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.     

Performance of the American College of Rheumatology/European League Against Rheumatism 2010 criteria for the diagnosis of rheumatoid arthritis in Chinese patients

ObjectivesTo evaluate the ability of American College of Rheumatology (ACR) 2010 classification criteria to diagnose rheumatoid arthritis (RA) compared to the widely used ACR 1987 criteria in Chinese patients.MethodsFour hundred and four patients suffering from arthritis were included in the study. Two hundred and twenty-one of them were classified as RA patients and 183 had alternative diagnoses. The patients were further subdivided into three groups according to their disease duration of within one year, one to two years or more than two years. The diagnostic value of ACR/EULAR 2010 criteria for RA was evaluated by comparing the sensitivity and specificity with those of ACR 1987 criteria in these patients.ResultsThe sensitivity and specificity of ACR/EULAR 2010 criteria for diagnosing RA were 95% and 92.9%, respectively. In contrast, the sensitivity and specificity of ACR 1987 criteria were 81.4% and 92.9%, respectively. The efficacy of ACR/EULAR 2010 criteria was superior to the ACR 1987 criteria by comparing their area under the curves (AUC) (0.940, 95% CI [0.912, 0.967] vs. 0.872, 95% CI [0.835, 0.909]). The recognition accuracy of ACR/EULAR 2010 criteria was higher than that of ACR 1987 criteria (94.5% vs. 86.6%, P < 0.05). Inter-rater analysis showed that agreement of the two criteria was substantial (Kappa = 0.744, P < 0.001). For patients with disease duration within one year, one to two years and over two years, the sensitivities of ACR 1987 criteria were 69.2%, 81.3% and 89.9%, while the specificities were 94.4%, 90.6% and 92%, respectively. The corresponding sensitivities of ACR/EULAR 2010 criteria in these patients were 91%, 93.8% and 98.2%, while the corresponding specificities were 94.4%, 96.6% and 89.3%, respectively. The advantage of ACR/EULAR 2010 criteria over 1987 criteria in higher sensitivity was remarkable particularly in patients with disease duration within one year (P < 0.001).ConclusionsThe ACR/EULAR 2010 criteria is more accurate in RA diagnosis compared to the ACR 1987 criteria by elevating the sensitivity while preserving the specificity, especially in patients with disease duration within one year. The ACR/EULAR 2010 criteria may serve as new diagnostic tools in daily clinical practice.     

There is still a care gap in osteoporosis management for patients with rheumatoid arthritis

ObjectivesTo assess compliance rates with the current Canadian osteoporosis guidelines and whether the Fracture Risk Assessment Tool score in patients with rheumatoid arthritis correlated with the likelihood of receiving osteoporosis treatment and having a bone mineral density test.MethodsCharts of serial outpatients with rheumatoid arthritis were reviewed to collect bone mineral density test data and patients’ use of calcium, vitamin D, and osteoporosis treatment. Odds ratios (OR) were calculated to determine if a higher Fracture Risk Assessment Tool score increased the likelihood of osteoporosis treatment or having a bone mineral density test.ResultsUsing the Fracture Risk Assessment Tool, the 10-year risk of major osteoporotic fracture was high in 92 (12.5%), moderate in 216 (29.3%), and low in 429 (58.2%) patients. Compared to those at low risk, patients identified as high risk were more likely to receive osteoporosis treatment (OR 16.31, 95% CI 9.45–28.13, P < 0.001); calcium (OR 3.89, 95% CI 2.43–6.25, P < 0.001); vitamin D (OR 3.46, 95% CI 2.12–5.64, P < 0.001); and to have had a bone mineral density test (OR 10.22, 95% CI 5.50–18.96, P < 0.001). Among 124 patients currently taking prednisone, half (46.8%) were prescribed a bisphosphonate.ConclusionsAlthough compliance with current osteoporosis guidelines remains low among all patients with rheumatoid arthritis, higher risk patients were more likely to have a bone mineral density test and receive treatment for osteoporosis, as indicated by the clear dose response seen along the 10-year fracture risk from low to high-risk groups.     

HLA association with the susceptibility to anti-synthetase syndrome

ObjectiveTo investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD).MethodsWe conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing.ResultsA statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P = 1.56E–09, odds ratio–OR [95% confidence interval–CI] = 2.54 [1.84–3.50] and 21.4% versus 5.5%, P = 18.95E–18, OR [95% CI] = 4.73 [3.18–7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P = 0.0003, OR [95% CI] = 0.48 [0.31–0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P = 0.001, OR [95% CI] = 2.54 [1.39–4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed.ConclusionsOur results support the association of the HLA complex with the susceptibility to ASSD.     

