Clinical trajectories of hand function impairment in systemic sclerosis: an unmet clinical need across disease subsets.

BACKGROUND: Hand involvement is an early manifestation of systemic sclerosis (SSc), culprit of diagnosis and classification, and recognised major driver of disability. Impairment of hand function burdens both limited and diffuse cutaneous subsets and therefore could be targeted as 'basket' endpoint in SSc. Nevertheless, its natural history in current standard of care is not well characterised, limiting the design of targeted trials. The aim of this study is to describe prevalence, natural history and clinical factors associated with hand function deterioration in a longitudinal, multicentre, observational SSc cohort. METHODS: Hand function was captured through the validated Cochin Hand Function Scale in patients consecutively enrolled in a multicentre observational study and observed over 24 months. Minimal clinically important differences and patient acceptable symptom state were analysed as previously described. RESULTS: Three hundred and ninety-six consecutive patients were enrolled from 10 centres; 201 with complete follow-up data were included in the analysis. Median (IQR) disease duration was 5 (2-11) years. One hundred and five (52.2%) patients reported clinically significant worsening. Accordingly, the proportion of patients reporting unacceptable hand function increased over 2 years from 27.8% to 35.8% (p<0.001). Least absolute shrinkage and selection operator analysis identified male gender, disease subset, Raynaud's Condition Score, tenosynovitis and pain, as some of the key factors associated with worsening hand involvement. CONCLUSIONS: Hand function deteriorates over time in more than 50% of SSc patients despite available therapies. The analysis of factors associated with hand function worsening supports the involvement of both inflammation, vascular and fibrotic processes in hand involvement, making it a hallmark clinical manifestation of SSc. Our data are poised to inform the design of intervention studies to target this major driver of disability in SSc.

Toxic leadership behaviour of nurse managers and turnover intentions: the mediating role of job satisfaction.

INTRODUCTION: Globally, hospitals are confronted with major challenges of turnover of nurses. Knowledge of the factors that account for the turnover of nurses will aid in creating strategies that will enhance nurse managers' leadership behaviour and job satisfaction to reduce turnover. The study, therefore, investigated the mediating role of job satisfaction on toxic leadership and turnover intentions of nurses. METHODS: A multi-centre cross-sectional study was undertaken to assess 943 nurses using the Toxic-leadership Behaviour of Nurse Managers scale, Minnesota Satisfaction Questionnaire and Turnover Intention scale. Descriptive statistics was used to assess the prevalence of toxic leadership, job satisfaction and turnover and Pearson's correlation examined the relationships between the variables. Hayes' PROCESS macro approach of mediation was used to determine the effect of toxic leadership behaviour on the turnover intention on the possible influence of job satisfaction. RESULTS: The response rate for the study was 76.0%. Mean scores for turnover intentions and toxic leadership behaviour were 3.71 and 2.42 respectively. Nurses who work with toxic managers showed a higher propensity to leave their jobs. Job satisfaction acted as a mediator between the toxic leadership practices of managers and turnover intentions. The total effect of toxic leadership behaviour on turnover intention comprised its direct effect (ß = 0.238, SE = 0.017, 95% CI [0.205, 0.271]) and its indirect effect (ß = -0.020, SE = 0.017). CONCLUSIONS: Job satisfaction acted as a mediating factor for toxic leadership behaviour and nurses' turnover intentions. As part of nurse retention initiatives, avoiding toxic leadership behaviours will be the ultimate agenda. Nurse administrators should recognize the value of excellent leadership and develop a structured training programme through the use of evidence-based professional development plans for nurse managers.

Toxic leadership behaviour of nurse managers on perceived job satisfaction and productivity of nursing workforce in sub-Saharan Ghana: A multi-centre cross-sectional study.

