Effectiveness and safety of tocilizumab in patients with refractory or severe Takayasu's arteritis: A prospective cohort study in a Chinese population

ObjectiveTo assess the effectiveness and safety of tocilizumab (TCZ) in treating severe/refractory Takayasu's arteritis (TAK).MethodsA prospective cohort study was started on 1 November 2013 and terminated on 10 June 2020. Thirty-seven patients diagnosed as severe/refractory TAK, treated with TCZ combined with or without immunosuppressors were enrolled. Treatment response (complete remission (CR) and partial remission (PR)), imaging progression and side effects were analyzed at 6-month treatment. Disease flare was analyzed during the remaining follow-up.ResultsThe CR and RR rates were 70% and 88% at 6 months of TCZ treatment, respectively. Glucocorticoids was tapered from 30.0 (20.0–40.0) to 15.0 (10.0–15.0) mg/day at 6 months. Younger patients (≤ 26 years) (OR = 14.6, 95% CI 1.27–170.4, P < 0.05) and those with involvement of bilateral carotid arteries or vertebral arteries (OR = 14.6, 95% CI 1.27–169.1, P < 0.05) might show a better response to TCZ at 6 months. Combined therapy of immunosuppressors had no significant effects on the effectiveness of TCZ at 6 months. Among the total 23 patients with CR at 6 months, 14 cases discontinued TCZ therapy after 6 months, and disease flare was observed in six ones (43%), with medium flare at 7 (7–9.8) months. One patient (11%) who continued TCZ therapy suffered disease flare at 8 months. Infections were the most commonly observed side effects (38%), with four patients discontinuing TCZ treatment due to severe infections.ConclusionTCZ treatment achieved a favorable response with acceptable adverse effects for TAK.     

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.     

Predictors of response to anti-TNF therapy in RA patients with moderate or high DAS28 scores

ObjectivesTo identify the clinical factors predicting a good clinical response to anti-TNF therapy in rheumatoid arthritis (RA) patients entered in the LORHEN registry after 5 years of treatment with anti-TNF agents and divided into two groups on the basis of their baseline DAS28 scores (moderate > 3.2–5.1 [MDA] and high > 5.1 [HDA]).MethodsDisease activity at baseline and after 12 months was assessed using the DAS28, and response was evaluated using the EULAR improvement criteria.ResultsThe study involved 1300 patients with established RA: 975 with HDA and 325 with MDA. After a mean 36-month, 29.6% of the patients had a DAS28 score of less or equal to 2.6 (HDA 25.8% vs. MDA 43.0%; P < 0.001) and were considered to be in remission. A higher probability of a good EULAR response in patients with HDA was associated with male gender (F vs. M – OR 0.45, 95% CI 0.26–0.78; P: 0.004), lower age at the start of treatment (OR 0.98, 95% CI 0.96–0.99; P: 0.002), the absence of comorbidities (OR 0.18, 95% CI 0.06–0.52; P: 0.002) or no previous use of corticosteroids (OR 1.92, 95% CI 1.14–3.22; P: 0.015) and the use of adalimumab vs. infliximab (OR 2.21, 95% CI 1.37–3.57; P 0.001); in patients with MDA, the probability of a good EULAR response was associated with male gender (F vs. M – OR 0.39, 95% CI 0.17–0.90; P: 0.027).ConclusionsWith the exception of male gender, the factors predicting a good EULAR response are different in patients with MDA and those with HDA.     

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.     