Efficacy and safety of sugammadex compared to neostigmine for reversal of neuromuscular blockade: a meta-analysis of randomized controlled trials

Background and objectiveSugammadex has been introduced for reversal of rocuronium (or vecuronium)–induced neuromuscular blockade (NMB). Although its efficacy has been established, data are conflicting whether it is safer than neostigmine traditionally used for reversing NMB.DesignMeta-analysis of data about effectiveness and safety of sugammadex compared to neostigmine for reversing NMB in adults was performed using the PRISMA methodology.SettingUniversity medical hospital.MethodsA comprehensive search was conducted using PubMed, Web of Science, and Cochrane Library electronic databases to identify English-language randomized controlled trials. Two reviewers independently selected the trials; extracted data on reversal times, incomplete reversals of NMB, and adverse events (AEs); and assessed the trials' methodological quality and evidence level. Only AEs that were related to study drug by a blinded safety assessor were considered for meta-analysis.PatientsA total of 1384 patients from 13 articles were included in this meta-analysis.Main resultsCompared to neostigmine, sugammadex was faster in reversing NMB (P < .0001) and more likely to be associated with higher train-of-four ratio values at extubation (mean difference, 0.18; 95% confidence interval [CI], 0.14-0.22; P < .0001) and lower risk of postoperative residual curarization after extubation (odds ratio [OR], 0.05; 95% CI, 0.01-0.43; P = .0068). Compared to neostigmine, sugammadex was associated with a significantly lower likelihood of global AEs (OR, 0.47; 95% CI, 0.34-0.66; P < .0001), respiratory AEs (OR, 0.36; 95% CI, 0.14-0.95; P = .0386), cardiovascular AEs (OR, 0.23; 95% CI, 0.08-0.61; P = .0036), and postoperative weakness (OR, 0.45; 95% CI, 0.21-0.97; P = .0409). Sugammadex and neostigmine were associated with a similar likelihood of postoperative nausea and vomiting (OR, 1.23; 95% CI, 0.70-2.15; P = .4719), pain (OR, 1.06; 95% CI, 0.15-7.36; P = .9559), neurologic AEs (OR, 1.47; 95% CI, 0.52-4.17; P = .4699), general AEs (OR, 0.75; 95% CI, 0.47-1.21; P = .2448), and changes in laboratory tests' values (OR, 0.57; 95% CI, 0.18-1.78; P = .3368).ConclusionsResults from this meta-analysis suggest that sugammadex is superior to neostigmine, as it reverses NMB faster and more reliably, with a lower risk of AEs.     

Prostate cancer detection: The impact of obesity on Asian men

ObjectiveTo evaluate the impact of body mass index (BMI) on prostate cancer detection in biopsy-naive men presenting to a single tertiary hospital in Singapore.Materials and methodsWe retrospectively examined 458 men who underwent initial prostate biopsies between January 2012 and April 2014. Indications for biopsy were serum prostate-specific antigen level≥4.0 ng/ml, or digital rectal examination findings suspicious for malignancy, or both. Only men with serum prostate-specific antigen level <20 ng/ml were included. BMI categories were based on the World Health Organization recommendations (normal:<25.0, overweight: 25.0–29.9, and obese: ≥30).ResultsOf the 458 men included in our cohort, 125 (27.3%) men were positive for prostate cancer on biopsy, with 69 (15.1%) being clinically significant (Gleason≥7). Men with BMI≥25 kg/m² (41.7%) were younger (67.2 vs. 68.8 y, P = 0.030), had larger prostates (45.5 vs. 40.1 g, P = 0.014), and were more likely to have a positive biopsy finding (34.6% vs. 22.1%, P = 0.003). On multivariate analysis, being overweight or obese was associated with increased risk of having prostate cancer on biopsy (odds ratio [OR] = 2.61, 95% CI: 1.58–4.30, P<0.001 and OR = 3.26, 95% CI: 1.37–7.73 P = 0.007, respectively). The same trend was observed for clinically significant cancers but not for clinically insignificant cancers (OR = 3.57, 95% CI: 1.87–6.82, P<0.001 and OR = 3.86, 95% CI: 1.33–11.21, P = 0.013 for being overweight and obese, respectively).ConclusionAsian men with BMI≥25 kg/m² are at greater risk of having a positive initial biopsy result. The BMI threshold (BMI≥25 kg/m²) for Asian men to be at increased risk of prostate cancer detection on initial biopsy is lower than that of Western populations (BMI≥30 kg/m²).     