AIM: This study aimed at assessing the nature and effect of toxic leadership of nurse managers on the perceived job satisfaction and productivity of the nursing workforce. BACKGROUND: Nursing job outcomes such as job satisfaction and productivity are influenced by various factors in the nursing practice environment including leadership. Due to rising health care expenses and depleting material resources, the productivity of nurses that is expected to improve the efficiency of health care organizations is mostly low. Managers' toxic behaviour towards nurses affects their job satisfaction and subsequently low productivity. METHOD: A multi-centre, cross-sectional descriptive design was used. Validated tools were used to collect data from participants, and data were analysed using descriptive, correlation, and hierarchical linear regressions. RESULTS: Registered nurses appraised the leadership behaviour of nurse managers to be toxic, with most managers exhibiting narcissistic leadership behaviour. Though all the components of toxic leadership behaviour of manager and job satisfaction were associated with the perceived productivity of the nurses; only intemperate leadership behaviour of the managers (ß = -.301, p < .005), and job satisfaction (ß = .296, p < .001) significantly predicted perceived productivity among nurses (R2 = .238, F(7, 922) = 41.088, p < .001). CONCLUSION: Nurse managers' leadership behaviours were toxic. Nurses' job satisfaction and all components of managers' toxic leadership behaviour influenced productivity. IMPLICATIONS FOR NURSING MANAGEMENT: There should be a policy developed to guide the creation and maintenance of efficient nursing leadership to enhance job satisfaction and productivity among nurses.

Exploring the planning practices of nurse managers in the unit: a study of nurse managers in the greater Accra region.

PURPOSE: Nurse managers' planning practices are essential to the practice of management in the unit, and the overall efficiency of the healthcare service delivery. This study aims to explore the planning practices of nurse managers in the Greater Accra Region, Ghana. DESIGN/METHODOLOGY/APPROACH: A descriptive phenomenological design was employed to explore nurse managers' planning practices. In total, 15 nurse managers and 47 nurses from 19 primary and secondary hospitals of the Ghana Health Service and two specialized hospitals in the Greater Accra Region, Ghana, were involved in the study. Data were collected using semi-structured interview guides and probes. FINDINGS: The findings suggested that plans were widely common to all the units of the hospitals and were considered satisfactory by nurse managers. However, most of these plans were not effectively utilized. Nurse managers had only fair knowledge about the planning process and were moderately involved and communicated ideas to colleagues in the process. Furthermore, nurse managers do not frequently share the vision neither do they even communicate expectations to achieve unit goals and objectives with subordinates. ORIGINALITY/VALUE: The research emphasizes the relevance of planning in healthcare management. It highlights the management practice of planning in the context of nurse managers and accentuates the values the healthcare system derives with effective planning practices.

Staffing the unit with nurses: the role of nurse managers.

PURPOSE: To explore the staffing practices of nurse managers at the unit. DESIGN/METHODOLOGY/APPROACH: Introduction: Ensuring that units are staffed with adequate nurses to render quality nursing care to clients has become increasingly challenging for most hospitals. There is growing evidence linking best patient outcomes and fewer adverse events to the presence of nurses at the bedside. Hospitals require to attract and retain nurses in the units to address the issues of quality, staff and patient safety. Methods: The study used a descriptive phenomenological design to purposively select 15 nurse managers (NMs) and 47 nurses for in-depth interviews and focus group discussions respectively. FINDINGS: The study found that the demand for nurses to work in the unit was not scientific. Nurses affirmed their frustration of inadequate numbers of staff in the unit especially, at the periphery hospitals. Time can be used as a source of motivation for nurses and nurses should be involved in the development of the duty roster to enable effective compliance. Compensation for additional duties is relevant in nursing. RESEARCH LIMITATIONS/IMPLICATIONS: The research was carried only in one region in Ghana, and the findings may not be the same in the other regions. PRACTICAL IMPLICATIONS: Inadequate staffing level has serious implications on patient safety, quality of care and staff outcomes. This situation necessitates the implementation of health sector staffing norms to ensure the right calibre of mix staff are recruited and retained. ORIGINALITY/VALUE: This study is the first in Ghana that we aware of that explore staffing practices at the unit that identifies factors that impact staff schedules for effective care.

Vasoplegia after cardiopulmonary bypass: A narrative review of pathophysiology and emerging targeted therapies.

Cardiovascular disease remains the leading cause of death in the United States, and cardiopulmonary bypass is a cornerstone in the surgical management of many related disease states. Pathophysiologic changes associated both with extracorporeal circulation and shock can beget a syndrome of low systemic vascular resistance paired with relatively preserved cardiac output, termed vasoplegia. While increased vasopressor requirements accompany vasoplegia, related pathophysiologic mechanisms may also lead to true catecholamine resistance, which is associated with further heightened mortality. The introduction of a second non-catecholamine vasopressor, angiotensin II, and non-specific nitric oxide scavengers offers potential means by which to manage this challenging phenomenon. This narrative review addresses both the definition, risk factors, and pathophysiology of vasoplegia and potential therapeutic interventions.

