Mortality and major disease risk among migrants of the 1991–2001 Balkan wars to Sweden: A register-based cohort study

BackgroundIn recent decades, millions of refugees and migrants have fled wars and sought asylum in Europe. The aim of this study was to quantify the risk of mortality and major diseases among migrants during the 1991–2001 Balkan wars to Sweden in comparison to other European migrants to Sweden during the same period.Methods and findingsWe conducted a register-based cohort study of 104,770 migrants to Sweden from the former Yugoslavia during the Balkan wars and 147,430 migrants to Sweden from 24 other European countries during the same period (1991–2001). Inpatient and specialized outpatient diagnoses of cardiovascular disease (CVD), cancer, and psychiatric disorders were obtained from the Swedish National Patient Register and the Swedish Cancer Register, and mortality data from the Swedish Cause of Death Register. Adjusting for individual-level data on sociodemographic characteristics and emigration country smoking prevalence, we used Cox regressions to contrast risks of health outcomes for migrants of the Balkan wars and other European migrants. During an average of 12.26 years of follow-up, being a migrant of the Balkan wars was associated with an elevated risk of being diagnosed with CVD (HR 1.39, 95% CI 1.34–1.43, p < 0.001) and dying from CVD (HR 1.45, 95% CI 1.29–1.62, p < 0.001), as well as being diagnosed with cancer (HR 1.16, 95% CI 1.08–1.24, p < 0.001) and dying from cancer (HR 1.27, 95% CI 1.15–1.41, p < 0.001), compared to other European migrants. Being a migrant of the Balkan wars was also associated with a greater overall risk of being diagnosed with a psychiatric disorder (HR 1.19, 95% CI 1.14–1.23, p < 0.001), particularly post-traumatic stress disorder (HR 9.33, 95% CI 7.96–10.94, p < 0.001), while being associated with a reduced risk of suicide (HR 0.68, 95% CI 0.48–0.96, p = 0.030) and suicide attempt (HR 0.57, 95% CI 0.51–0.65, p < 0.001). Later time period of migration and not having any first-degree relatives in Sweden at the time of immigration were associated with greater increases in risk of CVD and psychiatric disorders. Limitations of the study included lack of individual-level information on health status and behaviors of migrants at the time of immigration.ConclusionsOur findings indicate that migrants of the Balkan wars faced considerably elevated risks of major diseases and mortality in their first decade in Sweden compared to other European migrants. War migrants without family members in Sweden or with more recent immigration may be particularly vulnerable to adverse health outcomes. Results underscore that persons displaced by war are a vulnerable group in need of long-term health surveillance for psychiatric disorders and somatic disease.

Edda Bjork Thordardottir and co-workers study health outcomes among migrants from the former Yugoslavia to Sweden.     

Bone microarchitecture in ankylosing spondylitis and the association with bone mineral density,fractures, and syndesmophytes

Introduction

Osteoporosis of the axial skeleton is a known complication of ankylosing spondylitis (AS), but bone loss affecting the peripheral skeleton is less studied. This study on volumetric bone mineral density (vBMD) and bone microarchitecture in AS was conducted to compare peripheral vBMD in AS patients with that in healthy controls, to study vBMD in axial compared with peripheral bone, and to explore the relation between vertebral fractures, spinal osteoproliferation, and peripheral bone microarchitecture and density.

Methods

High-resolution peripheral quantitative computed tomography (HRpQCT) of ultradistal radius and tibia and QCT and dual-energy x-ray absorptiometry (DXA) of lumbar spine were performed in 69 male AS patients (NY criteria). Spinal radiographs were assessed for vertebral fractures and syndesmophyte formation (mSASSS). The HRpQCT measurements were compared with the measurements of healthy controls.

Results

The AS patients had lower cortical vBMD in radius (P = 0.004) and lower trabecular vBMD in tibia (P = 0.033), than did the controls. Strong correlations were found between trabecular vBMD in lumbar spine, radius (r_S = 0.762; P < 0.001), and tibia (r_S = 0.712; P < 0.001).When compared with age-matched AS controls, patients with vertebral fractures had lower lumbar cortical vBMD (-22%; P = 0.019), lower cortical cross-sectional area in radius (-28.3%; P = 0.001) and tibia (-24.0%; P = 0.013), and thinner cortical bone in radius (-28.3%; P = 0.001) and tibia (-26.9%; P = 0.016).mSASSS correlated negatively with trabecular vBMD in lumbar spine (r_S = -0.620; P < 0.001), radius (r_S = -0.400; p = 0.001) and tibia (r_S = -0.475; p < 0.001) and also with trabecular thickness in radius (r_S = -0.528; P < 0.001) and tibia (r_S = -0.488; P < 0.001).Adjusted for age, syndesmophytes were significantly associated with decreasing trabecular vBMD, but increasing cortical vBMD in lumbar spine, but not with increasing cortical thickness or density in peripheral bone. Estimated lumbar vBMD by DXA correlated with trabecular vBMD measured by QCT (r_S = 0.636; P < 0.001).

