Systemic Scleroderma Induced by Nivolumab in Malignant Melanoma.

BACKGROUND: Immunotherapy using immune checkpoint inhibitors is not devoid of immune-related adverse events (irAEs) including rheumatological conditions. CASE REPORT: We report a rare case of a 47-year-old woman with metastatic melanoma who developed systemic scleroderma after initiating nivolumab. The patient displayed inflammatory arthralgias, morning stiffness, and classical cutaneous manifestations of the disease. Clinical evaluations also revealed carpal tunnel syndrome, cardiac involvement, and dyspnea. RNA-Polymerase III antibodies were positive. Nivolumab, an anti-PD-1 antibody, was considered as a potential trigger for this condition. CONCLUSION: To our knowledge, this is the first case of nivolumab-induced systemic scleroderma in the context of melanoma described in the literature that fulfills the classification criteria of the disease. This case underscores the need for increased awareness of immune-related adverse events in patients receiving immune checkpoint inhibitors, emphasizing timely intervention and further research.

Cross-perspectives on care pathways for painful osteoarthritis: A qualitative analysis in patients and healthcare professionals.

PURPOSE: To analyse and compare patients' and healthcare professionals' (HPs) perspectives concerning patient care pathways for painful osteoarthritis (OA). PATIENTS AND METHODS: We performed a qualitative study of two focus groups corresponding to eight patients with painful OA and eight HPs involved in OA management. RESULTS: Six key themes emerged from the interviews: (1) representations of OA, (2) OA pain, (3) quality of life, (4) care pathways, (5) actors involved in the care pathway, and (6) treatments. Both groups considered general practitioners, pharmacists and physiotherapists to be first-line HPs, and no well-defined OA specialist was identified. Patients and HPs reported similar difficulties concerning the adaptation of management to individual cases, late diagnosis and treatment, whereas only patients mentioned financial issues. Communication difficulties were identified as a major problem both between patients and HPs, and between HPs. Patients reported a lack of knowledge concerning pain and OA. The coordination between the various HPs is required, with education on both pain and OA. Several possible solutions were put forward by both patients and HPs. CONCLUSION: The care pathways of patients with painful OA are complex, with an unclear definition of the roles of the various HPs and suboptimal coordination. The role of HPs should be defined and collaboration between HPs developed.

Diet and Disease Activity in Patients with Axial Spondyloarthritis: SpondyloArthritis and NUTrition Study (SANUT).

Axial Spondyloarthritis (axSpA) patients with inflamed intestines have higher SpA activity. Diets that modulate microbiota may influence inflammation and SpA activity. Today, data concerning the impact of diet on SpA activity are scarce. SANUT was a single-center, noninterventional, cohort study that assessed dietetic profiles associated with SpA activity in axSpA. Demographic, clinical, SpA-related, quality of life (QoL), fatigue, physical activity, and dietary data were collected. SpA activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) and by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). We assessed whether high SpA activity was associated with nutriment consumption. Between 12 February 2018 and 12 February 2020, 278 patients participated. High SpA activity, as measured by ASDAS and BASDAI, was significantly associated with higher body mass index and waist circumference, negative HLA-B27, lower QoL, higher fatigue, and higher digestive-symptom scores. Furthermore, high SpA activity, as measured by BASDAI, was associated with female sex, smoking status, patients who were not actively employed, reduced physical activity, and high intake of ultra-transformed foods, while high SpA activity, as measured by ASDAS, was associated with low intake of omega-3 PUFAs and fiber. Therefore, low intakes of omega-3 PUFAs and fiber, and high intake of ultra-transformed foods, are associated with high SpA activity.

Complete Genome Sequence of Stenotrophomonas maltophilia 1800, a New Bacterial Strain with Potential for Bioremediation of Oil-Contaminated Environments.

Stenotrophomonas maltophilia strain 1800 was isolated from the effluent of an industrial oil refinery in Algeria. Its genome was sequenced using Illumina MiSeq (2 × 150-bp read pairs) and Oxford Nanopore (long reads) technologies and assembled using Unicycler. It is composed of one chromosome of 4.83 Mb.

Real-life golimumab persitence in patients with axial spondyloarthritis: post-hoc results of the prospective observational cohort study, GO-PRACTICE.