Response to interleukin-6 receptor antagonists in patients with rheumatoid arthritis is independent of the number of prior used TNF inhibitors: A systematic review and metaanalysis

ObjectiveTo investigate whether early response to tocilizumab (TCZ) and sarilumab (SAR) therapy in patients with active rheumatoid arthritis (RA) is influenced by previous use of biologic agents.MethodsWe performed a systematic literature review and a meta-analysis of original studies that analyzed the effectiveness of TCZ or SRL in subgroups of RA patients, including biologic-naïve patients versus those with inadequate response to at least one biologic DMARD (bDMARD), and patients with failure to 1 versus ≥ 2 bDMARDs.ResultsThe study selection process finally included 17 articles corresponding to 14 studies, including 7 randomized controlled trials (RCTs). Although the existing literature that compared the response in biologic-naïve patients versus those with inadequate response to at least one bDMARD showed conflicting results, meta-analysis of 6 published studies revealed a significantly higher likelihood of remission (RR = 1.3; 95% CI: 1.2–1.5) and low activity disease (RR = 1.3; 95% CI: 1.2–1.4) in the biologic-naïve group at week 24. However, differences between groups were not clinically meaningful in all studies and not always maintained after 6 to 12 months of treatment. In addition, data from RCT RADIATE and TARGET suggest that the response to IL-6 pathway inhibitors seems to be similar, regardless of the number of tumor necrosis factor inhibitors (TNFis) previously tested.ConclusionDisease activity was more rapidly reduced in the early stages of treatment in biologic-naïve patients. However, near similar efficacy can be expected in patients who experienced a failure of at least one bDMARD (mainly TNFis) beyond the first 6 to 12 months of treatment, suggesting that the response occurs independently of the number of prior TNFis.     

Long-term Effect of CPAP Treatment on Cardiovascular Events in Patients With Resistant Hypertension and Sleep Apnea. Data From the HIPARCO-2 Study

BackgroundThere is some controversy about the effect of continuous positive airway pressure (CPAP) on the incidence of cardiovascular events (CVE). However, the incidence of CVE among patients with both obstructive sleep apnea (OSA) ans resistant hypertension (HR) has not been evaluated. Our objective was to analyze the long-term effect of CPAP treatment in patients with RH and OSA on the incidence of CVE.MethodsMulti-center, observational and prospective study of patients with moderate-severe OSA and RH. All the patients were followed up every 3?6 months and the CVE incidence was measured. Patients adherent to CPAP (at least 4 h/day) were compared with those with not adherent or those who had not been prescribed CPAP.ResultsValid data were obtained from 163 patients with 64 CVE incidents. Treatment with CPAP was offered to 82%. After 58 months of follow-up, 58.3% of patients were adherent to CPAP. Patients not adherent to CPAP presented a non-significant increase in the total CVE incidence (HR:1.6; 95%CI: 0.96?2.7; p = 0.07). A sensitivity analysis showed that patients not adherent to CPAP had a significant increase in the incidence of cerebrovascular events (HR: 3.1; CI95%: 1.07?15.1; p = 0.041) and hypertensive crises (HR: 5.1; CI95%: 2.2?11.6; p = 0.006), but the trend went in the opposite direction with respect to coronary events (HR: 0.22; CI95%: 0.05?1.02; p = 0.053).ConclusionsIn patients with RH and moderate-severe OSA, an uneffective treatment with CPAP showed a trend toward an increase in the incidence of CVE (particularly neurovascular events and hypertensive crises) without any changes with respect to coronary events.     

Factores influyentes en la respuesta al rescate con radioterapia tras prostatectomía radical

