The Long-term Effects of Open and Endovascular Aneurysm Repair on Circulating Interleukin-6

Interleukin-6 (IL-6) is associated with abdominal aortic aneurysm (AAA) development and is an independent risk factor for cardiovascular mortality. We tested the hypothesis that aneurysm repair reduces circulating IL-6 by comparing concentrations in patients with large AAA awaiting repair (n = 50) with patients having undergone open (n = 34) or endovascular (n = 66) repair. Only open repair was associated with a significant reduction in IL-6 (p = 0.025). These results suggest that AAAs remain biologically active following endovascular repair. Aneurysm-derived IL-6 may have serious implications for cardiovascular health, and attention should be directed to modifying cardiovascular risk factors in these patients, even after successful aneurysm repair.     

Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts)

ObjectivesTo assess the impact of single nucleotide polymorphisms (SNPs) in IL-2RA (rs2104286) and IL-2RB (rs743777 and rs3218253) genes on the risk of erosions in rheumatoid arthritis (RA) patients.MethodsThis work is derived from 2 prospective cohorts of early RA: ESPOIR (n = 439) and RMP (n = 180). The proportions of patients with erosions at baseline and 1 year according to the genotypes of IL2RA (rs2104286) or the haplotypes constructed with the 2 SNPs of IL2RB were compared in the whole population and in ACPA positive patients. A meta-analysis assessing the risk of erosion depending on the haplotypes of the 2 SNPs of IL-2RB was performed using the Mantel-Haenszel method. A multivariate model was used to assess the independent effect of the haplotypes of IL-2RB on the risk of erosions.ResultsThe AC haplotype of IL-2RB carriage was significantly associated with the rate of erosions in ACPA positive patients in ESPOIR cohort (rate of erosions: AC/AC: 78% versus GC or GT/GC or GT: 44%, p = 0.001). A meta-analysis of ESPOIR and RMP cohorts confirmed that the carriage of AC haplotype was significantly associated with the rate of erosions at 1 year in the whole sample (OR[95%CI] = 1.92[1.14–3.22], p = 0.01) and in ACPA positive patients (OR[95%CI] = 3.34[1.68–6.67], p = 0.0006). A multivariate model in ESPOIR cohort demonstrated the independent effect of the carriage of the AC haplotype (6.03[1.94–18.69], p = 0.002) on the risk of erosions in ACPA+ patients.ConclusionA haplotype constructed with 2 SNPs located on IL-2RB gene was associated with erosive status in early RA.     

Splanchnic Microcirculation Protection by Hydroxyethyl Starches During Abdominal Aortic Aneurysm Surgery

ObjectiveTo specifically compare the effect of two hydroxyethyl starches (HES) on the splanchnic microcirculation and systemic inflammation during abdominal aortic aneurysm (AAA) surgery.Materials and methodsA prospective randomised study was carried out on 62 patients who received HES of molecular-weight 200 kDa (HES200/0.62), 130 kDa (HES130/0.4) or gelatine for 24 h peri-operatively. Gastric-mucosal pHi (GpHi) and anti-endotoxin antibody were used as markers of splanchnic perfusion and endotoxaemia respectively. C-reactive protein (CRP) and lung-injury score (LIS) were used as markers of systemic inflammation and end-organ dysfunction respectively. Data was collected prospectively.ResultsThe drop in GpHi was least with HES200/0.62 compared to HES130/0.4 and gelatine at reperfusion (7.32 vs 7.28 and 7.28, p = 0.017 and 0.009 respectively) and compared to gelatine at 2 h as well (7.43 vs 7.28, p = 0.001). GpHi dropped less with HES130/0.4 compared to gelatine at 2 h (7.39 vs 7.28, p = 0.002). Endotoxaemia increased only with gelatine. CRP was lower with HES200/0.62 (178 mg/mL) than gelatine (221 mg/mL) and HES130/0.4 (223 mg/mL) at 48 h (p = 0.049 and p = 0.009 respectively). There was no difference in LIS but ventilation duration was less with HES200/0.62 compared with gelatine (4 vs 11 h, p = 0.012).ConclusionDuring AAA surgery, HES200/0.62 provides the best splanchnic microcirculation protection, also reducing inflammation and duration of ventilation (Trial ISRCTN70166506).     