Prevalence and concordance of early and sustained remission assessed by various validated indices in the early arthritis “ESPOIR” cohort

ObjectivesTo assess the prevalence of remission in early arthritis, to evaluate the concordance across different criteria sets in defining this state, and to look for predictive factors for early and sustained remission.MethodsPatients from the ESPOIR cohort were followed-up every 6 months. We analysed early remission and sustained remission in 3 groups of patients: patients having rheumatoid arthritis (RA) according to 2010 ACR/EULAR criteria, undifferentiated arthritis (UA), and the whole cohort. Remission was defined according to ACR/EULAR criteria, 28 Joint Disease Activity Score (DAS28 < 2.6), and Simplified Disease Activity Index (SDAI ≤ 3.3). Agreement was evaluated by k-coefficient. Predictive factors for sustained remission at 1, 3 and 5 year in RA patients were analyzed.ResultsEight hundred and nineteen patients were included. Early remission rates in the RA/UA/ESPOIR groups were observed in respectively 29.2% (181/682), 51.4% (55/123) and 32.7% (239/813) of patients by DAS28; 15.7%, 29.1% and 18% by SDAI; and 11.2%, 29.1% and 12.8% by ACR/EULAR criteria. Agreement between classifications of remission was low for DAS28 vs. ACR/EULAR (k = 0.44), high for SDAI vs. ACR/EULAR (k = 0.78), and moderate for SDAI vs. DAS28 (k = 0.54). Lower baseline disease activity scores, non-menopausal status and younger age were the best predictive factors for sustained remission, with consistent results across the 3 definitions of remission.ConclusionOur study showed that the rate of early and sustained remission in early arthritis is dependent on the definition used, with a variable degree of agreement across criteria sets, but with consistent predictive factors of favourable outcome in patients finally diagnosed with RA.     

Instability of the extensor digitorum tendons in Jaccoud arthropathy assessed by semi-dynamic MRI of the metacarpophalangeal joints

PurposeThe purpose of this study was to test the hypothesis that Jaccoud arthropathy (JA) in patients with systemic lupus erythematosus (SLE) is associated with instability of the extensor digitorum (ED) tendons during flexion of the metacarpophalangeal (MCP) joints by comparing the position of the ED tendons between SLE patients with JA and control subjects on hand MRI obtained with flexed and extended MCP joints.Materials and methodsThirty-two hands of SLE patients with JA (13 women and 3 men; mean age, 50.0 ± 12.2 [SD] years; age range: 26–68 years) and 24 hands of sex- and age-matched control subjects (20 women and 4 men; mean age, 50.1 ± 13.0 [SD] years; age range: 24–68 years) were included in the study. Axial spin echo T1-weighted MRI images of the second to fifth MCP joints in flexion and in extension were obtained. Two radiologists (R1 and R2) separately measured the amplitude and assessed the direction of the displacement of the ED tendons with respect to the midline at the level of each MCP joint. Statistical analysis included two-way ANOVA with random effects to assess differences in amplitude and Fisher–Freeman–Halton exact test to assess differences in direction with P-values < 0.0083 and < 0.0063 considered as statistically significant respectively.ResultsAmplitude of the displacement of the ED tendons was statistically significantly greater in SLE patients with JA than in control subjects in flexion for both readers (median 58°, 95% confidence interval [CI]: 50°–65° vs. 20°, 95% CI: 16°–24°; P < 0.0001 for R1 and 54°, 95% CI: 47°–61° vs. 25°, 95% CI: 22°–28°; P < 0.0001 for R2) and in extension for one reader (17°, 95% CI: 15°–20° vs. 14°, 95% CI: 11°–16°; P = 0.0048 for R1 and 20°, 95% CI: 15°–25° vs. 16°, 95% CI: 12°–18°; P = 0.0292 for R2). Ulnar deviation of the ED tendons was statistically significantly more frequent in SLE patients with JA than in control subjects in flexion and in extension for both readers (P < 0.0001).ConclusionJA is associated with instability of the ED tendons in patients with SLE best depicted when MCP joints are flexed.     