OBJECTIVES: To evaluate in clinical practice the persistence and safety of golimumab, together with the evolution of disease activity and patient reported outcomes, in adult patients with rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis (axSpA). This article focuses on the outcomes of golimumab treatment in axSpA patients. METHODS: Golimumab persistence 24 months after initial prescription (primary outcome) was assessed using Kaplan-Meier estimates. Secondary outcomes included evaluations of disease activity evolution (ASDAS and BASDAI), patient-reported outcomes (EQ-5D, SF-12 and HAQ), and golimumab's safety profile. RESULTS: Of 478 axSpA patients, 60.9% were biologic-naïve. Mean age and proportion of females were higher in biologics-pretreated patients (46.8 vs. 40.2 years, p<0.001 and 62.0% vs. 49.8%, p=0.009, respectively). Golimumab persistence at 24 months was 52.6% [95% CI 47.9-57.1%] in the axSpA cohort. It was 59.2% [95% CI 53.1-64.8%] and 42.7% [95% CI 35.3-49.8%] respectively, for biologics-naïve and biologics-pretreated patients (p<0.01), and 65.9% [95% CI 58.9-72.0%] and 41.5% [95% CI 35.2-47.6%], respectively for males and females (p<0.01). Reasons for golimumab discontinuation were primary non-response (37.4%), secondary non-response (24.8%) and intolerance (21.5%). Disease activity and patient reported outcomes improved significantly for those who persisted at 24 months and were higher for biologics-naïve patients. CONCLUSIONS: Golimumab persistence at 2 years in axSpA patients was 52.6%. Previous treatment with another biologic and female gender were associated with earlier discontinuation. Golimumab was a well-tolerated therapy for axSpA, with no new safety signals observed.

Water and soil contaminated by arsenic: the use of microorganisms and plants in bioremediation.

Owing to their roles in the arsenic (As) biogeochemical cycle, microorganisms and plants offer significant potential for developing innovative biotechnological applications able to remediate As pollutions. This possible use in bioremediation processes and phytomanagement is based on their ability to catalyse various biotransformation reactions leading to, e.g. the precipitation, dissolution, and sequestration of As, stabilisation in the root zone and shoot As removal. On the one hand, genomic studies of microorganisms and their communities are useful in understanding their metabolic activities and their interaction with As. On the other hand, our knowledge of molecular mechanisms and fate of As in plants has been improved by laboratory and field experiments. Such studies pave new avenues for developing environmentally friendly bioprocessing options targeting As, which worldwide represents a major risk to many ecosystems and human health.

Chronic pain and neuroinflammation.

In rheumatology, chronic pain most often sets in after a musculoskeletal injury. Its persistence is not always due to the progression of the initial injury, but in some cases to the onset of central sensitization. Much scientific data suggests that this central sensitization is caused by multiple complex interactions between the nervous system and immune system. Afferent nerve fibers carrying pain information are responsible for peripheral sensitization partly linked to inflammation molecules. These afferent fibers release neurotransmitters in the dorsal root ganglion and dorsal horn of the spinal cord, capable of activating microglia, which are the local immune cells. The activated microglia will produce pro-inflammatory cytokines, chemokines and neuropeptides capable of interacting with the second-order neuron, but also segmental and descending inhibitory neurons. This is referred to as neuroinflammation, which will amplify the hypersensitivity of second-order neurons, otherwise called central sensitization. This neuroinflammation will be able to reach the higher brain structures, which are involved in pain modulation and the emotional and cognitive aspects of pain. The aim of this update is to describe the pathophysiology of chronic pain, incorporating the latest scientific data on neuroplasticity and neuroinflammation.

Metatranscriptomic outlook on green and brown food webs in acid mine drainage.

Acid mine drainages (AMDs), metal-rich acidic effluents generated by mining activities, are colonized by prokaryotic and eukaryotic microorganisms widely distributed among different phyla. We compared metatranscriptomic data from two sampling stations in the Carnoulès AMD and from a third station in the nearby Amous River, focussing on processes involved in primary production and litter decomposition. A synergistic relationship between the green and brown food webs was favoured in the AMD sediments by the low carbon content and the availability of mineral nutrients: primary production of organic matter would benefit C-limited decomposers whose activity of organic matter mineralization would in turn profit primary producers. This balance could be locally disturbed by heterogeneous factors such as an input of plant debris from the riparian vegetation, strongly boosting the growth of Tremellales which would then outcompete primary producers. In the unpolluted Amous River on the contrary, the competition for limited mineral nutrients was dominated by the green food web, fish and bacterivorous protists having a positive effect on phytoplankton. These results suggest that in addition to direct effects of low pH and metal contamination, trophic conditions like carbon or mineral nutrient limitations also have a strong impact on assembly and activities of AMDs' microbial communities.

Characterisation of hydrocarbon degradation, biosurfactant production, and biofilm formation in Serratia sp. Tan611: a new strain isolated from industrially contaminated environment in Algeria.