Biomechanical Rupture Risk Assessment of Abdominal Aortic Aneurysms: Model Complexity versus Predictability of Finite Element Simulations

ObjectiveInvestigation of the predictability of finite element (FE) models regarding rupture risk assessment of abdominal aortic aneurysms (AAAs).Materials and materialsPeak wall stress (PWS) and peak wall rupture risk (PWRR) of ruptured (n = 20) and non-ruptured (n = 30) AAAs were predicted by four FE models of different complexities derived from computed tomography (CT) data. Two matching sub-groups of ruptured and non-ruptured aneurysms were used to investigate the usability of different FE models to discriminate amongst them.ResultsAll FE models exhibited a strong positive correlation between PWS and PWRR with the maximum diameter. FE models, which excluded the intra-luminal thrombus (ILT) failed to discriminate between ruptured and non-ruptured aneurysms. The predictability of all applied FE models was strengthened by including wall strength data, that is, computing the PWRR. The most sophisticated FE model applied in this study predicted PWS and PWRR 1.17 (p = 0.021) and 1.43 (p = 0.016) times higher in ruptured than diameter-matched non-ruptured aneurysms, respectively.ConclusionsPWRR reinforces PWS as a biomechanical rupture risk index. The ILT has a major impact on AAA biomechanics and rupture risk, and hence, needs to be considered in meaningful FE simulations. The applied FE models, however, could not explain rupture in all analysed aneurysms.     

Search for Serum Biomarkers Associated with Abdominal Aortic Aneurysm Growth – A Pilot Study

IntroductionSerological biomarkers could reflect asymptomatic infrarenal aortic aneurysm (AAA) activity and guide patient management.ReportSerum concentrations of C-reactive protein (CRP), alpha 1-antitrypsin and lipoprotein(a) were measured in blood samples from 35 AAA patients and 35 controls and correlated with the aortic diameter and AAA growth in the previous 12 months.We found a positive correlation between CRP and AAA diameter (r = 0.46; p = 0.007) and alpha 1-antitrypsin and AAA growth (r = 0.55; p = 0.004).ConclusionsAlpha 1-antitrypsin may be a promising biomarker of AAA growth.     

Prevalence and risk factors for recovery of filamentous fungi in individuals with cystic fibrosis

BackgroundFilamentous fungi are frequently recovered from respiratory cultures of individuals with CF.MethodsA CF cohort database was utilized to determine filamentous fungal prevalence and risk factors.ResultsThe prevalence of filamentous fungal isolation increased from 2.0% in 1997 to 28.7% in 2007. The odds of isolating filamentous fungi during a quarter was greater in CF adults [p < 0.001], during chronic oral antibiotic use [p = 0.002] and increased with each 10% drop in FEV₁ percent predicted [p = 0.005], while inhaled corticosteroids surprisingly decreased the likelihood [p = 0.012]. The direction of these effects persisted after excluding individuals with ABPA. A sub-analysis determined older age [p = 0.019] and use of inhaled antibiotics [p = 0.011] were independent risk factors for onset of fungal colonization.ConclusionsThis study suggests that isolation of filamentous fungi in CF at JHH has increased and risk factors include older age, decreased lung function, and chronic oral antibiotics.     

Characterisation of Interleukin-8 and Monocyte Chemoattractant Protein-1 Expression within the Abdominal Aortic Aneurysm and their Association with Mural Inflammation