Acute Postoperative Pain Is Associated With Myocardial Injury After Noncardiac Surgery.

BACKGROUND: Uncontrolled pain after noncardiac surgery activates the sympathetic nervous system, which causes tachycardia, hypertension, and increased cardiac contractility-all of which may increase myocardial oxygen demand. We therefore determined whether time-weighted average pain scores over the initial 72 postoperative hours are associated with myocardial injury after noncardiac surgery (MINS). METHODS: We conducted a retrospective cohort analysis of adults with routine postoperative troponin monitoring after noncardiac surgery under general, regional, or combined anesthesia at tertiary level centers in Cleveland from January 2012 to December 2015. Time-weighted average pain scores were calculated from all the available pain scores, typically at 4-hour intervals, until a troponin elevation was detected. MINS was defined as peak troponin T concentrations exceeding 0.03 ng/mL within 72 hours after surgery. We used a generalized linear mixed model to assess the association between pain and MINS with 3 hospitals as clusters, adjusting for potential confounders. RESULTS: Among 2892 eligible patients, 4.5% had myocardial injury within 72 hours after surgery. Higher time-weighted average pain scores were associated with increased hazard of myocardial injury. The estimated hazard ratio for a 1-unit increase in pain score was 1.12 (95% confidence interval [CI], 1.02-1.22; P = .013), adjusting for confounding variables. CONCLUSIONS: Among patients undergoing noncardiac surgery, time-weighted average pain scores within 72 hours after surgery were significantly associated with myocardial injury.

Correction to: Biologic monotherapy in the biologic naïve patient with rheumatoid arthritis (RA): results from an observational study.

In the original article, the corresponding author's given name and middle name were interchanged.

Biologic monotherapy in the biologic naïve patient with rheumatoid arthritis (RA): results from an observational study.

Approximately one-third of patients on biologic therapy for rheumatoid arthritis (RA) receive them as monotherapy. There are few head-to-head randomised control trials comparing biologics as monotherapy. Our aim was to compare the efficacy and persistence of multimodal biologic agents as monotherapy in biologic naïve patients with RA in the real-world setting. A multicentre retrospective observational study was carried out comparing TNF inhibitors (TNFi), IL6 receptor inhibitor (IL6Ri) and CTLA-4 inhibitor (CTLA-4i) monotherapy in biologic naïve RA patients. The primary study outcome was DAS28 score at 6, 12, and 18 months. 126 patients were enrolled; 98 patients (78%) were taking TNFi, 19 patients (15%) IL6Ri and 10 (8%) CTLA-4i with similar baseline characteristics of sex and age across groups. Patients in the CTLA-4i group were more often seropositive and had greater numbers of comorbidities. At 6 and 12 months, patients in the IL6Ri group had a lower DAS28 score compared to TNFi monotherapy. Those on CTLA-4i monotherapy also had a lower DAS28 score at 6 months than the TNFi group, although differences were lost by 12 months. Drug retention at 18 months was highest in the IL6Ri arm (68%) and CTLA-4i arm (80%) compared with only 55% in the TNFi group. Our findings support current guidance that IL6Ri should be considered in biologic naïve patients requiring biologic monotherapy, but also indicated that CTLA-4i could be an option.

Sepsis information-seeking behaviors via Wikipedia between 2015 and 2018: A mixed methods retrospective observational study.

Raising public awareness of sepsis, a potentially life-threatening dysregulated host response to infection, to hasten its recognition has become a major focus of physicians, investigators, and both non-governmental and governmental agencies. While the internet is a common means by which to seek out healthcare information, little is understood about patterns and drivers of these behaviors. We sought to examine traffic to Wikipedia, a popular and publicly available online encyclopedia, to better understand how, when, and why users access information about sepsis. Utilizing pageview traffic data for all available language localizations of the sepsis and septic shock pages between July 1, 2015 and June 30, 2018, significantly outlying daily pageview totals were identified using a seasonal hybrid extreme studentized deviate approach. Consecutive outlying days were aggregated, and a qualitative analysis was undertaken of print and online news media coverage to identify potential correlates. Traffic patterns were further characterized using paired referrer to resource (i.e. clickstream) data, which were available for a temporal subset of the pageviews. Of the 20,557,055 pageviews across 65 linguistic localizations, 47 of the 1,096 total daily pageview counts were identified as upward outliers. After aggregating sequential outlying days, 25 epochs were examined. Qualitative analysis identified at least one major news media correlate for each, which were typically related to high-profile deaths from sepsis and, less commonly, awareness promotion efforts. Clickstream analysis suggests that most sepsis and septic shock Wikipedia pageviews originate from external referrals, namely search engines. Owing to its granular and publicly available traffic data, Wikipedia holds promise as a means by which to better understand global drivers of online sepsis information seeking. Further characterization of user engagement with this information may help to elucidate means by which to optimize the visibility, content, and delivery of awareness promotion efforts.