ObjectiveTo analyze the influential factors in the response in prostatectomized patients with subsequent biochemical relapse (BCR) and treated with salvage radiotherapy (RTP).Material and methodsWe analyzed 313 patients with pT2/pT3 prostate cancer who were receiving salvage therapy due to biochemical relapse (from a series of 1,310 radical prostatectomies between 1989-2012). Of the 313 patients; 159 (50.8%) only received androgen deprivation (AD), 63 (20.1%) Radiotherapy (RTP) plus concomitant AD and 91 (29.1%) only RTP. Of these, 57 (62.6%) have maintained complete response and 34 (37.4%) had failure response with post-RTP BCR.ResultsStudy of the group treated exclusively with salvage RTP. Ninety-one patients were treated with salvage RTP. Median follow-up was 6.4 years and median to recurrence 11 months. Post-RTP biochemical relapse-free survival (PRBRFS) was 68 ± 7% and 30 ± 10% in 5 to 10 years. Median PRBRFS was 7.3 years (6.3-8.3). Initial PSA (HR: 1.08; 95% CI: 1.01-1.1 P = .02) with best PSA cut-off point PSA > 20 ng/ml (HR: 13.6; 95% CI: 2.1-86 P = .005) and PSA pre-RTP (HR: 1.9; 95% CI: 1.2-3.3; P = .009), best PSA cut-off point PSA preRTP 0.92 ng/ml (HR: 4.5; 95% CI: 1.3-15.6; P = .01) showed independent influence in the response in the multivariate study. PRBRFS at 5 years, 81 ± 9% versus 58 ± 9% with initial PSA < 20 or > 20 ng/ml (P = .03). PRBRFS at 5 years, 93 ± 5% versus 53 ± 10% according to PSA pre-RTP < 0.9 or > 0.9 ng/ml (P = .02).ConclusionsIn patients treated with salvage RTP after radical prostatectomy, the preoperative PSA > 20 ng/ml and PSA preRTP > 0.92 ng/ml shows an independent influence on the response.     

A genetic association study of the CLEC12A gene in rheumatoid arthritis

ObjectiveThe CLEC12A gene codes for an immune inhibitory receptor that maps to 12p13.2. Since an increase in CLEC12A mRNA correlates with rheumatoid factor values greater than 40 IU/ml in rheumatoid fibroblast-like synovial cells, this study assessed the potential of an association between CLEC12A and rheumatoid arthritis (RA) using a phenotype-based approach.MethodsA discovery cohort of Western European ethnicity was genotyped for eight tag single nucleotide polymorphisms. Statistical analyses relied on the transmission disequilibrium test, relative risk and 95% confidence interval (CI) calculations. Observed haplotype frequencies were compared to expected frequencies using a family-based association test. Statistically significant associations were further tested in a second cohort of unrelated West-European RA patients.ResultsAn overtransmission of the C allele of the rs1323461 tag single nucleotide polymorphism was observed (56.6% of allele C transmission, P = 0.046) in the discovery cohort. The relative risk of the AC and CC genotypes when compared to the AA genotype was high (relative risk = 4.08; 95% CI: 1.52–10.95, uncorrected P = 2.1 × 10^?3), particularly in the subgroup of erosive RA (relative risk = 5.27; 95% CI: 1.53–18.19, uncorrected P = 2.1 × 10^?3), both remaining statistically significant after conservative Bonferroni's correction. The CGAGCCGA haplotype was observed more frequently than expected (P = 0.013). In the second cohort, the C allele had a tendency to be more frequent in RA patients (82.4%) than controls (79.2%) (P = 0.069).ConclusionWe report a potential genetic association of CLEC12A with RA. Since CLEC12A encodes for the myeloid inhibitory C-type lectin-like receptor that modulates cytokine synthesis, this receptor may contribute to the pathogenesis of RA.     

Impacto de la expresión de p53, MIB-1 y PECAM-1 en el pronóstico del carcinoma urotelial de la pelvis renal