ObjectivesAbdominal aortic aneurysms (AAAs) are characterised by chronic transmural inflammation. This study investigated the expression of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) within the AAA, and their relationship with mural inflammation.MethodsBiopsies were obtained from 25 AAAs, 15 abdominal aortas, and 10 atherosclerotic thoracic aortas. IL-8 and MCP-1 expression was measured in homogenised specimens by ELISA. Infiltrate composition and localised expression of IL-8 and MCP-1 were determined through immunohistochemistry.ResultsELISA analysis demonstrated that IL-8 and MCP-1 were raised in the AAA compared to the controls [(IL-8, AAA vs. abdominal aorta: >28-fold, P < .001; AAA vs. thoracic aorta: >28-fold, P < .001) (MCP-1, AAA vs. abdominal aorta: 9-fold, P < .001; AAA vs. thoracic aorta: 19-fold, P < .001)]. Immunohistochemistry revealed that IL-8 was localised to the inflammatory infiltrate, which consisted predominantly of CD3⁺ T- and CD20⁺ B-lymphocytes. MCP-1 was predominantly expressed by CD68⁺ macrophages. Increasing IL-8 expression was associated with an increase in mural inflammation, and an increase in CD3⁺ T-lymphocytes of CD4⁺ phenotype within the infiltrate population.ConclusionPathways involving IL-8 and MCP-1 may be involved in AAA pathogenesis. IL-8 may be directly involved in the chemotaxis of T_H-lymphocytes into the AAA wall.     

The physiological range of the Böhler’s angle in the adult Croatian population

BackgroundTo examine the relationship of the Böhler’s angle with age, sex, and laterality, and to analyze the interrater agreement.MethodsAfter 248 digital lateral radiographs of the foot were submitted to exclusion criteria, three raters independently measured the Böhler’s angle on the remaining 130 X-rays in PACS. The variables were analyzed with correlation coefficients, and one-way ANOVA. The repeated measures of ANOVA were computed across age groups (30–39, 40–49, 50–59, and 60–69 years). The interrater agreement was calculated using intraclass correlation coefficient (ICC).ResultsThe mean value of the Böhler’s angle was 34 ± 5° (21–46°). It was not related to age (in general [p = 0.057], and across groups [p from 0.107 to 0.122]), sex (p = 0.344; p = 0.342), and laterality (p = 0.618; p = 0.617). The interrater reliability was almost perfect (ICC = 0.94).ConclusionsThe Böhler’s angle was not related to age, sex, and laterality, whereas the interrater agreement was almost perfect.     

Is There a Benefit of Frequent CT Follow-up After EVAR?

ObjectiveImaging follow-up (FU) after endovascular aneurysm repair (EVAR) is usually performed by periodic contrast-enhanced computed tomography (CT) scans. This study aims to evaluate the effectiveness of CT-FU after EVAR.MethodsIn this study, 279 of 304 consecutive patients (261 male, aged 74 years (interquartile range (IQR): 70–79 years) with a median abdominal aortic aneurysm (AAA) diameter of 58 mm (IQR: 53–67 mm)) underwent at least one of the yearly CT scans and plain abdominal films after EVAR. All patients received Zenith stent-grafts for non-ruptured AAAs at a single institution. Patients were considered asymptomatic when a re-intervention was done solely due to an imaging FU finding. The data were prospectively entered in a computer database and retrospectively analysed.ResultsAs a follow-up, 1167 CT scans were performed at a median of 54 months (IQR: 34–74 months) after EVAR. Twenty-seven patients exhibited postoperative AAA expansion (a 5-year expansion-free rate of 88 ± 2%), and 57 patients underwent 78 postoperative re-interventions with a 5-year secondary success rate of 91 ± 2%. Of the 279 patients, 26 (9.3%) undergoing imaging FU benefitted from the yearly CT scans, since they had re-interventions based on asymptomatic imaging findings: AAA diameter expansion with or without endoleaks (n = 18), kink in the stent-graft limbs (n = 4), endoleak type III due to stent-graft limb separation without simultaneous AAA expansion (n = 2), isolated common iliac artery expansion (n = 1) and superior mesenteric artery malperfusion due to partial coverage by the stent-graft fabric (n = 1).ConclusionsLess than 10% of the patients benefit from the yearly CT-FU after EVAR. Only one re-intervention due to partial coverage of a branch by the stent-graft would have been delayed if routine FU had been based on simple diameter measurements and plain abdominal radiograph. This suggests that less-frequent CT is sufficient in the majority of patients, which may simplify the FU protocol, reduce radiation exposure and the total costs of EVAR. Contrast-enhanced CT scans continue, nevertheless, to be critical when re-interventions are planned.     