Balloon Angioplasty as the Primary Treatment for Failing Infra-inguinal Vein Grafts

BackgroundWe sought to evaluate the role of balloon angioplasty as the primary modality in the management of vein graft stenoses.MethodsPatients who underwent infrainguinal vein graft bypass from January 2002 to December 2007 were enrolled into a surveillance program. Grafts which developed critical stenoses were identified and underwent urgent angiography with a view to angioplasty of the stenotic lesion. Lesions which were deemed unsuitable for angioplasty underwent urgent surgical repair.ResultsFour hundred and eleven grafts were followed up for a median of 19 months (range: 2–61). Ninety-six grafts (22.6%) developed critical stenosis. Twelve grafts occluded prior to repair and one was not intervened upon electively. Eight grafts underwent primary surgical repair. Seventy-six grafts underwent 99 endovascular procedures. Technical success was achieved in 60 grafts (78.9%). Of the grafts in which technical success had not been achieved, eight underwent repeat angioplasty and three were surgically repaired. Twenty-four grafts underwent repeat angioplasty for re-stenosis with a technical success rate of 71%. No difference was observed in graft patency (P = 0.08) or amputation rates (P = 0.32) between the grafts requiring intervention to maintain patency, and grafts which did not. Smoking [OR: 2.61 (95% CI: 1.51–4.53), (P = 0.006)], diabetes [OR: 2.55 (95% CI: 1.49–4.35), (P = 0.006)], renal failure [OR: 1.89 (95% CI: 1.19–3.38), (P = 0.040)] and recurrent stenosis [OR: 3.22 (95% CI: 1.63–4.69), (P < 0.001)] were risk factors for graft occlusion.ConclusionsBalloon angioplasty of failing infrainguinal vein bypass grafts is safe and can be performed with an acceptable medium term patency rate, albeit with a significant risk of re-stenosis which can be successfully treated in most patients using repeat endovascular intervention.     

Perioperative risks of narcolepsy in patients undergoing general anesthesia: A case-control study

Study objectiveTo compare the perioperative outcomes between patients with narcolepsy and matched controls undergoing anesthetic management.DesignRetrospective 2:1 matched study design.SettingLarge tertiary medical center.PatientsNarcoleptic patients who underwent general anesthesia from January 1, 2011, through September 30, 2015, were matched with controls by age, sex, and type and year of surgery.MeasurementsMedical records were reviewed for episodes of respiratory depression during phase I recovery and for other meaningful perioperative outcomes.Main resultsThe perioperative courses of 76 narcoleptic patients and their controls were examined. Compared to controls, narcoleptic patients were more often prescribed central nervous system stimulants (73.7% vs 4.0%, P < 0.001) and antidepressants (46.1% vs 27.6%, P = 0.007) and more often had obstructive sleep apnea (40.8% vs 19.1%, P < 0.001). The intraoperative course was similar. The number of episodes of respiratory depression was not different between patients and controls (5 [6.6%] vs 12 [7.9%], respectively; P = 0.80). Narcoleptic patients had a higher frequency of emergency response team activations (5 of 76 [6.6%]; 95% CI, 2.2%–14.7%) compared to controls (2 of 152 [1.3%]; 95% CI, 0.2%–4.7%) (P = 0.04). Hemodynamic instability was the indication for all emergency response team activations except 1, which was for a narcoleptic patient who had excessive postoperative sedation and respiratory depression.ConclusionsNarcoleptic patients had similar intraoperative courses as the matched controls, including phase I anesthetic recovery. However, they had a higher rate of emergency response team activations than the controls, which suggests that patients with narcolepsy may be at increased perioperative risk.     

Rheumatoid arthritis risk in periodontitis patients: A systematic review and meta-analysis