A novel bacterial strain was isolated from industrially contaminated waste water. In the presence of crude oil, this strain was shown to reduce the rate of total petroleum hydrocarbons (TPH) up to 97.10% in 24 h. This bacterium was subsequently identified by 16S rRNA gene sequence analysis and affiliated to the Serratia genus by the RDP classifier. Its genome was sequenced and annotated, and genes coding for catechol 1,2 dioxygenase and naphthalene 1,2-dioxygenase system involved in aromatic hydrocarbon catabolism, and LadA-type monooxygenases involved in alkane degradation, were identified. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of crude oil after biological treatment showed that Serratia sp. Tan611 strain was able to degrade n-alkanes (from C13 to C25). This bacterium was also shown to produce a biosurfactant, the emulsification index (E24) reaching 43.47% and 65.22%, against vegetable and crude oil, respectively. Finally, the formation of a biofilm was increased in the presence of crude oil. These observations make Serratia sp. Tan611 a good candidate for hydrocarbon bioremediation.

Real-life persistence of golimumab in patients with chronic inflammatory rheumatic diseases: results of the 2-year observational GO-PRACTICE study.

OBJECTIVES: GO-PRACTICE aimed to evaluate the persistence, clinical response and safety of golimumab in adult patients with chronic inflammatory rheumatic disease. METHODS: Prospective observational study with 24 months of follow-up, involving 134 rheumatologists from public or private health establishments in France. The primary outcome was the persistence of golimumab 24 months after initial prescription. Cumulative persistence probabilities were determined from Kaplan-Meier estimates. Secondary outcomes included an evaluation of disease activity and golimumab safety profile. RESULTS: Of 754 consecutively recruited patients, 170 had rheumatoid arthritis (RA) (54.3 years, 74.1% female, 64.7% biologics-naïve), 106 had psoriatic arthritis (PsA) (48.1 years, 70% female, 66.0% biologics-naïve) and 478 had axial spondyloarthritis (axSpA) (42.8 years, 54.6% female, 60.9% biologics-naïve). Golimumab persistence at 2 years was 56.5%, 45.1% and 52.6%, respectively, in RA, PsA and axSpA groups. Persistence was higher in biologics-naïve (58.3%) than in biologics pre-treated patients (42.7%, p<0.01). For 362 patients continuing golimumab at 2 years, disease activity improved significantly from baseline to 2 years: mean 28-joint disease activity score for RA and PsA was lowered by 2.06 and 1.89 points, and mean ankylosing spondylitis disease activity score was lowered by 3.11 points (p<0.0001) for axSpA. Patient appreciation of disease activity also improved; 8.9% of discontinuations were due to intolerance. CONCLUSIONS: Golimumab persistence was satisfactory at 2 years and accompanied by improvements in clinical effectiveness in 362 patients continuing golimumab at 2 years. Golimumab was well tolerated and its safety profile was consistent with those reported in previous studies.

Complete Genome Sequence of Microbacterium sp. Strain Nx66, Isolated from Waters Contaminated with Petrochemicals in El Saf-Saf Valley, Algeria.

Microbacterium sp. strain Nx66 was isolated from waters contaminated by petrochemical effluents collected in Algeria. Its genome was sequenced using Illumina MiSeq (2 × 150-bp read pairs) and Oxford Nanopore (long reads) technologies and was assembled using Unicycler. It is composed of one chromosome of 3.42 Mb and one plasmid of 34.22 kb.

Part of pain labelled neuropathic in rheumatic disease might be rather nociplastic.

Pain in rheumatic diseases is primarily due to mechanical or inflammatory mechanism, but neuropathic pain (NP) component is also occurring in many conditions and is probably underdiagnosed. The purpose of this article is to provide an overview of prevalence, pathophysiological and currently available treatment of NP in rheumatic diseases. When associated with clinical evaluation assessing neurological clinical signs and neuroanatomical distribution, Douleur Neuropathique 4 Questions, painDETECT, Leeds assessment of neuropathic symptoms and signs and Neuropathic Pain Questionnaire can detect NP component. Inflammatory or connective diseases, osteoarthritis, back pain or persistent pain after surgery are aetiologies that all may have a neuropathic component. Unlike nociceptive pain, NP does not respond to usual analgesics such as paracetamol and non-steroidal anti-inflammatory drugs. Entrapment neuropathy, peripheral neuropathy or small-fibre neuropathy are different aetiologies that can lead to NP. A part of the pain labelled neuropathic is rather nociplastic, secondary to a central sensitisation mechanism. Identifying the right component of pain (nociceptive vs neuropathic or nociplastic) could help to better manage pain in rheumatic diseases with pharmacological and non-pharmacological treatments.