The supra-iliac anterior quadratus lumborum block: a cadaveric study and case series.

PURPOSE: The local anesthetic injectate spread with fascial plane blocks and corresponding clinical outcomes may vary depending on the site of injection. We developed and evaluated a supra-iliac approach to the anterior quadratus lumborum (QL) block and hypothesized that this single injection might successfully block the lumbar and sacral plexus in cadavers and provide analgesia for patients undergoing hip surgery. METHODS: Ultrasound-guided bilateral supra-iliac anterior QL blocks were performed with 30 mL of India ink dye in six fresh adult cadavers. Cadavers were subsequently dissected to determine distribution of the dye. In five patients undergoing hip surgery, a unilateral supra-iliac anterior QL block with 25 mL ropivacaine 0.5% followed by a continuous catheter infusion was performed. Patients were clinically assessed daily for block efficacy. RESULTS: The cadaveric injections showed consistent dye involvement of the majority of the branches of the lumbar plexus, including the femoral nerve, lateral femoral cutaneous nerve, ilioinguinal nerve, and iliohypogastric nerve. The majority of cadaveric specimens (83%) also exhibited thoracic paravertebral spread of dye to the T10 level. No specimens showed L5 or sacral nerve root staining or caudal spread below L5. All patients had effective analgesia for total hip surgery and a T11-L3 sensory level following the initial bolus of local anesthetic as well as during the period of continuous catheter infusion. CONCLUSION: This cadaveric study and case series show that a supra-iliac approach to the anterior QL block involved T10--L3 nerve territories and dermatomal coverage with no sacral plexus spread. This technique may have clinical utility for analgesia in hip surgery.

RéSUMé: OBJECTIF: La diffusion de l'anesthésique local injecté lors de la réalisation d'un bloc du fascia et les résultats cliniques qui en découlent peuvent varier selon le site d'injection. Nous avons mis au point et évalué une approche supra-iliaque pour la réalisation d'un bloc du muscle carré des lombes antérieur (quadratus lomburum) et émis l'hypothèse que cette injection unique pourrait suffire à bloquer les plexus lombaire et sacral de cadavres, offrant ainsi une analgésie aux patients subissant une chirurgie de la hanche. MéTHODE: Des blocs bilatéraux du muscle carré des lombes antérieur ont été réalisés par approche supra-iliaque sous échoguidage à l'aide de 30 mL de teinture d'encre de Chine sur six cadavres adultes frais. Les cadavres ont par la suite été disséqués afin de déterminer la diffusion de la teinture. Nous avons réalisé un bloc unilatéral du muscle carré des lombes antérieur par approche supra-iliaque avec une solution de 25 mL de ropivacaïne 0,5 %, suivie d'une perfusion continue via cathéter, chez cinq patients subissant une chirurgie de la hanche. Une évaluation clinique quotidienne des patients a été réalisée afin de déterminer l'efficacité du bloc. RéSULTATS: Les injections sur les cadavres ont permis d'observer une diffusion constante de la teinture dans la majorité des branches du plexus lombaire, y compris dans le nerf fémoral, le nerf fémoral cutané latéral, le nerf ilio-inguinal et le nerf ilio-hypogastrique. Une diffusion paravertébrale thoracique de la teinture jusqu'au niveau T10 a également été retrouvée dans la majorité des spécimens cadavériques (83 %). Aucune coloration au niveau de la racine L5 ou des nerfs sacrés n'a été observée chez les spécimens, ni aucune diffusion caudale au-dessous de L5. Tous les patients ont reçu une analgésie efficace pour une arthroplastie totale de la hanche et obtenu un bloc sensitif au niveau T11­L3 après l'injection du bolus initial d'anesthésique local ainsi qu'au cours de la période de perfusion continue. CONCLUSION: Cette étude cadavérique et cette série de cas montrent qu'une approche supra-iliaque pour réaliser un bloc du muscle du carré des lombes antérieur est parvenue à atteindre les territoires nerveux T10-­L3 et avec couverture de ces dermatomes et ce, sans diffusion au niveau du plexus sacré. Cette technique pourrait avoir une utilité clinique pour l'analgésie en cas de chirurgie de la hanche.