ObjectiveMany clinical studies have been carried out to investigate the relationship between periodontitis and rheumatoid arthritis (RA). Owing to limited evidence and inconsistent findings among these studies, it is unclear whether periodontitis would increase the risk for RA. This meta-analysis was performed to evaluate whether periodontitis represents a risk factor for RA.MethodsPubMed, Cochrane Library, Embase, Web of Science, and Wanfang were searched for eligible studies that compared periodontitis patients with controls. A pooled odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the association between periodontitis and RA.ResultsThirteen studies including a total of 706611 periodontitis patients and 349983 control subjects were included. The pooled OR of RA risk between periodontitis and controls was (OR: 1.69; 95% CI: 1.31–2.17; P < 0.0001), indicating that the patients in periodontitis group had a 69% greater risk for RA than people in control group. When stratified by disease type, the pooled results showed periodontitis represents a risk factor for incident RA (OR = 1.70, 95%CI: 0.75–3.85, P < 0.001) and mixed RA (OR = 1.61, 95%CI: 1.26–2.06; P < 0.001). When stratified by disease duration, the pooled results showed periodontitis represents a risk factor for RA disease duration > 5 years (OR = 2.88, 95%CI: 0.66–12.62, P = 0.018), disease duration < 5 years (OR = 2.59, 95%CI: 0.83–8.11, P < 0.001), mixed disease duration (OR = 1.53; 95%CI: 1.05–2.22, P < 0.001).ConclusionOur meta-analysis revealed an increased risk of RA in patients with periodontitis compared to healthy controls. Moreover, when stratified by disease type, there was a higher risk between incident RA and periodontitis. When stratified by disease duration, the patients with periodontitis might be more closely associated with the RA patients with disease duration >5 years.     

Associations between ocular and extra-ocular assessment in primary Sjögren's syndrome*

ObjectivesTo assess associations between ophthalmological features and the main systemic biomarkers of primary Sjögren's Syndrome (pSS), and to identify systemic biomarkers associated with severe keratoconjunctivitis sicca (KCS) in pSS patients.MethodsIn this cross-sectional study, data was retrospectively extracted from the monocentric cohort of the French reference centre for pSS. We analysed data from the initial visit of patients admitted for suspicion of pSS and included patients validating pSS ACR/EULAR classification criteria. Ophthalmological assessment included Schirmer's test, tear break-up time, ocular staining score (OSS), and visual analogue scale (DED-VAS) for dry eye disease (DED) symptoms. Results of minor salivary gland biopsy, unstimulated whole salivary flow rate, anti-SSA/Ro antibodies, anti-SSB/La antibodies, and rheumatoid factor (RF) were collected.ResultsA total of 253 patients (245 females) with confirmed pSS, aged 56.6 ± 13.0 years, were included, among which 37% had severe KCS. Multivariate analysis showed that the presence of anti-SSA/Ro antibodies, anti-SSB/La antibodies and RF were associated with conjunctival OSS (odds ratio–OR– = 1.25 per OSS unit increase; confidence interval–CI–95% = 1.05–1.49; P = 0.01; OR = 1.31 per OSS unit increase; CI95% = 1.09–1.58, P = 0.002, and OR = 1.34 per OSS unit increase; CI95% = 1.12–1.59; P = 0.001, respectively). Both anti-SSB/La antibodies and DED-VAS ≥ 5 were significantly associated with severe KCS (OR = 2.03; CI95% = 1.03–4.00; P < 0.05 and OR = 2.52, CI95% = 1.31–4.90; P < 0.01, respectively).ConclusionAssociation between conjunctival OSS and systemic biomarkers of pSS indicate the crucial importance of conjunctival staining when pSS is suspected as a cause of DED. Conversely, patients with anti-SSB and DED-VAS ≥ 5 features should be prioritized for extensive evaluation by an ophthalmologist due to their association with severe KCS.     

Effects of polymorphisms in TRAILR1 and TNFR1A on the response to anti-TNF therapies in patients with rheumatoid and psoriatic arthritis

ObjectivesAs the role of polymorphisms in death receptors (DRs) such as Tumor Necrosis Factor–related Apoptosis-inducing Ligand Receptor 1 (TRAIL-R1) and Tumor Necrosis Factor Receptor 1A (TNF-R1A) on the response to anti-TNF therapy remains unknown, we evaluated the association between TRAILR1 and TNFR1A gene polymorphisms (rs20575/C626G and rs767455/G36A) and the pharmacogenetics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with TNFα blockers.MethodsOne hundred and forty-five patients (90 RA and 55 PsA) treated with anti-TNFα therapy (RA: 75 infliximab, 8 etanercept, 7 adalimumab. PsA: 27 infliximab, 19 etanercept, 9 adalimumab) were genotyped for TRAILR1 and TNFR1A polymorphisms by allelic discrimination. The response to anti-TNFα was assessed by EULAR criteria.ResultsIn RA, the TRAILR1 CC genotype was associated with a better response after 3 and 6 months of anti-TNFα treatment (CC: 91.7% vs. CG/GG: 62.2%; P = 0.019, and CC: 82.6% vs. CG/GG: 56.1%; P = 0.019, respectively). Similar results were observed in only infliximab-treated RA patients. With respect to the TNFR1A polymorphism, there was an association between the AA genotype and a poorer response at 3 months in RA patients (AA: 39.3% vs. AG/GG: 19.0%; P = 0.04).In PsA, TRAILR1 CC genotype was only associated with EULAR response to infliximab at 6 months (CC: 71.4% vs CG/GG: 50%P = 0.048). In contrast to RA, the TNFR1 polymorphism in PsA was associated with a better response at 3 months (AA 88% vs AG/GG 58.9%; P = 0.04).ConclusionsThis study provides the first evidence that a polymorphism in TRAILR1 influences the response to anti-TNFα therapy in RA and also suggests that TNFR1A polymorphism may have opposing effects on the response to anti-TNFα in RA and PsA.     

