with P. cartilagineum and, therefore, placed in its own genus, Hyalodon, gen. nov. Another Hyalodon species, H. antui, is described from East Asia. The third member of Protohydnum sensu lato, P. sclerodontium from South-East Asia, is transferred to Elmerina.

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Silicone wristbands compared with traditional polycyclic aromatic hydrocarbon exposure assessment methods

Abstract

Currently there is a lack of inexpensive, easy-to-use technology to evaluate human exposure to environmental chemicals, including polycyclic aromatic hydrocarbons (PAHs). This is the first study in which silicone wristbands were deployed alongside two traditional personal PAH exposure assessment methods: active air monitoring with samplers (i.e., polyurethane foam (PUF) and filter) housed in backpacks, and biological sampling with urine. We demonstrate that wristbands worn for 48 h in a non-occupational setting recover semivolatile PAHs, and we compare levels of PAHs in wristbands to PAHs in PUFs-filters and to hydroxy-PAH (OH-PAH) biomarkers in urine. We deployed all samplers simultaneously for 48 h on 22 pregnant women in an established urban birth cohort. Each woman provided one spot urine sample at the end of the 48-h period. Wristbands recovered PAHs with similar detection frequencies to PUFs-filters. Of the 62 PAHs tested for in the 22 wristbands, 51 PAHs were detected in at least one wristband. In this cohort of pregnant women, we found more significant correlations between OH-PAHs and PAHs in wristbands than between OH-PAHs and PAHs in PUFs-filters. Only two comparisons between PAHs in PUFs-filters and OH-PAHs correlated significantly (r_s = 0.53 and p = 0.01; r_s = 0.44 and p = 0.04), whereas six comparisons between PAHs in wristbands and OH-PAHs correlated significantly (r_s = 0.44 to 0.76 and p = 0.04 to <0.0001). These results support the utility of wristbands as a biologically relevant exposure assessment tool which can be easily integrated into environmental health studies.

Graphical abstract

PAHs detected in samples collected from urban pregnant women

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Biological therapy downregulates the heterodimer S100A8/A9 (calprotectin) expression in psoriatic patients

Abstract

The pathophysiology of psoriasis is very complex and involves an interplay between immune cells and keratinocytes. The keratinocyte production of calprotectin (S100A8/A9), induced by the inflammatory psoriatic milieu, may be involved in initiating immune cell invasion, as well as in propagating inflammation. However, the exact role of calprotectin in psoriasis remains unclear. Therapeutic approaches utilizing adalimumab, etanercept and ustekinumab are widely used in psoriatic treatment, but their anti-inflammatory mechanisms are not fully understood. The aim of this study was to investigate, by immunohistochemical analysis, the expression of the heterocomplex S100A8/A9 in lesional skin from psoriatic patients undergoing biological therapy with adalimumab, etanercept or ustekinumab. Our results showed that S100A8/A9, absent or present at very low level in skin biopsies from healthy subjects, is dramatically upregulated in each epidermal layer from psoriatic patients. Interestingly, calprotectin was mainly localized in keratinocyte nuclei from psoriatic patients, suggesting a role of S100A8/A9 in keratinocyte nuclear function. Furthermore, we have shown that the biological treatment induced a drastic reduction of S100A8/A9 expression in skin biopsies from treated patients, correlating with PASI reduction. Our results suggest that calprotectin may play a crucial role as a significant marker of inflammation in psoriasis, and that its reduction of expression may be considered a favourable prognostic marker in psoriasis.

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GNAS-mutated carcinoma arising from gastric foveolar metaplasia in the duodenum after 9 years of observation

Abstract

This case involved an 80-year-old man. Screening with esophagogastroduodenoscopy (EGD) in 2004 revealed Brunner's gland hyperplasia (BGH), 5 mm in size, in the duodenal bulb. The size of the lesion increased and its shape has changed since then, as detected in subsequent EGDs. The lesion had increased in size to 15 mm with a depression and biopsy specimens revealed an adenocarcinoma. The patient underwent endoscopic mucosal resection. Histopathological assessments indicated an adenocarcinoma arising from gastric foveolar metaplasia (GFM) adjacent to BGH. BGH stained positive for MUC6, and GFM and the adenocarcinoma stained positive for MUC5AC. Mutations of the GNAS gene were not detected in the GFM biopsied in 2007. On the other hand, common GNAS mutations (R201H) were detected in GFM and the adenocarcinoma in the endoscopically resected specimen in 2013. Moreover, mutant allele frequencies were higher in the carcinoma than in GFM. The patient remains disease-free for 4 years after endoscopic treatment. This case report further supports the notion that GFM may be a precursor lesion in the process of GNAS-mutated, gastric-type duodenal carcinogenesis.

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