Conclusions

Lumbar osteoporosis, syndesmophytes, and vertebral fractures were associated with both lower vBMD and deteriorated microarchitecture in peripheral bone. The results indicate that trabecular bone loss is general, whereas osteoproliferation is local in AS.     

Calprotectin (S100A8/9) as serum biomarker for clinical response in proof-of-concept trials in axial and peripheral spondyloarthritis

Introduction

Biomarkers complementing clinical evaluations may help to reduce the length and size of proof-of-concept (PoC) trials aimed to obtain quick “go/no go” decisions in the clinical development of new treatments. We aimed to identify and validate serum biomarkers with a high sensitivity to change upon effective treatment in spondyloarthritis (SpA) PoC trials.

Methods

The candidate biomarkers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), pentraxin-3 (PTX-3), alpha-2-macroglobulin (alpha-2-MG), matrix metalloproteinase-3 (MMP-3), calprotectin, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA) in healthy controls (n = 20) and SpA patients before and after 2 weeks of infliximab (n = 18) or placebo (n = 19) treatment in cohort 1. Clinical outcome was evaluated at week 12. Results were validated in ankylosing spondylitis (AS) with infliximab (cohort 2, n = 21) and peripheral SpA with etanercept (cohort 3, n = 20).

Results

Serum levels of calprotectin, hs-CRP, PTX-3, VEGF (all P < 0.001) and MMP-3 (P = 0.062), but not IL-6 and alpha-2-MG, were increased in SpA versus healthy controls. Treatment with infliximab, but not placebo, significantly decreased calprotectin (P < 0.001) and hs-CRP (P < 0.001) levels, with a similar trend for MMP-3 (P = 0.063). The standardized response mean (SRM), which reflects the ability to detect changes over time, was high for calprotectin (−1.26), good for hs-CRP (−0.96) and moderate for MMP-3 (−0.52). Calprotectin and hs-CRP, but not MMP-3, were good biomarkers for treatment response in axial and peripheral SpA as evaluated and confirmed in cohort 2 and 3 respectively.

Conclusions

Calprotectin and hs-CRP are good serum biomarkers with high sensitivity to change upon effective treatment at the group level in small-scale, short term PoC trials in SpA.     

Peripheral blood CD4+CD25+CD127low regulatory T cells are significantly increased by tocilizumab treatment in patients with rheumatoid arthritis: increase in regulatory T cells correlates with clinical response

IntroductionTocilizumab (TCZ), an anti-interleukin-6 receptor antibody, is clinically effective against rheumatoid arthritis (RA), and several reports have indicated how TCZ influences a number of mechanisms underlying RA pathogenesis. However, it is still unclear whether TCZ affects inflammatory cells in peripheral blood and whether any such changes are associated with clinical response. We evaluated associations between proportions of subsets of peripheral immune cells and clinical response in patients with RA treated with TCZ.MethodsThirty-nine consecutive patients with RA who started to receive TCZ as their first biologic between March 2010 and April 2012 were enrolled. The proportions of several subsets of peripheral cells with their levels of expression of differentiation markers, activation markers and costimulatory molecules were measured sequentially from baseline to week 52 by flow cytometry analysis.ResultsClinical Disease Activity Index (CDAI) remission was achieved in 53.8% of patients at week 52 of TCZ therapy. The proportions of CD4⁺CD25⁺CD127^low regulatory T cells (T_reg) and HLA-DR⁺ activated T_reg cells significantly increased with TCZ therapy (P < 0.001 and P < 0.001, respectively), whereas proportions of CD3⁺CD4⁺CXCR3⁻CCR6⁺CD161⁺ T helper 17 cells did not change over the 52 weeks. The proportions of CD20⁺CD27⁺ memory B cells, HLA-DR⁺CD14⁺ and CD69⁺CD14⁺ activated monocytes, and CD16⁺CD14⁺ monocytes significantly decreased (P < 0.001, P < 0.001, P < 0.001 and P < 0.001, respectively). Among them, only the change in T_reg cells was inversely correlated with the change in CDAI score (ρ = −0.40, P = 0.011). The most dynamic increase in T_reg cells was observed in the CDAI remission group (P < 0.001).ConclusionThis study demonstrates that TCZ affected proportions of circulating immune cells in patients with RA. The proportion of T_reg cells among CD4⁺ cells correlated well with clinical response.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0526-4) contains supplementary material, which is available to authorized users.     