Visit-to-Visit Blood Pressure Variability Is Associated With Cognitive Decline and Incident Dementia: The S.AGES Cohort.

To investigate the impact of visit-to-visit systolic blood pressure variability (BPV), diastolic BPV, mean arterial pressure variability, and pulse pressure variability on cognitive decline and incident dementia in noninstitutionalized patients aged ≥65 years. A total of 3319 subjects from the S.AGES (Sujets AGÉS-Aged Subjects) cohort underwent clinical examinations every 6 months during 3 years. Variability was evaluated using standard deviation (SD), coefficient of variation, average real variability, successive variation, variation independent of mean, and residual SD. Cognition was assessed using the Mini-Mental State Examination and dementia with the Diagnostic Statistical Manual of Mental Disorders. Linear mixed models and Cox proportional hazards models were used. Higher systolic BPV was associated with poorer cognition independently of baseline SBP: adjusted 1-SD increase of coefficient of variation: ß (SE)=-0.12 (0.06), P=0.04. Similar results were observed for diastolic BPV and mean arterial pressure variability: ß (SE)=-0.20 (0.06), P<0.001 for both. Higher pulse pressure variability was no longer associated with cognitive function after adjustment for age, except with residual SD (P=0.02). Among the 3319 subjects, 93 (2.8%) developed dementia. Higher systolic BPV was associated with greater dementia risk (adjusted 1-SD increase of coefficient of variation: hazard ratios=1.23 [95% CI, 1.01-1.50], P=0.04). Similar results were found for diastolic BPV and mean arterial pressure variability (P<0.01). Pulse pressure variability was not associated with dementia risk. Beyond hypertension, higher BPV is a major clinical predictor of cognitive impairment and dementia. Further studies are needed to assess whether controlling BP instability could be a promising interventional target in preserving cognition among older adults.

The burden of pain in rheumatoid arthritis: Impact of disease activity and psychological factors.

BACKGROUND: Pain remains a prevalent symptom for rheumatoid arthritis (RA) patients despite a wide therapeutic choice. The objective of this study was to provide a multidimensional evaluation of pain. METHODS: A total of 295 RA patients from 7 French rheumatology centres were enrolled in a cross-sectional study. Patients completed a chronic pain assessment questionnaire approved by the French National Authority for Health, the health assessment questionnaire (HAQ) as well as depression and anxiety scales (HAD, Beck Depression Inventory, STAI). Disease activity (DAS28) and ESR were recorded. A multivariate descriptive analysis was undertaken using principal component analysis (PCA). RESULTS: 38.4% of patients had a pain score > 40 mm/100, although 83% were on biological treatment and 38.7% were in remission based on the RA activity score. The PCA analysis found four axes representing 70% of total variance. The axes, per cent of variance and variables represented were as follows: (a) axis 1, 41% variance, anxiety and depression scores, sensory and affective qualifier score, HAQ and pain impact on daily life; (b) axis 2, 13% variance, disease activity score (DAS28) and pain relief with current treatment; (c) axis 3, 9% of variance, RA duration and radiographic score and (d) axis 4, 6% of variance, DAS28 and ESR. Moderate to severe pain was significantly associated with axes 1 and 2. CONCLUSIONS: Despite a high proportion of patients on biological treatments, 38.4% of patients continue to experience moderate to severe pain. Pain is associated with the RA activity score, but also with the depression and anxiety scores. SIGNIFICANCE: Substantial proportion of rheumatoid arthritis (RA) patients still experiences relevant pain, although more than 80% on biological treatment. Pain is primarily associated with anxiety and depression scores and with disease activity score. These findings highlight the need to assess patients' mental well-being alongside. Clinical measures of disease activity to better manage pain and guide treatment decisions.

Sex Differences in the Occurrence of Major Clinical Events in Elderly People with Type 2 Diabetes Mellitus Followed up in the General Practice.