ObjectiveDetermine whether the overexpression p53, MIB-1 and PECAM-1 of protein levels is of interest in predicting the prognosis of transitional cell carcinoma of the upper urinary tract (TCC-UUT) with the primary seat in the renal pelvis.Material and methodA univariate and multivariate analysis was conducted for prognosis prediction in a series of 82 patients with TCC-UUT of the renal pelvis who had no metastases at diagnosis (N0/Nx M0) and were treated exclusively with nephroureterectomy. We assessed clinicopathological parameters (age, gender, tumor grade and extent, histological variety, growth pattern, vascular invasion, infiltration of the renal parenchyma, tumor necrosis) and the immunohistochemical expression of p53, MIB-1 (ki-67) and PECAM-1 (CD31) in sections performed with tissue microarray (TMA).ResultsA total of 47.6% of the patients had high-grade lesions according to the USIP-WHO classification. The growth pattern was flat in 15.85%. The distribution by T category was: 3.7% pTa, 51.2% pT1, 11% pT2, 29.3% pT3 and 4.9% pT4. The mean follow-up was 46.8+38.5 (range, 4-172) months. The median survival was reached at 57 (95% CI 44-63) months. The univariate analysis revealed that survival in these patients is associated with tumor size (P = .028), histological variety (P < .0001), growth pattern (P < .0001), grade (P < .0001), pT (P = .01), vascular invasion (P = .025), necrosis (P = .004) and overexpression of p53 (P = .0006), PECAM-1 (P = .0036) and MIB-1 (P = .0038). The Cox regression model showed that high-grade (HR, 4.2; 95% CI 1.28-13.79; P = .018), flat growth pattern (HR, 2.52; 95% CI 1.05-6.03; P = .038) and p53 overexpression (HR, 2.8; 95% CI 1.22-6.44; P = .015) were independent predictors.ConclusionHistological grade, tumor growth pattern and p53 overexpression were established as the primary predictors of prognosis for primary TCC-UUT of the renal pelvis. The independent value of MIB-1 observed in other studies was not reproduced in this study.     

Basal metabolic rate and Charlson Comorbidity Index are independent predictors of metabolic syndrome in patients with rheumatoid arthritis

ObjectiveTo prospectively analyze predictors of metabolic syndrome (MetS) in patients with rheumatoid arthritis (RA) during 2 years of follow-up.MethodsWe recruited 319 consecutive patients with RA who did not have MetS. MetS was defined in accordance with the modified National Cholesterol Education Program/Adult Treatment Panel III 2005 for Asian populations. Sociodemographic data, laboratory findings, disease activity data, and medication history were collected during face-to-face interviews at baseline and follow-up. Independent predictors of MetS were assessed by univariate and multivariate logistic regression analyses.ResultsOf the 247 patients with RA who completed the 2-year follow-up, 37 (15.0%) developed MetS. At baseline, these patients were older and had higher body mass index, waist circumference, waist-hip ratio, skeletal muscle mass, body fat mass, percent body fat, and Charlson Comorbidity Index scores, as well as lower basal metabolic rate (BMR). Moreover, these patients with MetS took less hydroxychloroquine and more oral hypoglycemic agents; they also had lower European Quality of Life Health-state Questionnaire scores. After exclusion of variables associated with MetS composition, multivariate analysis identified BMR (odds ratio [OR] = 0.205, 95% confidence interval [CI]: 0.078–0.541, P = 0.001) and Charlson Comorbidity Index score (OR = 2.191, 95% CI: 1.280–3.751, P = 0.004) as significant predictors of MetS.ConclusionsOur study showed that the annual incidence rate of MetS was 11.5% in patients with RA. Moreover, the development of MetS was associated with BMR and Charlson Comorbidity Index score at baseline.     

Diagnosis of postoperative recurrence of Crohn disease with MR-enterography: Value of diffusion-weighted imaging