An important role for A20-binding inhibitor of nuclear factor-kB-1 (ABIN1) in inflammation-mediated endothelial dysfunction: an in vivo study in ABIN1 (D485N) mice

IntroductionThe link between cardiovascular disease (CVD) and patients with chronic inflammation is not clearly understood. We examined a knock-in mouse expressing a poly-ubiquitin-binding-defective mutant of the protein ABIN1 (ABIN1(D485N)), which develops a systemic lupus erythematosus-like autoimmune disease because of the hyperactivation of IκB kinases (IκKs) and mitogen-activated protein kinases (MAPKs). These mice were used to determine the potential role of these signaling pathways in inflammation-mediated CVD development.MethodsLaser Doppler imaging in combination with the iontophoresis of vasoactive chemicals were used to assess endothelium-dependent vasodilatation in vivo in ABIN1 (D485N)) mutant defective (n = 29) and wild-type (WT) control (n = 26) mice. Measurements were made at baseline, and animals were subdivided to receive either chow or a proatherogenic diet for 4 weeks, after which, follow-up assessments were made. Paired and unpaired t tests, and ANOVA with post hoc Bonferroni correction were used for statistical significance at P <0.05.ResultsEndothelium-dependent vasodilatation to acetylcholine was attenuated at 4 weeks in ABIN1(D485N)-chow-fed mice compared with age-matched WT-chow-fed mice (P <0.05). The magnitude of attenuation was similar to that observed in WT-cholesterol-fed animals (versus WT-chow, P <0.01). ABIN1(D485N)-cholesterol-fed mice had the poorest endothelium-dependent responses compared with other groups (P <0.001). ABIN1(D485N)-chow-fed mice had increased plasma interleukin-6 (IL-6) levels (versus WT-chow, P <0.001), and this was further elevated in ABIN1(D485N)-cholesterol-fed mice (versus ABIN1(D485N)-chow; P <0.05). IL-1α was significantly greater in all groups compared with WT-chow (P <0.01). ABIN1(D485N) mice showed significant cardiac hypertrophy (P <0.05).ConclusionsThe ABIN(D485N) mice display endothelial dysfunction and cardiac hypertrophy, which is possibly mediated through IL-6 and, to a lesser degree, IL-1α. These results suggest that the ABIN1-mediated hyperactivation of IKKs and MAPKs might mediate chronic inflammation and CVD development.     

Effectiveness of Integrated HIV Prevention Interventions among Chinese Men Who Have Sex with Men: Evaluation of a 16-City Public Health Program

To examine the impacts of a multi-city HIV prevention public health program (China Global Fund Round 5 Project) on condom use and HIV infection, we analyzed four yearly cross-sectional surveys from 2006 through 2009 among 20,843 men who have sex with men (MSM) in 16 Chinese cities. Self-reported condom use at last sex with a male partner increased from 58% in 2006 to 81% in 2009 (trend test, P<0.001). HIV prevalence increased from 2.3% in 2006 to 5.3% in 2009 (P<0.001). Multivariable logistic regression analysis showed that self-reported receipt of interventions was an independent predictor of increased condom use at last sex with a male partner over time (adjusted odds ratio [aOR], 1.63 in 2006 to 2.33 in 2009; P<0.001), and lower HIV prevalence (aOR, 1.08 in 2006 to 0.45 in 2009; P<0.001). HIV prevalence increased from 2006–2009 for participants with no self-reported receipt of interventions (2.1% in 2006 to 10.3% in 2009) and less so for those with interventions (2.4% to 4.7%). This Chinese public health program had positive impacts on both behaviors and disease rate among MSM population. Escalation of the coverage and intensity of effective interventions is needed for further increasing condom use and for reversing the rising trend of HIV epidemic.     

Carotid artery plaque in women with rheumatoid arthritis and low estimated cardiovascular disease risk: a cross-sectional study