Preliminary experience with epidural and perineural catheter localization with pulsed wave Doppler ultrasonography.

BACKGROUND: Various methods for peripheral nerve and epidural catheter location assessment exist, with varying degrees of ease of use, utility, and accuracy. Pulsed wave Doppler (PWD) evaluates the presence of fluid flow and is possible modality to assess the location of a percutaneously inserted perineural catheter. METHODS: A retrospective chart review was conducted in which PWD ultrasonography was used to confirm the position of nerve catheters for regional anesthesia. Data was collected to assess 24-hour postoperative pain scores, opioid consumption, complications, and the incidence of catheter replacement. RESULTS: Eighty-six patients were included; average age was 58 years and a 27% incidence of chronic pain. These catheters were left in place based on the PWD images. Three catheters failed and a total of 16 catheters were repositioned. In the first 24 hours average pain scores ranges between 3.5 to 5.9 and median postoperative opioid consumption range was 11.3 mg to 60.8 mg. For epidural catheters, PWD changes were more obvious with air injection and there was only one episode of hemodynamic instability. CONCLUSIONS: Our preliminary experience with PWD ultrasonography suggests that they may offer the ability to selectively assess flow at different locations to identify the proper location of epidural and perineural catheters. Future randomized, controlled investigations are warranted to further evaluate the effectiveness and safety of this modality.

Baseline vWF factor predicts the development of elevated pulmonary artery pressure in systemic sclerosis.

OBJECTIVES: This study aims to examine the utility of von Willebrand factor (vWF) as a biomarker in lcSSc, in particular the ability of vWF to predict the future development of disease manifestations in this disease. METHODS: vWFAg concentrations were measured in the serum of patients with lcSSc at baseline and at 3 years, during the QUINs trial [Prevention of Vascular Damage in Scleroderma with Angiotensin-Converting Enzyme (ACE) Inhibition]. %DL(CO), %KCO, %FVC, pulmonary artery pressure (PAP) estimation by echocardiography, Raynaud's attack frequency, Raynaud's severity, digital ulcer frequency, urinary protein excretion, estimated glomerular filtration rate (eGFR), modified Rodnan skin score and Medsger disease activity score were also measured at baseline and 3 years. RESULTS: Baseline serum vWF concentrations were related to concurrent Medsger disease activity score, %DL(CO), %FVC, urinary protein excretion, eGFR and PAP >30 mmHg. In logistic regression models, baseline serum vWF concentrations were able to predict the future development of elevated PAP by echocardiography (PAP >40 mmHg, P = 0.001). CONCLUSIONS: Pulmonary artery hypertension is a life-threatening complication of lcSSc. vWF is a marker of endothelial cell activation. Raised serum concentrations of vWF in lcSSc increase the risk of developing subsequent elevation in PAP. Therefore screening patients with lcSSc for vWF may identify a group at risk of developing PAH. These patients could potentially be targeted with agents that stabilize the endothelium, e.g. statins.

Neutrophil-derived reactive oxygen species in SSc.

OBJECTIVE: Reactive oxygen species (ROS) are implicated in the pathogenesis of SSc. Neutrophils constitute a major source of ROS during inflammation. Here, we examined endogenous and stimulated ex vivo ROS production of SSc neutrophils compared with control neutrophils with and without prior priming with TNF-α. METHODS: ROS generation was measured using luminol-enhanced chemiluminescence. Neutrophils isolated from SSc patients and healthy controls were unprimed or were primed with TNF-α. ROS production was stimulated in vitro with phorbol 12-myristate 13-acetate (PMA) and formyl-met-leu-phe (fMLP). To examine the effects of serum mediators on ROS generation, control neutrophils were also stimulated with SSc or control serum. RESULTS: Neutrophil stimulation with PMA and fMLP resulted in a greater increase in ROS generation in SSc neutrophils compared with controls. However, unstimulated SSc neutrophils generated lower levels of ROS than controls. SSc neutrophils demonstrated an increased response to fMLP in the absence of in vitro TNF-α priming indicating priming of SSc neutrophils in vivo. SSc serum did not stimulate neutrophil ROS generation in vitro. CONCLUSION: SSc neutrophils are primed for ROS generation. Neutrophils binding to activated endothelium in SSc, may induce local production of ROS, perpetuating endothelial dysfunction and mediating fibrosis.