Collagen gene polymorphisms influence fracture risk and bone mass acquisition during childhood and adolescent growth

Fractures are common in childhood with incidence maximal during puberty, around the time of peak height velocity. The relationships between single nucleotide polymorphisms (SNPs) in COL1A1 and COL1A2, bone mass acquisition, and childhood fractures are unclear.We recruited 394 children and adolescents aged 4 to 16 years into a noninterventional case control study. All had suffered an episode of trauma leading to hospital presentation; 205 had sustained a fracture. We determined the frequency of COL1A1 Sp1 and COL1A2 PvuII SNPs. Lumbar spine dual-energy X-ray absorptiometry (DXA) measurements were compared between fracture and control groups according to genotype. Subgroup analyses were performed according to sex, pubertal status, and site of injury.We found that the COL1A2 ‘PP’ genotype approximately halved the odds of fracture in the study group as a whole (OR = 0.45 [95% CI = 0.24–0.82], p = 0.01). In particular, possession of the same genotype by subjects who had not yet progressed beyond midpuberty was associated with reduced odds of fracture (OR = 0.38 [95% CI = 0.19–0.79], p = 0.01) and significantly increased lumbar spine bone mineral content (p = 0.03) and areal bone mineral density (p = 0.007). The COL1A1 Sp1 binding site ‘s’ allele was associated with a trebling of the odds of fracture in prepubertal children (OR = 3.1 [95% CI = 1.43–6.61], p = 0.004), but there was no association with any DXA measures.This is the first paediatric study to our knowledge that shows an association of the COL1A2 PvuII restriction site ‘PP’ genotype with a reduced risk of fracture and of the COL1A1 Sp1 binding site ‘s’ allele with an increased risk. The association of these variants with fracture risk is greatest during periods of predominantly appendicular bone growth.     

Aortic Length Changes During Abdominal Aortic Aneurysm Formation,Expansion and Stabilisation in a Rat Model

BackgroundDeterminants of extracellular matrix (ECM) destruction/reconstruction balance influencing abdominal aortic aneurysm (AAA) diameter may impact length.ObjectiveDocument aortic lengthening, its correlation to diameter, and determine how treatments that impact diameter also affect length.MethodsThree hundred and fifty-five diameter and length measurements were performed in 308 rats during AAA formation, expansion and stabilisation in guinea pig aortas xenografted in rats. Impact of modulation of ECM destructive/reconstructive balance by endovascular Vascular Smooth Muscle Cell (VSMCs) seeding, TIMP-1, PAI-1 and TGF-beta1 overexpression on length has been assessed.ResultsLength increased in correlation with diameter during formation (correlation coefficient (cc): 0.584, P < 0.0001) and expansion (cc: 0.352, P = 0.0055) of AAAs. Overexpression of TIMP-1 and PAI-1 decreased lengthening (P = 0.02 and 0.014, respectively) demonstrating that elongation is driven by matrix metalloproteinases and their activation by the plasmin pathway. Overexpression of TGF-beta1 controlled length in formed AAAs (17.3 ± 9.6 vs. 5.9 ± 7.4 mm, P = 0.022), but not VSMC seeding, although both therapies efficiently prevented further diameter increase. Length and diameter correlation was lost after biotherapies.ConclusionLength increases in correlation with diameter during AAA formation and expansion, as a consequence of ECM injury driven by MMPs activated by the plasmin pathway. Correlation between length and diameter increases is not universally preserved.     

Mycobacterium avium and Mycobacterium abscessus complex target distinct cystic fibrosis patient subpopulations

BackgroundClinical observations suggest that Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC) may affect cystic fibrosis (CF) patients with different characteristics and risk factors, but this has never been demonstrated within a single prospective cohort.MethodsWe studied 50 MABSC-positive and 23 MAC-positive patients from a French prevalence study of non‐tuberculous mycobacteria (NTM) in CF. Risk factors specifically associated with MABSC and MAC were analyzed by nested case–control studies, with two NTM-negative controls matched by age, sex and center for each case.ResultsMAC-positive patients were significantly older than MABSC-positive patients (mean [SD] age, 23.1 [10.2] vs 17.4 [8.3] years, p = 0.013), and were also older at CF diagnosis (mean [SD] age, 12.9 [16.1] vs 3.1 [7.7] years, p = 0.015); they tended to be less frequent of the ΔF508/ΔF508 genotype (33.3 vs 61.1%, p = 0.17) and to use pancreatic extracts less frequently (82.4 vs 97.6%, p = 0.07). Risk factors identified by multivariate analysis were: i) in the MAC case–control study, an older age at CF diagnosis (p = 0.004); ii) in the MABSC case–control study, at least one course of intravenous antibiotics (p = 0.01) and more frequent isolation of Aspergillus (p = 0.03).ConclusionsMAC affects adult patients with a mild form of CF, whereas MABSC affects younger patients with more severe CF and more frequent intravenous antimicrobial treatment.     