Association between common risk factors and molecular subtypes in breast cancer patients

BackgroundBreast cancer is the most commonly diagnosed cancer in women worldwide and characterized its by molecular and clinical heterogeneity. Gene expression profiling studies have classified breast cancers into five subtypes: luminal A, luminal B, HER-2 overexpressing, basal-like, and normal breast-like. Although clinical differences between subtypes have been well described in the literature, etiologic heterogeneity have not been fully studied. The aim of this study was to assess the associations between several hormonal and nonhormonal risk factors and molecular subtypes of breast cancer.MethodsThis cross-sectional study consisted of 1884 invasive breast cancer cases. Variables studied included family history, age at first full-term pregnancy, number of children, duration of lactation, menstruation history, menopausal status, blood type, smoking, obesity, oral contraceptive use, hormone replacement therapy and in vitro fertilization. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariate logistic regression analysis.ResultsThousand two-hundred and forty nine patients had luminal A, 234 had luminal B, 169 had HER-2 overexpressing and 232 had triple negative breast cancer. The age of ≥40 years was found to be a risk factor for luminal A (OR 1.41 95% CI 1.15–1.74; p = 0.001) and HER-2 overexpressing subtype (OR: 1.51, 95% CI: 1.01–2.25; p = 0.04). Women who were nulliparous (OR 1.48, 95% CI 1.03–2.13; p = 0.03) or who had their first full-term pregnancy at age 30 years or older (OR 1.25 95% CI 0.83–1.88; p = 0.04) were at increased risk of luminal breast cancer, whereas women with more than two children had a decreased risk (OR 0.68, 95% CI 0.47–0.97; p = 0.03). Breast-feeding was also a protective factor for luminal subtype (OR 0.74, 95% CI 0.53–1.04; p = 0.04) when compared to non-luminal breast cancer. We found increased risks for postmenopausal women with HER-2 overexpressing (OR 2.20, 95% CI 0.93–5.17; p = 0.04) and luminal A (OR 1.87, 95% CI 0.93–3.90, p = 0.02) breast cancers, who used hormone replacement therapy for 5 years or more. Overweight and obesity significantly increased the risk of triple negative subtype (OR 1.89 95% CI 1.06–3.37; p = 0.04 and OR 1.90 95% CI 1.00–3.61; p = 0.03), on the contrary, decreased the risk of luminal breast cancer (OR 0.63 95% CI 0.43–0.95; p = 0.02 and OR 0.50 95% CI 0.32–0.76; p = 0.002, respectively) in premenopausal women. There were no significant differences between risk of breast cancer subtypes and early menarche, late menopause, family history, postmenopausal obesity, oral contraseptive use, smoking, in vitro fertilization, blood groups and use of hands.ConclusionsReproductive and hormonal characteristics (breastfeeding, parity, age at first full-term birth, hormone replacement therapy) were associated with luminal subtype, compared to non-luminal breast cancer, as consistent with previous studies. Obesity and overweight increased the risk of triple negative subtype, particularly in premenopausal women. Older age and use of hormone replacement therapy were related to the risk of HER-2 overexpressing breast cancer. Our data suggest a significant heterogeneity in association of traditional breast cancer risk factors and tumor subtypes.     