IntroductionWe previously reported that most patients with rheumatoid arthritis (RA) and moderate cardiovascular disease (CVD) risk according to the Systematic COronary Evaluation score (SCORE) experience carotid artery plaque. In this study, we aimed to identify patient characteristics that can potentially predict carotid plaque presence in women with RA and a concurrent low CVD risk according to the SCORE.MethodsA cohort of 144 women with an evaluated low risk of CVD (SCORE value of zero) was assembled amongst 550 consecutive patients with RA that underwent CVD risk factor recording and carotid artery ultrasound. Participants had no established CVD, moderate or severe chronic kidney disease, or diabetes. We assessed carotid plaque(s) presence and its associated patient characteristics.ResultsCarotid artery plaque was present in 35 (24.3%) of women with RA. Age, the number of synthetic disease-modifying agents (DMARDs) and total cholesterol concentrations were independently associated with plaque in multivariable stepwise backward regression analysis (odds ratio (95% confidence interval) = 1.15 (1.07 to 1.24), P <0.0001, 1.51 (1.05 to 2.17), P = 0.03 and 1.66 (1.00 to 2.73) P = 0.04), respectively). The area under the curve (AUC) of the receiver operating curve (ROC) for the association with plaque was 0.807 (P <0.0001), 0.679 (P = 0.001) and 0.599 (P = 0.08) for age, total cholesterol concentrations and number of synthetic DMARDs used, respectively. The optimal cutoff value in predicting plaque presence for age was 49.5 years with a sensitivity and specificity of 74% and 75%, respectively, and for total cholesterol concentration, it was 5.4 mmol/l with a sensitivity and specificity of 63% and 70%, respectively. The plaque prevalence was 37.5% in patients (n = 80; 55.6%) with age >49.5 years or/and total cholesterol concentration of >5.4 mmol/l, respectively, compared to only 7.8% in those (n = 64; 44.4%) with age ≤49.5 years or/and total cholesterol concentration of ≤5.4 mmol/l, respectively.ConclusionsApproximately one-third of women with RA who experience a low SCORE value and are aged >49.5 years or/and have a total cholesterol concentration of >5.4 mmol/l, experience high-risk atherosclerosis, which requires intensive CVD risk management.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0576-7) contains supplementary material, which is available to authorized users.     

The natural organosulfur compound dipropyltetrasulfide prevents HOCl-induced systemic sclerosis in the mouse

Introduction

The aim of this study was to test the naturally occurring organosulfur compound dipropyltetrasulfide (DPTTS), found in plants, which has antibiotic and anticancer properties, as a treatment for HOCl-induced systemic sclerosis in the mouse.

Methods

The prooxidative, antiproliferative, and cytotoxic effects of DPTTS were evaluated ex vivo on fibroblasts from normal and HOCl mice. In vivo, the antifibrotic and immunomodulating properties of DPTTS were evaluated in the skin and lungs of HOCl mice.

Results

H₂O₂ production was higher in fibroblasts derived from HOCl mice than in normal fibroblasts (P < 0.05). DPTTS did not increase H₂O₂ production in normal fibroblasts, but DPTTS dose-dependently increased H₂O₂ production in HOCl fibroblasts (P < 0.001 with 40 μM DPTTS). Because H₂O₂ reached a lethal threshold in cells from HOCl mice, the antiproliferative, cytotoxic, and proapoptotic effects of DPTTS were significantly higher in HOCl fibroblasts than for normal fibroblasts. In vivo, DPTTS decreased dermal thickness (P < 0.001), collagen content in skin (P < 0.01) and lungs (P < 0.05), αSMA (P < 0.01) and pSMAD2/3 (P < 0.01) expression in skin, formation of advanced oxidation protein products and anti-DNA topoisomerase-1 antibodies in serum (P < 0.05) versus untreated HOCl mice. Moreover, in HOCl mice, DPTTS reduced splenic B-cell counts (P < 0.01), the proliferative rates of B-splenocytes stimulated by lipopolysaccharide (P < 0.05), and T-splenocytes stimulated by anti-CD3/CD28 mAb (P < 0.001). Ex vivo, it also reduced the production of IL-4 and IL-13 by activated T cells (P < 0.05 in both cases).

Conclusions

The natural organosulfur compound DPTTS prevents skin and lung fibrosis in the mouse through the selective killing of diseased fibroblasts and its immunomodulating properties. DPTTS may be a potential treatment for systemic sclerosis.     

High atherogenic index of plasma and cardiovascular risk factors among Ghanaian breast cancer patients

Comorbidities impact negatively on breast cancer prognosis, especially in developing countries where cases are usually presented to clinics at advanced stages. This study aimed to determine the atherogenic index of plasma (AIP) and cardiovascular risk factors among Ghanaian women diagnosed with breast cancer. A total of 52 breast cancer patients were age-matched with 52 healthy controls. Sociodemographics of participants were obtained using a well-structured questionnaire. Pathological data of patients were obtained from medical records, and all clinical and anthropometric measurements were done using standard instruments. Lipid profile was determined from serum using enzymatic assays, and cardiovascular risk factors were calculated from estimated lipid parameters. Blood pressure, AIP, total cholesterol (T. chol), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) were significantly elevated (P < 0.05) in the breast cancer patients compared to the controls, but the reverse was observed for high-density lipoprotein cholesterol (HDL-c) (P < 0.01). Obesity (odds ratio [OR] = 2.51, P = 0.015), hypertension (OR = 4.04, P < 0.001), AIP (OR = 10.44, P < 0.001), and dyslipidemia (P < 0.01) were significantly associated with breast cancer. AIP correlated positively with age (r = 0.244, P < 0.05), body mass index (r = 0.225, P < 0.05), blood pressure (P < 0.01), T. chol (r =0.418, P< 0.01), and TG (r = 0.880, P < 0.01), but inversely correlated with HDL-c (r = −0.460, P < 0.01). A greater proportion (88%) of the patients presented with advanced breast cancer. AIP and cardiovascular risk factors were high in the breast cancer patients. Considering that AIP and cardiovascular disease risk factors are of interest in breast cancer patients, further studies are needed to understand the effect of AIP and cardiovascular risk factors on breast cancer outcomes.     

