Characteristics of refractory disease and persistent symptoms in inflammatory arthritis:Qualitative framework analysis of interviews with patients and health care professionals

OBJECTIVES: This study aims to explore patients' and clinicians' understanding and experiences of refractory disease (RD) and persistent physical and emotional symptoms (PPES) in patients with inflammatory arthritis (IA), namely rheumatoid arthritis or polyarticular juvenile idiopathic arthritis from their perspectives through interviews and/or focus groups.DESIGN: A qualitative study was conducted, following a pragmatic epistemology approach with framework analysis employed.METHODS: Semi-structured interviews or focus groups with IA patients (n = 25) and multi-disciplinary rheumatology HCPs (n = 32) were conducted at one time point to obtain participants respective understanding and experiences of managing RD/PPES, and its impact on the patient-professional relationship.RESULTS: Three key themes were identified from both patients and professionals' experiences of RD/PPES: (1) relevant treatment experiences, (2) symptoms (with or without inflammation) and (3) impact: physical, psychological and social. These themes included 28 specific categories that would be considered as components characterizing RD/PPES, most common to both patients and HCPs with six being patient-specific and only one HCP-specific. The specific biopsychosocial symptoms and impacts of RD/PPES pertain to pain, fatigue, stiffness, joint involvement and physical, psychological and social functioning and quality of life, covering disease-related distress, mobility and independence. Wider influential factors such as comorbidities, non-adherence, health/medication beliefs and behaviours and social support were also identified.CONCLUSION: Common persistent symptoms that have both mental and physical impact characterize RD/PPES in IA and therefore a more integrated holistic approach to treatment is needed from multi-disciplinary HCPs, including health psychologists.</p

Detection of Head-to-Tail DNA Sequences of Human Bocavirus in Clinical Samples

Parvoviruses are single stranded DNA viruses that replicate in a so called “rolling-hairpin” mechanism, a variant of the rolling circle replication known for bacteriophages like ϕX174. The replication intermediates of parvoviruses thus are concatemers of head-to-head or tail-to-tail structure. Surprisingly, in case of the novel human bocavirus, neither head-to-head nor tail-to-tail DNA sequences were detected in clinical isolates; in contrast head-to-tail DNA sequences were identified by PCR and sequencing. Thereby, the head-to-tail sequences were linked by a novel sequence of 54 bp of which 20 bp also occur as conserved structures of the palindromic ends of parvovirus MVC which in turn is a close relative to human bocavirus

Characteristics of refractory disease and persistent symptoms in inflammatory arthritis: Qualitative framework analysis of interviews with patients and health care professionals

ObjectivesThis study aims to explore patients' and clinicians' understanding and experiences of refractory disease (RD) and persistent physical and emotional symptoms (PPES) in patients with inflammatory arthritis (IA), namely rheumatoid arthritis or polyarticular juvenile idiopathic arthritis from their perspectives through interviews and/or focus groups.DesignA qualitative study was conducted, following a pragmatic epistemology approach with framework analysis employed.MethodsSemi-structured interviews or focus groups with IA patients (n = 25) and multi-disciplinary rheumatology HCPs (n = 32) were conducted at one time point to obtain participants respective understanding and experiences of managing RD/PPES, and its impact on the patient-professional relationship.ResultsThree key themes were identified from both patients and professionals' experiences of RD/PPES: (1) relevant treatment experiences, (2) symptoms (with or without inflammation) and (3) impact: physical, psychological and social. These themes included 28 specific categories that would be considered as components characterizing RD/PPES, most common to both patients and HCPs with six being patient-specific and only one HCP-specific. The specific biopsychosocial symptoms and impacts of RD/PPES pertain to pain, fatigue, stiffness, joint involvement and physical, psychological and social functioning and quality of life, covering disease-related distress, mobility and independence. Wider influential factors such as comorbidities, non-adherence, health/medication beliefs and behaviours and social support were also identified.ConclusionCommon persistent symptoms that have both mental and physical impact characterize RD/PPES in IA and therefore a more integrated holistic approach to treatment is needed from multi-disciplinary HCPs, including health psychologists

COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study.