Prediction of overall survival in patients with hepatocellular carcinoma treated with Y-90 radioembolization by imaging response criteria

PurposeTo evaluate the potential of imaging criteria in predicting overall survival of patients with hepatocellular carcinoma (HCC) after a first transcatheter arterial yttrium-90 radioembolization (TARE)Materials and methodsFrom October 2013 to July 2017, 37 patients with HCC were retrospectively included. There were 34 men and 3 women with a mean age of 60.5 ± 10.2 (SD) years (range: 32.7–78.9 years). Twenty-five patients (68%) were Barcelona Clinic Liver Cancer (BCLC) C and 12 (32%) were BCLC B. Twenty-four primary index tumors (65%) were > 5 cm. Three radiologists evaluated tumor response on pre- and 4–7 months post-TARE magnetic resonance imaging or computed tomography examinations, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, modified RECIST (mRECIST), European Association for Study of the Liver (EASL), volumetric RECIST (vRECIST), quantitative EASL (qEASL) and the Liver Imaging Reporting and Data System treatment response algorithm. Kaplan–Meier survival curves were used to compare responders and non-responders for each criterion. Univariate and multivariate Cox proportional hazard ratio (HR) analysis were used to identify covariates associated with overall survival. Fleiss kappa test was used to assess interobserver agreement.ResultsAt multivariate analysis, RECIST 1.1 (HR: 0.26; 95% confidence interval [95% CI]: 0.09–0.75; P = 0.01), mRECIST (HR: 0.22; 95% CI: 0.08–0.59; P = 0.003), EASL (HR: 0.22; 95% CI: 0.07–0.63; P = 0.005), and qEASL (HR: 0.30; 95% CI: 0.12–0.80; P = 0.02) showed a significant difference in overall survival between responders and nonresponders. RECIST 1.1 had the highest interobserver reproducibility.ConclusionRECIST and mRECIST seem to be the best compromise between reproducibility and ability to predict overall survival in patients with HCC treated with TARE.     

Estudio prospectivo de los factores asociados al delirium en el postoperatorio de la cirugía abdominal urgente

IntroductionDelirium is a frequent complication in elderly patients after urgent abdominal surgery.MethodsProspective study of consecutive patients aged ≥ 65 years who had undergone urgent abdominal surgery from 2017-2019. The following variables were recorded: age, sex, ASA, physiological state, cognitive impairment, frailty (FRAIL Scale), functional dependence (Barthel Scale), quality of life (Euroqol-5D-VAS), nutritional status (MNA-SF), preoperative diagnosis, type of surgery (BUPA Classification), approach and diagnosis of postoperative delirium (Confusion Assessment Method). Univariate and multivariate analyses were performed to analyze the correlation of these variables with delirium.ResultsThe study includes 446 patients with a median age of 78 years, 63.6% were ASA ≥ III and 8% had prior cognitive impairment. 13.2% were frail and 5.4% of the patients had a severe or total degree of dependence. 13.6% developed delirium in the postoperative period. In the univariate analysis, all the variables were statistically significant except for sex, type of surgery (BUPA) and duration. In the multivariate analysis the associated factors were: age (P < .001; OR: 1,08; 95% CI: 1,038-1,139), ASA (P = .026; OR: 3.15; 95% CI: 1.149-8.668), physiological state (P < .001; OR: 5.8; 95% CI: 2.176-15.457), diagnosis (P = .006) and cognitive impairment (P < .001; OR: 5.8; 95% CI: 2.391-14.069).ConclusionThe factors associated with delirium are age, ASA, physiological state in the emergency room, preoperative diagnosis and prior cognitive impairment.     

Prospective cohort study of effects of infliximab on rheumatoid factor,anti-cyclic citrullinated peptide antibodies and antinuclear antibodies in patients with long-standing rheumatoid arthritis

BackgroundAntibodies to cyclic citrullinated peptide (anti-CCP) and IgM rheumatoid factor (IgM-RF) are well-established serological markers for rheumatoid arthritis (RA). Lupus-like disease with antinuclear antibodies (ANA) has been reported during TNFα antagonist therapy. Our objectives were to investigate the effect of infliximab therapy on these three autoantibodies in patients with established RA and to look for correlations linking IgM-RF and anti-CCP titres to a treatment response (defined as a good or moderate EULAR response) after 48 weeks of infliximab therapy.MethodsThirty-six patients with long-standing RA not responding to disease-modifying anti-rheumatic drugs (DMARDs) received intravenous infliximab (starting dose: 3 mg/kg) at 0, 2, and 6 weeks then at 8-week intervals, in combination with a DMARD. At baseline, week 24, and week 48, C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were determined and the disease activity score (DAS28) was calculated. Serum samples collected at the same time points were used to measure anti-CCP (commercial second-generation ELISA), IgM-RF (quantitative nephelometric assay), and ANA (indirect immunofluorescence in HEp2 cells). Correlations linking baseline autoantibody titres to changes in autoantibody levels were examined.ResultsAt baseline, tests were positive for anti-CCP in 31/36 (94.6%) patients, IgM-RF in 29/36 (80.5%) patients, and ANA in 16/36 (44%) patients. IgM-RF titres decreased significantly (p < 0.001), whereas anti-CCP showed little change (p = 0.053). ANA titres increased significantly (p < 0.001). The treatment response was not associated with changes in anti-CCP or IgM-RF titres during infliximab therapy (OR for a response in patients with a 50% anti-CCP decrease, 0.77 [95%CI, 0.16–3.58]; OR for a response in patients with a 50% IgM-RF decrease, 0.82 [95%CI, 0.16–4.13]).ConclusionsDuring infliximab therapy used to treat established RA, IgM-RF titres showed larger decreases than anti-CCP titres. Changes in IgM-RF and anti-CCP failed to correlate with the 48-week treatment response.     