Oncological outcomes of laparoscopic nephroureterectomy with pluck method for distal ureter resection

ObjectiveTo report the oncologic outcomes of upper tract urothelial carcinoma treated with laparoscopic nephroureterectomy and pluck method for distal ureter resection.Materials and methodsBetween May 2004 and November 2015, 118 patients with upper urinary tract urothelial carcinoma received laparoscopic radical nephroureterectomy with endoscopic bladder cuff excision at our institution. The medical records were reviewed retrospectively for clinical and pathological results. Cox regression analyses were performed on factors related to oncological outcomes.ResultsThe median follow-up was 26 months. Bladder recurrence was found in 27 patients (22.9%), extravesical retroperitoneal recurrence in four patients (3.4%), and metastases in 17 patients (14.4%). Multivariate analyses showed that male sex was associated with higher bladder recurrence [odds ratio (OR) = 2.2; 95% confidence interval (CI), 1.02–4.78; p = 0.045)], tumor size had significant correlation with locoregional recurrence (OR = 1.29; 95% CI, 1.07–3.43; p = 0.029), tumor stage was significantly correlated with subsequent metastasis (OR = 2.08; 95% CI, 1.21–3.56; p = 0.008) and overall survival (OR = 1.84; 95% CI, 1.06–3.22 ; p = 0.031), and tumor size correlated significantly with cancer-specific survival (OR = 2.57; 95% CI, 1.16–5.72; p = 0.021).ConclusionsTumor size and tumor stage were significantly associated with survival (cancer-specific and overall survival) in patients receiving nephroureterectomy with pluck method.     

Thoracic paravertebral block versus pectoral nerve block for analgesia after breast surgery

BackgroundPectoral nerve block (Pecs) is a novel interfascial plane block which can provide analgesia after breast surgery while paravertebral block (PVB) is widely used for this purpose. We evaluated the difference between the two techniques in regard to morphine consumption and analgesic efficacy after modified radical mastectomy (MRM).MethodsSixty patients undergoing elective MRM were randomly allocated into either PVB with 15–20 ml of levobupivacaine 0.25% at the level of fourth thoracic vertebra or Pecs block with 10 ml of levobupivacaine 0.25% injected inbetween pectoralis major and pectoralis minor muscle and another 20 ml levobubivacaine 0.25% inbetween pectorlis minor and serratus anterior muscle. Primary outcome measure was morphine consumption in the first 24 h while secondary outcome measures included pain scores, intraoperative fentanyl consumption as well as postoperative nausea and vomiting (PONV).ResultsPostoperative morphine consumed at 24 h was significantly lower in Pecs group [21 (20–25) mg] than in PVB group [28 (22–31) mg], (p = 0.002). Time for first request of morphine was longer in Pecs group [175 (155–220) min] than in PVB group [137.5 (115–165) min], (p < 0.001). Numerical rating score (NRS) at rest was lower in Pecs group compared with PVB group at 1 h, 6 h and 12 h (p < 0.001) but at 18 h and 24 h it was lower in PVB group compared with Pecs group (p = 0.008 and <0.001 respectively). During movement, NRS was significantly lower at 1st hour in Pecs group (p < 0.001) while at 18 h and 24 h it was significantly lower in PVB group (p < 0.001). PONV was comparable between both groups.ConclusionPecs block reduced postoperative morphine consumption in the first 24 and pain scores in the first 12 h in comparison with PVB after mastectomy.     