AIMS: The main aim of the present work was to assess if sex influences the occurrence of major clinical events in elderly people with type 2 diabetes followed up in the primary care. METHODS: 983 subjects aged ≥65years with type 2 diabetes were included by 213 general practitioners and followed up prospectively for three years. Major clinical events were recorded every six month. The first endpoint was a composite of all-cause death and major vascular events (acute coronary syndrome, non-fatal stroke or transient ischemic attack, or revascularization for peripheral artery disease). The second endpoint was all-cause hospitalization. The occurrence of each endpoint was analyzed in order to estimate the role of sex and determine other predictors of major clinical events. RESULTS: At baseline, women were older than men but they had a lower prevalence of coexisting diseases (cardiovascular disease and cancer) and equivalent diabetes control (Glycated hemoglobin A1C: 6.9%±0.9 vs. 7.0%±1.1). Over the follow-up period, women were at lower risk to develop the composite endpoint (HR 0.60, 95% CI 0.40-0.91, p=0.016) and the hospitalization endpoint (OR 0.71, 95% CI 0.52-0.96, p=0.029). Coexisting diseases, functional ability and concomitant medications emerged as significant predictors of both endpoints. CONCLUSIONS: Elderly women with well-controlled type 2 diabetes were less likely to experience major clinical events than their male counterparts. More studies are needed to determine the reasons for the higher hospitalization rate in men.

In situ metabolic activities of uncultivated Ferrovum sp. CARN8 evidenced by metatranscriptomic analysis.

Amongst iron-oxidizing bacteria playing a key role in the natural attenuation of arsenic in acid mine drainages (AMDs), members of the Ferrovum genus were identified in mine effluent or water treatment plants, and were shown to dominate biogenic precipitates in field pilot experiments. In order to address the question of the in situ activity of the uncultivated Ferrovum sp. CARN8 strain in the Carnoulès AMD, we assembled its genome using metagenomic and metatranscriptomic sequences and we determined standardized expression values for protein-encoding genes. Our results showed that this microorganism was indeed metabolically active and allowed us to sketch out its metabolic activity in its natural environment. Expression of genes related to the respiratory chain and carbon fixation suggests aerobic energy production coupled to ferrous iron oxidation and chemolithoautotrophic growth. Notwithstanding the presence of nitrogenase genes in its genome, expression data also indicated that Ferrovum sp. CARN8 relied on ammonium import rather than nitrogen fixation. The expression of flagellum and chemotaxis genes hints that at least a proportion of this strain population was motile. Finally, apart from some genes related to metal resistance showing surprisingly low expression values, genes involved in stress response were well expressed as expected in AMDs.

Multicenter, Prospective, Controlled Double-Blind Study Comparing Fib-19-01, A Phytotherapy Treatment, To A Dietary Supplement And To Conventional Care In Patients Suffering From Fibromyalgia.

BACKGROUND: Current therapeutic modalities for fibromyalgia (FM) do not provide satisfactory results and new approaches have to be explored. OBJECTIVES: To assess efficacy and safety of adding a phytotherapy treatment (Fib-19-01) to the current therapeutic regimen in patients with FM. METHODS: Double-blind controlled trial: women with active FM (Fibromyalgia Index Questionnaire FIQ > 40) were randomised to receive Fib-19-01 or a food supplement (FS) undistinguishable from Fib-19-01 or no supplementary treatment (NoST). All continued the conventional therapy throughout the 6 month follow-up. Primary endpoint: change in FIQ between Day 0 and month 6 (M6). Secondary Criteria: variation over time FIQ ( repeated measurements), change in Pichot fatigue scale, Pittsburgh Sleep Quality Index (PSQI), SF-12 and Hospital Anxiety and Depression (HAD) scales. RESULTS: 100 patients (Intent-To-Treat population) were analyzed. FIQ decreased significantly only in the Fib-19-01 group (P < .001) at both week 12 and 24. Improvement was higher for Fib-19-01 (-13.4 ± 18.9) than in the 2 other groups (-5.5 ± 15.6 and -5.6 ± 11.3) despite there was no statistical between-group difference at week 24 in FIQ score (P = .08 and P = .09 respectively). Analysis of variance in repeated measurements of FIQ showed a significant difference between Fib-19-01 and FS throughout the follow-up period (P = .03). Fib-19-01 was superior to both FS and NoST for Pichot scale decrease over time: -4.6 (range -6.9; -2.28), -0.29 (-2.7; 2.1) and -0.72 (-3.1; 1.66) (P = .013 and 0.023 respectively), mental and social SF12 [+8.1 (range 3.5; 12.6), -0.27(range -5.3; 4.8 ) and -0.02 (range -5.0; 4.9 ) P = .02 and 0.018)],HAD depression [-2.0 (range -3.3; -0.7), +0.5 (range -0.9; 1.9 ) and +0.71 (range -0.7; 2.1) P = .013 and 0.007]. No significant difference was found between FS and NoST groups for any outcome. All treatments were well and similarly tolerated. CONCLUSIONS: In patients with FM taking conventional therapy, Fib-19-01 has a therapeutic effect on fatigue, emotion and social life, and depression associated with the disease.