Hiperlactatemia en la ablación quirúrgica de la fibrilación auricular y cirugía cardiaca. ¿Es un factor predictivo de morbimortalidad posoperatoria?

IntroductionIncreased serum lactate in postoperative cardiac surgery is very common and its pathogenesis is due to multiple factors. The elevation of serum lactate is associated with tissue hypoxia (hyperlactatemia type A) and non-hypoxic (hyperlactatemia type B) metabolic disorders. The aim of the study was to assess the evolution of postoperative lactate in surgical atrial fibrillation ablation during cardiac surgery, and to determine whether lactate levels could be predictors of morbimortality.Material and methodsA case-control study was conducted on 32 patients undergoing surgical atrial fibrillation ablation and cardiac surgery (Maze group) and 32 matched patients (Control group), operated on between 2011 and 2012. An analysis was made of the levels of postoperative lactate, perioperative morbimortality and hospital length of stay. A univariate and multivariate study was performed for a composite endpoint of morbimortality, and prolonged length of stay.ResultsLactate levels were significantly higher at 6, 12 and 24 h in the Maze group. The univariate analysis showed that being in the Maze group (OR 3.88; 95% CI 1.3-11.1; P = .01) and an elevated lactate at 12 h (OR 1.33; 95% CI 1.01-1.7; P = .04) were significant predictors of major complications, mortality, and longer hospital stays. In the multivariate analysis, surgical atrial fibrillation ablation (Maze group) was an independent predictor of major complications (OR 4.13; 95% CI 1.312.9; P = .015) for the morbimortality composite endpoint (OR 3.9; 95% CI 1.3-11.6; P = .01), and prolonged length of stay in the Intensive Care Unit (OR 5.7; 95% CI 2.01-15.7; P = .01).ConclusionsThe atrial fibrillation surgical ablation may be a not-yet-described cause of type B hyperlactatemia, with serum peak values being reached between 4-24 h after cardiac surgery. The predictive value of this elevation, its correlation with morbimortality, its sensitivity and specificity to discriminate the significant thresholds needs to be defined.     

An audit of the efficacy of a structured handover tool in obstetric anaesthesia

IntroductionThe SAFE handover tool was developed to reduce critical omissions during handovers in obstetric anaesthesia. It comprises a simple proforma onto which the outgoing team documents patients who fall into one of four anaesthetically relevant categories: Sick patients; At-risk patients (of emergency caesarean section, major haemorrhage or anaesthetic problems); Follow-ups; and Epidurals. We hypothesised that its use would reduce the number of critical omissions at handover.MethodsThe efficacy of the SAFE handover tool was assessed through several audit cycles in a single maternity unit. The four SAFE categories were considered the gold standard, since they encompassed the consensus opinion of senior obstetric anaesthetists with respect to parturients they most wanted to know about at handover. Against these criteria it was possible to compare the number of cases that should have been handed-over against the number that were actually handed-over.ResultsAfter implementation of the handover tool, patients were four times more likely to be handed-over than without the use of the tool: an increase from 49% to 79% of relevant cases (P < 0.0001, OR 4.1, 95% CI 2.19–7.6). The handover tool was particularly effective at increasing the handover rates of Sick and At-risk parturients, which increased from 21% to 67% (P < 0.0001, OR 7.7, 95% CI 2.7–21.7) and 25% to 78% (P < 0.01, OR 9.9, 95% CI 1.6–61.6), respectively.ConclusionThe SAFE handover tool significantly increased handover rates of anaesthetically relevant parturients. It is easy to remember and consistent with UK National Health Service Litigation Authority’s guidance on risk management in maternity units.