Epitope analysis of anti-myeloperoxidase antibodies in propylthiouracil-induced antineutrophil cytoplasmic antibody-associated vasculitis

Introduction

Increasing evidence has suggested that linear epitopes of antineutrophil cytoplasmic antibody (ANCA) directed to myeloperoxidase (MPO) might provide clues to the pathogenesis of propylthiouracil (PTU)-induced ANCA-associated vasculitis (AAV). This study mapped epitopes of MPO-ANCA in sera from patients with PTU-induced MPO-ANCA (with or without vasculitis) and primary AAV, aiming to analyze certain epitopes associated with the development of PTU-induced AAV.

Methods

Six recombinant linear fragments, covering the whole amino acid sequence of a single chain of MPO, were produced from Escherichia coli. Sera from 17 patients with PTU-induced AAV, 17 patients with PTU-induced MPO-ANCA but without clinical evidence of vasculitis, and 64 patients with primary AAV were collected at presentation. Of the 17 patients with PTU-induced AAV, 12 also had sera at remission. The epitope specificities were detected by enzyme-linked immunosorbent assay by using the recombinant fragments as solid-phase ligands.

Results

Compared with patients with PTU-induced MPO-ANCA but without clinical vasculitis, sera from PTU-induced AAV patients showed significantly higher reactivity against the H1 fragment of MPO (optical density values: 0.17 (0.10 to 0.35) versus 0.10 (0.04 to 0.21), P = 0.038) and could recognize a significantly higher number of fragments (two (none to four) versus one (none to two), P = 0.026). Compared with sera from primary AAV patients, sera from PTU-induced AAV patients had significantly higher reactivity to the P fragment and the H4 fragment (47.1% versus 14.1% P < 0.001; 41.2% versus 14.1%, P = 0.034, respectively), and could recognize a significantly higher number of fragments (two (none to four) versus one (none to two), P = 0.013]. Among the 12 PTU-induced AAV patients with sequential samples, the number of fragments recognized in remission was significantly less than that in initial onset (two (none to four) versus none (none to 0.75), P < 0.001].

Conclusions

Linear epitopes of MPO molecules might be associated closely with PTU-induced AAV. In particular, the P and H4 fragments may be important epitopes in PTU-induced AAV.     

The Association of Platelet Count with Clinicopathological Significance and Prognosis in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

ObjectiveElevated platelet count (PC), a measure of systemic inflammatory response, is inconsistently reported to be associated with poor prognosis in patients with renal cell carcinoma (RCC). We conducted a systematic review and meta-analysis to clarify the significance of PC in RCC prognosis.MethodsPubMed, Embase, and Web of Science databases were searched to identify eligible studies to evaluate the associations of PC with patient survival and clinicopathological features of RCC.ResultsWe analyzed 25 studies including 11,458 patients in the meta-analysis and categorized the included articles into three groups based on RCC stage. An elevated PC level was associated with poor overall survival (OS, hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.87-2.67, P<0.001) and cancer-specific survival (CSS, HR 2.59, 95% CI 1.92-3.48, P<0.001) when all stages were examined together; with poor CSS (HR 5.09, 95% CI 2.41-10.73, P<0.001) and recurrence-free survival (HR 6.68, 95% CI 3.35-13.34, P<0.001) for localized RCC; with poor OS (HR 2.00, 95% CI 1.75-2.28, P<0.001) for metastatic RCC; and with poor OS (HR 2.05, 95% CI 1.04-4.03, P = 0.038), CSS (HR 3.38, 95% CI 1.86-6.15, P<0.001), and PFS (HR 2.97, 95% CI 1.47-6.00, P = 0.002) for clear cell RCC. Furthermore, an elevated PC level was significantly associated with TNM stage (OR 3.11, 95% CI 1.59-6.06, P = 0.001), pathological T stage (OR 3.13, 95% CI 2.60-3.77, P<0.001), lymph node metastasis (OR 4.01, 95% CI 2.99-5.37, P<0.001), distant metastasis (OR 3.85, 95% CI 2.46-6.04, P<0.001), Fuhrman grade (OR 3.70, 95% CI 3.00-4.56, P<0.001), tumor size (OR 4.69, 95% CI 2.78-7.91, P<0.001) and Eastern Cooperative Oncology Group score (OR 5.50, 95% CI 3.26-9.28, P<0.001).ConclusionAn elevated PC level implied poor prognosis in patients with RCC and could serve as a readily available biomarker for managing this disease.     