PurposeTo compare the diagnostic capabilities of MR enterography (MRE) using contrast-enhanced (CE) sequences with those of MRE using diffusion-weighted (DW) imaging for the diagnosis of postoperative recurrence at the neo-terminal ileum and/or anastomosis after ileocolonic resection in patients with Crohn disease (CD), and to clarify the role of additional DW imaging to CE-MRE in this context.Material and methodsForty patients who underwent ileal resection for CD, and both endoscopy and MRE within the first year after surgery were included. There were 21 men and 19 women, with a mean age of 38 years ± 12 (SD) years (range: 18–67 years). MRE examinations were blindly analyzed independently by one senior (R1) and one junior (R2) radiologist for the presence of small bowel postoperative recurrence at the anastomotic site. During a first reading session, T2-, steady-state- and DW-MRE were reviewed (DW-MRE or set 1). During a separate distant session, T2-, steady-state- and CE-MRE were reviewed (CE-MRE or set 2). Lastly, all sequences were analyzed altogether (set 3). Performances of each reader for the diagnosis of postoperative recurrence were evaluated using endoscopic findings as the standard of reference (Rutgeerts score ≥ i2b).ResultsFifteen patients out of 40 (37.5%) had endoscopic postoperative recurrence at the anastomotic site. Sensitivity for the diagnosis of postoperative recurrence was 73% (95% CI: 51–96%) for R1 and 67% (95% CI: 43–91%) for R2 using set 1, and 80% (95% CI: 60–100%) for both readers using set 2. There was no significant differences in sensitivity between reading set 1 and reading set 2, for either R1 or R2 (R1, P  > 0.99; R2, P = 0.48). Specificity was 96% (95% CI: 88–100%) for both readers using set 1 or using set 2. Reading set 3 yielded an area under the ROC curve (AUC) of 0.93 (95% CI: 0.84–1) versus 0.89 (95% CI: 0.75–1) with set 1 (P = 0.18) and versus 0.89 (95% CI: 0.78–1) with set 2 (P = 0.21). No significant differences in AUC were found between set 1 or 2 and set 3 (P = 0.18), nor between set 1 and 2 (P = 0.76). Accuracies were 88% (95% CI: 74–95%) and 85% (95% CI: 71–93%) for DW-MRE for R1 and R2, respectively; 90% (95% CI: 77–96%) for CE-MRE for both readers; and 93% (95% CI: 80–97%) and 88% (95% CI: 74–95%) for R1 and R2 with set 3, respectively.ConclusionDW-MRE has diagnostic capabilities similar to those of CE-MRE for the diagnosis of postoperative recurrence of CD at the anastomotic site.     

La obesidad,la hipertensión y la diabetes mellitus afectan la tasa de complicaciones de las diferentes técnicas de nefrectomía

IntroductionTo investigate whether obesity, hypertension, and diabetes mellitus (DM) would increase post-nephrectomy complication rates using standardized classification method.MethodsWe retrospectively included 843 patients from March 2006 to November 2012, of whom 613 underwent radical nephrectomy (RN) and 229 had partial nephrectomy (PN). Modified Clavien classification system was applied to quantify complication severity of nephrectomy. Fisher's exact or chi-square test was used to assess the relationship between complication rates and obesity, hypertension, as well as DM.ResultsThe prevalence of obesity, hypertension, and DM was 11.51%, 30.84%, 8.78%, respectively. The overall complication rate was 19.31%, 30.04%, 35.71% and 36.36% for laparoscopic radical nephrectomy (LRN), open-RN, LPN and open-PN respectively. An increasing trend of low grade complication rate as BMI increased was observed in LRN (P = .027) and open-RN (P < .001). Obese patients had greater chance to have low grade complications in LRN (OR = 4.471; 95% CI: 1.290-17.422; P = 0.031) and open-RN (OR = 2.448; 95% CI: 1.703-3.518; P < .001). Patients with hypertension were more likely to have low grade complications, especially grade ii complications in open-RN (OR = 1.526; 95% CI: 1.055-2.206; P = .026) and open PN (OR = 2.032; 95% CI: 1.199-3.443; P = .009). DM was also associated with higher grade i complication rate in open-RN (OR = 2.490; 95% CI: 331-4.657; P = .016) and open-PN (OR = 4.425; 95% CI: 1.815-10.791; P = .013). High grade complication rates were similar in comparison.ConclusionsObesity, hypertension, and DM were closely associated with increased post-nephrectomy complication rates, mainly low grade complications.     

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.     