The many faces of interleukin-6: the role of IL-6 in inflammation, vasculopathy, and fibrosis in systemic sclerosis.

Interleukin-6 is currently attracting significant interest as a potential therapeutic target in systemic sclerosis (SSc). In this paper, the biology of interleukin-6 is reviewed, and the evidence for interleukin-6 dysregulation in SSc is explored. The role of inteleukin-6 classical and trans signalling pathways in SSc relevant phenomena such as chronic inflammation, autoimmunity, endothelial cell dysfunction, and fibrogenesis is discussed. The existing evidence that interventions designed to block interleukin-6 signalling are of therapeutic relevance in SSc is evaluated.

Relative α1-anti-trypsin deficiency in systemic sclerosis.

OBJECTIVE: Neutrophil elastase is secreted by neutrophils during activation and circulates in the plasma where it can play a role in inflammation and fibrosis. This study examines the role of neutrophil elastase in SSc, a systemic CTD that is typified by vascular dysfunction, tissue fibrosis and inflammation. METHODS: Serum neutrophil elastase and α1-anti-trypsin concentrations were assessed in SSc patients and healthy controls by ELISA. Serum neutrophil elastase activity was assessed by the elastase-dependent conversion of methoxy-succinyl-alanyl-alanyl-prolyl-valyl-p-nitroanilide to p-nitroanilide using a colourimetric assay. Elastase concentration and activity were correlated with clinical disease features. RESULTS: Serum neutrophil elastase concentration and activity were equivalent in patients and controls; however, in SSc serum, there was an increase in elastase activity for each unit of elastase concentration (P = 0.03). This was due to a decrease in serum α1-anti-trypsin concentrations (P = 0.04). Serum elastase concentration (P = 0.03) and activity (P = 0.02) were significantly lower in RNP-positive patients and serum elastase concentrations were lower in ANA-positive patients (P = 0.003). CONCLUSIONS: Relative deficiency in serum α1-anti-trypsin concentrations in SSc could have important and pathogenically relevant effects since elastase has pro-inflammatory and pro-fibrotic roles. Elastase inhibitors are available in clinical practice and could represent potential therapeutic options in SSc.

Endothelial activation and apoptosis mediated by neutrophil-dependent interleukin 6 trans-signalling: a novel target for systemic sclerosis?

OBJECTIVES: Systemic sclerosis (SSc) is a connective tissue disease associated with significant morbidity and mortality and generally inadequate treatment. Endothelial cell activation and apoptosis are thought to be pivotal in the pathogenesis of this disease, but the mechanisms that mediate this remain unknown. METHODS: Human dermal microvascular endothelial cells were cultured with healthy control neutrophils in the presence of 25% healthy control or SSc serum for 24 h. Apoptosis was measured by annexin V-FITC binding and endothelial cell activation was measured using an allophycocyanin-conjugated E-selectin antibody. Fluorescence was quantified and localised using confocal microscopy. RESULTS: SSc serum resulted in significantly increased apoptosis (p=0.006) and E-selectin expression (p=0.00004) in endothelial cells compared with control serum, effects that were critically dependent on the presence of neutrophils. Recombinant interleukin 6 (IL-6) reproduced these findings. Immunodepletion of IL-6 and the use of an IL-6 neutralising antibody decreased the effect of SSc serum on E-selectin expression. Soluble gp130, which specifically blocks IL-6 trans-signalling, negated the effect of SSc serum on both E-selectin expression and apoptosis. CONCLUSIONS: SSc serum induces endothelial cell activation and apoptosis in endothelial cell-neutrophil co-cultures, mediated largely by IL-6 and dependent on the presence of neutrophils. Together with other pathologically relevant effects of IL-6, these data justify further exploration of IL-6 as a therapeutic target in SSc.