Obstetrical outcomes and maternal morbidities associated with COVID-19 in pregnant women in France: A national retrospective cohort study

BackgroundTo the best of our knowledge, no study has exhaustively evaluated the association between maternal morbidities and Coronavirus Disease 2019 (COVID-19) during the first wave of the pandemic in pregnant women. We investigated, in natural conceptions and assisted reproductive technique (ART) pregnancies, whether maternal morbidities were more frequent in pregnant women with COVID-19 diagnosis compared to pregnant women without COVID-19 diagnosis during the first wave of the COVID-19 pandemic.Methods and findingsWe conducted a retrospective analysis of prospectively collected data in a national cohort of all hospitalizations for births ≥22 weeks of gestation in France from January to June 2020 using the French national hospitalization database (PMSI). Pregnant women with COVID-19 were identified if they had been recorded in the database using the ICD-10 (International Classification of Disease) code for presence of a hospitalization for COVID-19. A total of 244,645 births were included, of which 874 (0.36%) in the COVID-19 group. Maternal morbidities and adverse obstetrical outcomes among those with or without COVID-19 were analyzed with a multivariable logistic regression model adjusted on patient characteristics. Among pregnant women, older age (31.1 (±5.9) years old versus 30.5 (±5.4) years old, respectively, p < 0.001), obesity (0.7% versus 0.3%, respectively, p < 0.001), multiple pregnancy (0.7% versus 0.4%, respectively, p < 0.001), and history of hypertension (0.9% versus 0.3%, respectively, p < 0.001) were more frequent with COVID-19 diagnosis. Active smoking (0.2% versus 0.4%, respectively, p < 0.001) and primiparity (0.3% versus 0.4%, respectively, p < 0.03) were less frequent with COVID-19 diagnosis. Frequency of ART conception was not different between those with and without COVID-19 diagnosis (p = 0.28).When compared to the non-COVID-19 group, women in the COVID-19 group had a higher frequency of admission to ICU (5.9% versus 0.1%, p < 0.001), mortality (0.2% versus 0.005%, p < 0.001), preeclampsia/eclampsia (4.8% versus 2.2%, p < 0.001), gestational hypertension (2.3% versus 1.3%, p < 0.03), postpartum hemorrhage (10.0% versus 5.7%, p < 0.001), preterm birth at <37 weeks of gestation (16.7% versus 7.1%, p < 0.001), <32 weeks of gestation (2.2% versus 0.8%, p < 0.001), <28 weeks of gestation (2.4% versus 0.8%, p < 0.001), induced preterm birth (5.4% versus 1.4%, p < 0.001), spontaneous preterm birth (11.3% versus 5.7%, p < 0.001), fetal distress (33.0% versus 26.0%, p < 0.001), and cesarean section (33.0% versus 20.2%, p < 0.001). Rates of pregnancy terminations ≥22 weeks of gestation, stillbirths, gestational diabetes, placenta praevia, and placenta abruption were not significantly different between the COVID-19 and non-COVID-19 groups. The number of venous thromboembolic events was too low to perform statistical analysis. A limitation of this study relies in the possibility that asymptomatic infected women were not systematically detected.ConclusionsWe observed an increased frequency of pregnant women with maternal morbidities and diagnosis of COVID-19 compared to pregnant women without COVID-19. It appears essential to be aware of this, notably in populations at known risk of developing a more severe form of infection or obstetrical morbidities and in order for obstetrical units to better inform pregnant women and provide the best care. Although causality cannot be determined from these associations, these results may be in line with recent recommendations in favor of vaccination for pregnant women.

In a national retrospective study, Sylvie Epelboin and colleagues investigate obstetrical outcomes and maternal morbidities among pregnant women with a COVID-19 diagnosis in France.     