Management of bone fragility in patients with rheumatoid arthritis in France: An analysis of a national health insurance claims database

ObjectivesRheumatoid arthritis (RA) is considered a major risk factor for fragility fractures. We examined the quality of management of bone fragility in RA patients in a real-life setting.MethodsWe performed a longitudinal case-control retrospective study in a 1/97th random sample of French health care claims database from 2014 to 2016 to determine the extent of bone fragility management in patients with RA compared with non-RA matched controls.ResultsCompared to their non-RA controls (n = 4652), RA patients (n = 1008; mean age: 61.1 years; methotrexate: 69.7%; other conventional disease-modifying antirheumatic drugs (cDMARDs): 26.8%; biologic: 26.0%; corticosteroids: 36.9%) had more reimbursements for bone mineral density (BMD) measurements (21.6 vs. 9.2%; OR = 2.7 [2.3; 3.3]; P < 0.01) and for bisphosphonates (7.1 vs. 3.6%, OR = 2.0 [1.5; 2.7]; P < 0.05). In patients exposed to corticosteroids, RA patients underwent more BMD assessments than non-RA controls (28.0 vs. 18.8%; OR = 1.7 [1.3; 2.2]; P < 0.05). RA patients exposed to corticosteroids were more likely to sustain fracture than non-exposed RA patients (5.7 vs. 2.4%, P < 0.01). In addition, only when comparing patients exposed to corticosteroids, was there statistical evidence of an association between RA and an increased fracture rate (6.2 vs. 3.5%, P < 0.05).ConclusionPatients with RA exposed to corticosteroids are at high risk of fracture. Patients with RA had more bone fragility management than controls.     

Candidates to salvage therapy after external-beam radiotherapy of prostate cancer: Predictors of local recurrence volume and metastasis-free survival

PurposeThe purpose of this study was to assess the predictors of metastasis-free survival (MFS) and of the volume of the local recurrence in patients with rising prostate-specific antigen (PSA) serum level after radiotherapy for prostate cancer and referred for prostate magnetic resonance imaging (MRI) and biopsy in view of salvage treatment.Materials and methodsA total of 132 consecutive men (median age, 70 years; IQR, 66–77 years) with rising PSA after prostate radiotherapy who underwent prostate MRI and biopsy in view of salvage treatment between January 2010 and July 2017 were retrospectively evaluated at a single center. MFS predictors were assessed with Cox models. Predictors of the volume of the local recurrence (number of invaded prostate sectors at biopsy) were assessed using Poisson regression among variables available at PSA relapse.ResultsAt multivariate analysis, an initial Gleason score ≥ 8 (OR = 7 [95% confidence interval (CI): 1.2–40]; P = 0.03), a recent radiotherapy (OR = 17 [95% CI: 3.9–72]; P < 0.0001), the use of androgen deprivation therapy at PSA relapse (OR = 12.5 [95% CI: 2.8–57]; P = 0.001) and the number of invaded prostate sectors (OR = 1.5 [95% CI: 1.1–2]; P = 0.007) and maximum cancer core length (OR = 0.7 [95%CI: 0.6–0.9]; P = 0.002) at biopsy performed at PSA relapse were significant MFS predictors. The PSA level at relapse was significant independent predictor of the volume of local recurrence only when used as a continuous variable (P = 0.0002) but not when dichotomized using the nadir + 2 threshold (P = 0.41).ConclusionPathological and clinical factors can help predict MFS in patients with rising PSA after prostate radiotherapy and candidates to salvage treatment. The PSA level at relapse has strong influence on the local recurrence volume when used as a continuous variable.     

MRI combined with PSA density in detecting clinically significant prostate cancer in patients with PSA serum levels of 4∼10 ng/mL: Biparametric versus multiparametric MRI