Simultaneous Aortic and Coronary Assessment in Abdominal Aortic Aneurysm Patients by Thoraco-abdominal 64-Detector-row CT Angiography: Estimate of the Impact on Preoperative Management: A Pilot Study

ObjectivesTo estimate the influence of information on the coronary arteries obtained from routine thoraco-abdominal CT angiography (CTA) on pre-operative clinical management in abdominal aortic aneurysm (AAA) patients.MethodsTwenty-eight AAA patients underwent pre-operative thoraco-abdominal electrocardiography (ECG)-gated 64-detector-row CTA to evaluate aortic pulsatility for prosthesis size matching. Retrospectively, the coronaries were reconstructed from the same data set and scored on a per segment basis for stenosis (0%, ≤50% or >50%) and grading confidence (poor, adequate or high). An experienced cardiologist was presented information on patient characteristics obtained from patient records and CTA findings. Suggested changes in European Society of Cardiology guidelines based patient management based on CTA information were scored.ResultsOn CTA, 17 patients (61%) had significant coronary disease (>50% stenosis) including left main (n = 4), single (n = 7) and multiple (n = 6) vessel disease. Grading confidence was adequate or high in 86% of proximal and middle segments. Based on CTA findings, patient management would have been changed in 4 out of the 28 patients (14%; 95% CI 1–27%) by adding coronary angiography (n = 4). In five patients who underwent coronary artery bypass grafting previously, CT did not change management but confirmed graft patency.ConclusionsInformation on coronary pathology and coronary bypass graft patency can be readily obtained from thoraco-abdominal CTA and may alter pre-operative patient management, as shown in 14% of AAA patients in our study.     

Risk factors for achilles tendon rupture: A matched case control study

PurposeThe purpose of this study was to elucidate whether body mass index (BMI), activity level, and other risk factors predispose patients to Achilles tendon ruptures.Materials and methodsA retrospective review of 279 subjects was performed (93 with Achilles tendon rupture, matched 1:2 with 186 age/sex matched controls with ankle sprains). Demographic variables and risk factors for rupture were tabulated and compared.ResultsThe rupture group mean BMI was 27.77 (95% CI, 26.94–28.49), and the control group mean BMI was 26.66 (95% CI, 26.06–27.27). These populations were found to be statistically equivalent (p = 0.047 and p < 0.001 by two one-sided t-test). A significantly higher proportion of those suffering ruptures reported regular athletic activity at baseline (74%) versus controls (59%, p = 0.013).ConclusionThere was no clinically significant difference found in BMI between patients with ruptures and controls. Furthermore, it was found that patients who sustained ruptures were also more likely to be active at baseline than their ankle sprain counterparts.     

Inter–rater reliability of the simplified Modified Rankin Scale as an outcome measure for treated cerebral aneurysm patients

BackgroundThe modified Rankin scale (mRS) is commonly used as a clinical outcome measure in aneurysm trials, but inter–observer reliability in treated patients has not been tested.MethodsWe reviewed the literature on inter–observer reliability studies of the mRS. Sixty patients with ruptured (n = 47) or unruptured (n = 13) aneurysms treated with endovascular methods (n = 34) or surgical clipping (n = 26) were independently evaluated by a neurosurgeon, a stroke neurologist, and a novice research assistant, and a simplified mRS score assigned. Results were analyzed using Gwet's AC_1/2 reliability coefficients (K_G).ResultsNo previous reports validating the reliability of the mRS in treated aneurysm patients were identified. Using the mRS 0–5, inter–rater agreement was almost perfect (K_G = 0.89 [0.86–0.93]). Agreement between raters remained almost perfect regardless of the rater's expertise. Agreement was almost perfect (K_G = 0.87 [0.77–0.96] when the mRS was dichotomized 0–2 vs 3–5, but fell to moderate when dichotomized 0–1 vs 2–5 (K_G = 0.59 (0.42–0.75). Agreement using the 0–2 vs 3–5 dichotomized mRS remained almost perfect for coiled (K_G = 0.90), clipped (K_G = 0.82), ruptured (K_G = 0.84), and unruptured (K_G = 0.95) aneurysms. Dichotomization of results at 0–1 vs 2–5 would have resulted in an (undesirable) significant difference in good outcomes between raters (P = .003), but not at 0–2 vs 3–5 (P = .52).ConclusionThe simplified mRS appears to be a reliable clinical outcome measure for treated cerebral aneurysm patients. When needed, dichotomization is more reliable at mRS 0–2 vs 3–5 than at 0–1 vs 2–5. The simplified mRS is a promising tool in the functional assessment of aneurysm patients recruited in pragmatic care trials.     