Utility of a novel inflammatory marker,GlycA, for assessment of rheumatoid arthritis disease activity and coronary atherosclerosis

IntroductionGlycA is a novel inflammatory biomarker measured using nuclear magnetic resonance (NMR). Its NMR signal primarily represents glycosylated acute phase proteins. GlycA was associated with inflammation and development of cardiovascular disease in initially healthy women. We hypothesized that GlycA is a biomarker of disease activity and is associated with coronary artery atherosclerosis in patients with rheumatoid arthritis (RA).MethodsWe conducted a cross-sectional study of 166 patients with RA and 90 control subjects. GlycA was measured from an NMR signal originating from N-acetylglucosamine residues on circulating glycoproteins. The relationship between GlycA and RA disease activity (Disease Activity Score based on 28 joints (DAS28)) and coronary artery calcium score was determined.ResultsGlycA concentrations were higher in patients with RA (median (interquartile range): 398 μmol/L (348 to 473 μmol/L)) than control subjects (344 μmol/L (314 to 403 μmol/L) (P < 0.001). In RA, GlycA was strongly correlated with DAS28 based on erythrocyte sedimentation rate (DAS28-ESR) and DAS28 based on C-reactive protein (DAS28-CRP) and their components, including tender and swollen joint counts, global health score, ESR and CRP (all P < 0.001). The area under the receiver operating characteristic curve for GlycA’s ability to differentiate between patients with low versus moderate to high disease activity based on DAS28-CRP was 0.75 (95 % confidence interval (CI): 0.68, 0.83). For each quartile increase in GlycA, the odds of having coronary artery calcium increased by 48 % (95 % CI: 4 %, 111 %), independent of age, race and sex (P = 0.03).ConclusionGlycA is a novel inflammatory marker that may be useful for assessment of disease activity and is associated with coronary artery atherosclerosis in patients with RA.     

Racial disparities in total ankle arthroplasty utilization and outcomes

IntroductionThe objective of this study was to examine the racial disparities in total ankle arthroplasty (TAA) utilization and outcomes.MethodsWe used the National Inpatient Sample (NIS) to study the time-trends. Race was categorized as White and Black. Utilization rates were calculated for the U.S. general population per 100,000. Hospital length of stay, discharge disposition and mortality after TAA were assessed. We used the Cochran Armitage trend test to assess time-trends from 1998 to 2011 and chi-square test to compare TAA utilization. We used analysis of variance or chi-squared test to compare the characteristics of Whites and Blacks undergoing TAA and logistic regression to compare mortality, length of stay and discharge to home versus medical facility.ResultsThe mean ages for Whites undergoing TAA were 62 years and for Blacks was 52 years. Significant racial disparities were noted in TAA utilization rates (/100,000) in 1998, 0.14 in Whites vs. 0.07 in Blacks (P < 0.0001; 2-fold) and in 2011, 1.17 in Whites vs. 0.33 in Blacks (P < 0.0001; 4-fold). Racial disparities in TAA utilization increased significantly from 1998 to 2011 (P < 0.0001). There was a trend towards statistical significance for the difference in the length of hospital stay in Blacks vs. Whites (52.9% vs. 44.3% with length of hospital stay higher than the median; P = 0.08). Differences in the proportion discharged to an inpatient medical facility after TAA, 16.6% Blacks vs. 13.4% Whites, were not significant (P = 0.36).ConclusionsThis study demonstrated significant racial disparities with lower TAA utilization and suboptimal outcomes in Blacks compared to Whites. Further studies are needed to understand the mediators of these disparities and to assess whether these mediators can be targeted to reduce racial disparities in TAA.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0589-2) contains supplementary material, which is available to authorized users.     

Clinical Characteristics and Risk Factors of Pyogenic Spondylitis Caused by Gram-Negative Bacteria

BackgroundThere are limited data describing the clinical characteristics of pyogenic spondylitis caused by Gram-negative bacteria (GNB). The aim of this study was to investigate the predisposing factors and clinical characteristics of pyogenic spondylitis caused by GNB compared to Gram-positive cocci (GPC).MethodsWe performed a retrospective review of medical records from patients with culture-confirmed pyogenic spondylitis at four tertiary teaching hospitals over an 8-year period.ResultsA total of 344 patients with culture-confirmed pyogenic spondylitis were evaluated. There were 62 patients (18.0%) with pyogenic spondylitis caused by GNB and the most common organism was Escherichia coli (n = 35, 10.2%), followed by Pseudomonas aeruginosa (n = 10, 2.9%). Pyogenic spondylitis caused by GNB was more frequently associated with the female gender (64.5 vs. 35.5%, P <0.01), preexisting or synchronous genitourinary tract infection (32.3 vs. 2.1%, P< 0.01), and intra-abdominal infection (12.9 vs. 0.4%, P< 0.01) compared to patients with GPC. Although pyogenic spondylitis caused by GNB presented with severe sepsis more frequently (24.2 vs. 11.3%, P = 0.01), the mortality rate (6.0 vs. 5.2%) and the proportion of patients with residual disability (6.0 vs. 9.0%), defined as grade 3 or 4 (P = 0.78) 3 months after completion of treatment, were not significantly different compared to GPC patients.ConclusionGNB should be considered as the etiologic organism when infectious spondylitis develops in a patient with preexisting or synchronous genitourinary tract and intra-abdominal infection. In addition, the mortality rate and clinical outcomes are not significantly different between pyogenic spondylitis caused by GNB and GPC.     