PurposeTo compare the performance of biparametric magnetic resonance imaging (bpMRI) to that of multiparametric MRI (mpMRI) in combination with prostate-specific antigen density (PSAD) in detecting clinically significant prostate cancer (csPCa) in patients with PSA serum levels of 4∼10 ng/mL.Materials and methodsA total of 123 men (mean age, 66.3 ± 8.9 [SD]; range: 42–83 years) with PSA serum levels of 4∼10 ng/mL with suspected csPCa were included. All patients underwent mpMRI at 3 Tesla and transrectal ultrasound-guided prostate biopsy in their clinical workup and were followed-up for >1 year when no csPCa was found at initial biopsy. The mpMRI images were reinterpreted according to the Prostate Imaging Reporting and Data System (PI-RADS, v2.1) twice in two different sessions using either mpMRI sequences or bpMRI sequences. The patients were divided into 2 groups according to whether csPCa was detected. The PI-RADS (mpMRI or bpMRI) categories and PSAD were used in combination to detect csPCa. Receiver operating characteristic (ROC) curve and decision curve analyses were performed to compare the efficacy of the different models (mpMRI, bpMRI, PSAD, mpMRI + PSAD and bpMRI + PSAD).ResultsThirty-seven patients (30.1%, 37/123) had csPCa. ROC analysis showed that bpMRI (AUC = 0.884 [95% confidence interval (CI): 0.814–0.935]) outperformed mpMRI (AUC = 0.867 [95% CI: 0.794–0.921]) (P = 0.035) and that bpMRI and mpMRI performed better than PSAD (0.682 [95% CI: 0.592–0.763]) in detecting csPCa; bpMRI + PSAD (AUC = 0.907 [95% CI: 0.841–0.952]) performed similarly to mpMRI + PSAD (AUC = 0.896 [95% CI: 0.828–0.944]) (P = 0.151) and bpMRI (P = 0.224). The sensitivity and specificity were 81.1% (95% CI: 64.8–92.0%) and 88.4% (95% CI: 79.7–94.3%), respectively for bpMRI, and 83.8% (95% CI: 68.0–93.8%) and 80.2% (95% CI: 70.2–88.0%), respectively for mpMRI (P > 0.999 for sensitivity and P = 0.016 for specificity). Among the 5 decision models, the decision curve analysis showed that all models (except for PSAD) achieved a high net benefit.ConclusionIn patients with PSA serum levels of 4∼10 ng/mL, bpMRI and bpMRI combined with PSAD achieve better performance than mpMRI in detecting csPCa; bpMRI has a higher specificity than mpMRI, which could decrease unnecessary biopsy, and may serve as a potential alternative to mpMRI to optimize clinical workup.     

Bone turnover markers as predictive indicators of outcome in patients with breast cancer and bone metastases treated with bisphosphonates: Results from a 2-year multicentre observational study (ZOMAR study)

BackgroundWe evaluated the evolution and predictive value of bone turnover markers (BTMs) and circulating tumor cells (CTCs) with respect to mortality, disease progression (DP) and skeletal-related events (SREs), in patients with bone metastatic breast cancer (BmBCa). The correlation between BTMs and CTCs was also studied.MethodsIn a 2-year observational, multicenter study, the levels of three BTMs (N- and C-terminal telopeptides of collagen I [NTX and αα-CTX], and bone-specific alkaline phosphatase [BSAP]) and CTCs were analyzed every three months. Patients received zoledronic acid (4 mg every 28 days) from the baseline visit.Results234 patients were analyzed. The levels of the BTMs were increased at baseline and significantly decreased after 3 months (P < 0.05). In the Cox regression univariate analyses significant hazard ratios (HRs) for death were found for pathological BSAP values at baseline (5.03 [95% CI: 1.214–20.839; P = 0.0259]) and at 3 months (3.41 [95% CI: 1.367–8.498; P = 0.0085]). HRs > 2 were found for increased baseline and 3-month levels of NTX and CTC (P < 0.05). Only increased baseline BSAP levels were associated with DP (HR = 2.25 [95% CI: 1.391–3.626; P = 0.0009]). No biomarker was associated with SREs. In the multivariate analysis, pathologic levels at 3 months of NTX and BSAP were significantly associated with mortality (HRs = 3.59 [95% CI: 1.375–9.382; P = 0.0091] and 3.25 [95% CI: 1.293–8.189; P = 0.0120], respectively). CTC and BSAP were correlated during all study timepoints (P < 0.05).ConclusionsBaseline levels of NTX, BSAP and CTCs, and changes after treatment initiation with bisphosphonates, may be useful for the prognostic assessment of patients with BmBCa. BSAP showed the strongest prognostic value.     