High anti-CCP antibody titres predict good response to rituximab in patients with active rheumatoid arthritis

ObjectivePrevious studies reported that anti-CCP antibody positivity predicts good response to rituximab (RTX) in rheumatoid arthritis (RA). A quantitative approach to such possibility could be a good way to detect the subset of patients most likely to respond. We investigated whether serum anti-CCP antibody titres could predict response to RTX in RA patients.MethodsWe retrospectively investigated RA patients who received RTX. The primary criterion was decrease in DAS28 > 1.2 at 6 months (M6). Secondary efficacy criteria included a good response and remission according to EULAR. Predictors of response were investigated by multivariate logistic regression analysis.ResultsWe included 114 RA patients (81.6% female, median age 53.5 [IQR 45.7–61.2] years, median disease duration 8.5 [4.0–16.0] years). Anti-CCP antibodies were present in 93 patients (81.6%), with median anti-CCP antibody titres 583 [195–1509] U/mL. In all, 44 patients (38.6%) showed decreased DAS28 > 1.2 at M6. On univariate analysis, high anti-CCP titres were associated with response rather than non-response to RTX (median 1122 [355–1755] vs. 386 [149–800] U/mL, P = 0.0191) at M6. On multivariate regression analysis, with a cut-off of 1000 U/mL, anti-CCP antibody titres ≥ 1000 was associated with a decrease in DAS28 > 1.2 (OR 5.10 [1.97–13.2], P = 0.0002); a EULAR good response (4.26 [1.52–11.95], P = 0.0059); and a trend for EULAR remission (2.52 [0.78–8.12], P = 0.1207).ConclusionHigh anti-CCP antibody titres predict response to RTX in RA. This factor, easily assessed in clinical practice, can help with personalized medicine and selecting the best candidates for RTX treatment.     

Elevated serum creatine phosphokinase is associated with mortality and inotropic requirement in critically injured adults

BackgroundHemeproteins such as free myoglobin can undergo autoxidation and catalyse lipid peroxidation, increasing oxidative stress. Creatine phosphokinase (CPK) elevation is a marker for free myoglobin after myocyte damage. Since oxidative injury is a key mechanism of injury-related organ dysfunction, we hypothesised that serum CPK levels correlate with mortality and need for inotropic medication and duration of inotropic support, i.e. shock, among critically injured patients.MethodsWe conducted a retrospective review of 17,847 patients admitted to a single Trauma Intensive Care Unit over 9 years. 2583 patients with serum CPK levels were included in the analysis. Patient data were collected continuously into an electronic ICU repository. Univariate analysis was accomplished using Spearman correlation and the Mann–Whitney U test. Propensity score adjustment models accounting for potential confounders were used to assess the independent effect of CPK level on mortality, need for inotropic support, and duration of inotropic support.ResultsMedian CPK was significantly higher in patients who died (916 [IQR 332, 2472] vs. 711 [253, 1971], p = 0.004) and in those who required inotropic medications (950 [353, 2525] vs. 469 [188, 1220], p < 0.001). After adjusting for propensity score and potential confounders the odds of mortality increased by 1.10 (95% CI 1.02–1.19, p = 0.020) and the odds of inotropic medication use increased by 1.30 (95% CI 1.22–1.38, p < 0.001) per natural log unit increase in CPK. There was a significant association between CPK level and duration of inotropic support (Spearman's rho .237, p < 0.001) that remained significant in a propensity score-adjusted model.ConclusionIn critically injured patients, elevated serum CPK level is independently associated with mortality, need for inotropic medication, and duration of inotropic support. This study is the first to evaluate the relationship of CPK level and mortality in addition to surrogate measures of shock in a population of critically injured patients. If these associations are verified prospectively, there may be a role for treatment with hemeprotein reductants, such as paracetamol, to mitigate the effects of shock and end-organ dysfunction.