Increased oxidative phosphorylation in lymphocytes does not atone for decreased cell numbers after burn injury

The acute systemic inflammatory response syndrome (SIRS) and multiorgan dysfunction (MOD) that occur in large burn injuries may be attributed, in part, to immunosuppressive responses such as decreased lymphocytes. However, the mitochondrial bioenergetics of lymphocytes after severe burn injury are poorly understood. The purpose of this study was to examine mitochondrial function of lymphocytes following severe burns in a swine model. Anesthetized Yorkshire swine (n = 17) sustained 40% total body surface area full-thickness contact burns. Blood was collected at pre-injury (Baseline; BL) and at 24 and 48 h after injury for complete blood cell analysis, flow cytometry, cytokine analysis, and ficoll separation of intact lymphocytes for high-resolution mitochondrial respirometry analysis. While neutrophil numbers increased, a concomitant decrease was found in lymphocytes (P < 0.001) after burn injury, which was not specific to CD4⁺ or CD8⁺ lymphocytes. No changes in immune cell population were observed from 24 h to 48 h post-injury. IL 12-23 decreased while a transient increase in IL 4 was found from BL to 24h (P < 0.05). CRP progressively increased from BL to 24h (P < 0.05) and 48h (P < 0.001) post-injury. Routine and maximal mitochondrial respiration progressively increased from BL to 24h (P < 0.05) and 48 h post-injury (P < 0.001). No changes were found in leak respiration or residual oxygen consumption. When considering the reduction in lymphocyte number, the total peripheral lymphocyte bioenergetics per volume of blood significantly decreased from BL to 24h and 48h (P < 0.05). For the first time, we were able to measure mitochondrial activity in intact lymphocyte mitochondria through high-resolution respirometry in a severely burned swine model. Our data showed that the non-specific reduction in peripheral T cells after injury was larger than the increased mitochondrial activity in those cells, which may be a compensatory mechanism for the total reduction in lymphocytes. Additional studies in the metabolic activation of T cell subpopulations may provide diagnostic or therapeutic targets after severe burn injury.     

In vivo pre-activation of monocytes in patients with axial spondyloarthritis

IntroductionInnate immune responses, including monocyte functions, seem to play an important role in the pathogenesis of axial spondyloarthritis (axSpA). Therefore, we characterized the phenotype and functional state of monocytes of patients with axSpA.MethodsFifty-seven patients with axSpA, 11 patients with rheumatoid arthritis (RA), and 29 healthy controls were included in the study. We determined the percentage of classic, intermediate, and non-classic monocytes according to CD14 and CD16 expression and the expression of Toll-like receptor (TLR) 1, 2, and 4 in whole blood by flow cytometry. The percentage of monocytes producing interleukin (IL)-1beta, IL-6, tumor necrosis factor alpha (TNFα), IL-12/23p40, and IL-1 receptor antagonist (IL-1ra) was detected by flow cytometry after stimulation of whole blood without and with different TLR and nucleotide-binding oligomerization domain ligands—i.e., lipopolysaccharide (LPS), fibroblast-stimulating lipopeptid-1, PAM₃CSK₄, and muramyl dipeptide (MDP)—for 5 h. IL-10 production was measured after 18 h of stimulation in supernatants by enzyme-linked immunosorbent assay.ResultsIn patients with axSpA but not patients with RA, we found higher frequencies of classic monocytes than in controls (median of 90.4 % versus 80.4 %, P < 0.05), higher frequencies of monocytes spontaneously producing IL-1beta and IL-1ra (P < 0.05), and a higher percentage of monocytes producing IL-1beta after MDP stimulation (P < 0.05). Elevated cytokine production was confined to axSpA patients under conventional therapy (non-steroidal anti-inflammatory drugs) and not found in patients under TNFα inhibitor treatment. The LPS-induced production of IL-6 and IL-10 was lower in axSpA patients compared with controls (P < 0.05). Monocytic TLR expression was unaffected in patients with axSpA.ConclusionEnhanced spontaneous and MDP-induced cytokine secretion by monocytes suggests in vivo pre-activation of monocytes in axSpA patients under conventional therapy which is reverted under TNF inhibitor treatment.