BACKGROUND: A subset of patients with severe COVID-19 develop a hyperinflammatory syndrome, which might contribute to morbidity and mortality. This study explores a specific phenotype of COVID-19-associated hyperinflammation (COV-HI), and its associations with escalation of respiratory support and survival. METHODS: In this retrospective cohort study, we enrolled consecutive inpatients (aged ≥18 years) admitted to University College London Hospitals and Newcastle upon Tyne Hospitals in the UK with PCR-confirmed COVID-19 during the first wave of community-acquired infection. Demographic data, laboratory tests, and clinical status were recorded from the day of admission until death or discharge, with a minimum follow-up time of 28 days. We defined COV-HI as a C-reactive protein concentration greater than 150 mg/L or doubling within 24 h from greater than 50 mg/L, or a ferritin concentration greater than 1500 μg/L. Respiratory support was categorised as oxygen only, non-invasive ventilation, and intubation. Initial and repeated measures of hyperinflammation were evaluated in relation to the next-day risk of death or need for escalation of respiratory support (as a combined endpoint), using a multi-level logistic regression model. FINDINGS: We included 269 patients admitted to one of the study hospitals between March 1 and March 31, 2020, among whom 178 (66%) were eligible for escalation of respiratory support and 91 (34%) patients were not eligible. Of the whole cohort, 90 (33%) patients met the COV-HI criteria at admission. Despite having a younger median age and lower median Charlson Comorbidity Index scores, a higher proportion of patients with COV-HI on admission died during follow-up (36 [40%] of 90 patients) compared with the patients without COV-HI on admission (46 [26%] of 179). Among the 178 patients who were eligible for full respiratory support, 65 (37%) met the definition for COV-HI at admission, and 67 (74%) of the 90 patients whose respiratory care was escalated met the criteria by the day of escalation. Meeting the COV-HI criteria was significantly associated with the risk of next-day escalation of respiratory support or death (hazard ratio 2·24 [95% CI 1·62-2·87]) after adjustment for age, sex, and comorbidity. INTERPRETATION: Associations between elevated inflammatory markers, escalation of respiratory support, and survival in people with COVID-19 indicate the existence of a high-risk inflammatory phenotype. COV-HI might be useful to stratify patient groups in trial design. FUNDING: None

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Algorithms to estimate Antarctic sea ice algal biomass from under-ice irradiance spectra at regional scales

The presence of algal pigments in sea ice alters under-ice irradiance spectra, and the relationship between these variables can be used as a non-invasive means for estimating ice- associated algal biomass on ecologically relevant spatial and temporal scales. While the influence of snow cover and ice algal biomass on spectra transmitted through the snow-ice matrix has been examined for the Arctic, it has not been tested for Antarctic sea ice at regional scales. We used paired measurements of sea ice core chla concentrations and hyperspectral-transmitted under-ice irradiances from 59 sites sampled off East Antarctica and in the Weddell Sea to develop algorithms for estimating algal biomass in Antarctic pack ice. We compared 4 approaches that have been used in various bio-optical studies for marine systems: normalised difference indices, ratios of spectral irradiance, scaled band area and empirical orthogonal functions. The percentage of vari- ance explained by these models ranged from 38 to 79%, with the best-performing approach being normalised difference indices. Given the low concentrations of integrated chl a observed in our study compared with previous studies, our statistical models performed surprisingly well in explaining variability in these concentrations. Our findings provide a basis for future work to develop methods for non-invasive time series measurements and medium- to large-scale spatial mapping of Antarctic ice algal biomass using instrumented underwater vehicles

Haemophagocytic lymphohisticytosis—an underrecognized hyperinflammatory syndrome

AbstractHaemophagocytic lymphohisticytosis (HLH) is a syndrome of uncontrolled, severe systemic inflammation (hyperinflammation) arising either from a genetic immune system defect [primary (pHLH)] or triggered as a complication of malignancy, infection, or rheumatologic disease [secondary (sHLH)]. Patients with HLH often have non-specific symptoms and become progressively and critically unwell, with fever, cytopenia and multi-organ failure. Untreated, HLH is almost universally fatal, but even when treated, mortality is high, particularly when HLH complicates malignancy. HLH is managed with immunosuppression, and this can seem difficult to justify in such unwell patients. This review aims to examine the diagnostic and treatment challenges posed by sHLH and to improve recognition among rheumatologists who, being expert in the management of multisystem diseases and in the use of immunosuppression, are ideally placed to deliver care and build an evidence base for better disease characterization and treatment.</jats:p