Endovascular stenting for chronic femoro-iliac venous obstructive disease: Clinical efficacy and short-term outcomes

PurposeTo report the clinical efficacy and mid-term outcomes of endovascular treatment in patients with chronic, symptomatic, post-thrombotic femoro-iliac venous obstruction.Materials and methodsForty-two patients with post-thrombotic syndrome (PTS) presenting with femoro-iliac venous obstructive lesions treated in our institution by endovascular approach between March 2012 and October 2017 were retrospectively included. There were 27 women and 15 men with a mean age of 47.3 ± 17 (SD) years (range: 22–86 years). Procedure included first venous recanalization, then pre-dilatation and self-expandable metallic stenting of the narrowed or occluded iliac and/or femoral veins. Severity of PTS and quality of life were assessed at baseline and 3 months after the intervention respectively, using Villalta score and Chronic Venous Insufficiency Questionnaire (CIVIQ-20) scale. Imaging follow-up evaluation of stent patency was based on the results of duplex Doppler ultrasound and computed tomography.ResultsImmediate technical success was achieved in 41/42 (97.6%) patients, without any major complications. Primary patency, primary assisted patency and secondary patency at the end of the median imaging follow-up of 18.1 months (IQR, 9.7–34.4) were achieved in 29/42 (66.7%) patients, 33/42 (78.6%) patients and 37/42 (88.1%) patients, respectively. Median Villalta and CIVIQ-20 scores decreased from 14 (IQR, 10–19) and 57 (IQR, 39–72) at baseline, respectively, to 5 (IQR, 2–9) and 30 (IQR, 24–50) 3 months after the procedure, respectively (P < 0.0001), showing significant decrease in the severity of PTS and improvement in the quality of life. The multiple linear regression model showed that both baseline Villalta and CIVIQ-20 scores ([95% CI: −7.80–3.79; P < 0.0001] and [95% CI: 0.07–0.20; P < 0.0001], respectively), age (95% CI: 0.04–0.19; P = 0.002) and stenting expanse (95% CI: 0.97–5.65; P = 0.006) were independent variables related to Villalta gain. Baseline Villalta (95% CI: 0.89–2.23; P < 0.0001) was the single independent variable related to CIVIQ-20 gain.ConclusionThis study confirms the high clinical efficacy and favorable mid-term outcomes of endovascular stenting in patients with chronic symptomatic femoro-iliac venous obstructive lesions.     

Perioperative Red Blood Cell Transfusion and Outcome in Stable Patients after Elective Major Vascular Surgery

ObjectivesDefinitive evidence that red blood cell transfusion improves outcome after vascular surgery is lacking. The aims of the study were to determine, among stable consecutive patients who underwent elective major vascular surgery, (1) the association between postoperative transfusion and 30-day death, myocardial infarction, and both, and (2) and if this association differs according to the presence of postoperative anaemia (haemoglobin value less than 9.0 g/dL within 7 days after surgery).MethodsA retrospective observational study was conducted on 359 patients prospectively screened according to the ACC/AHA guidelines for preoperative risk in non-cardiac surgery. Main outcome was 30-day death; secondary outcomes 30-day myocardial infarction, and composite of 30-day myocardial infarction or death.ResultsOf the patients included, 95 (26.5%) received at least one unit of red blood cells. Patients who received transfusion had a significantly increased hazard of 30-day death (hazard ratio [HR] 11.72, 95% confidence interval [CI] 3.92–35.10; p < 0.0001), myocardial infarction (HR 3.3, 95% CI 1.7–6.1; p = 0.0003), and both (HR 4.0 95% CI 2.2–7.3; p < 0.0001). Such associations held even after adjusting for baseline characteristics, surgical risk, bleeding, and propensity to receive transfusion. There was a significant interaction between transfusion and postoperative anaemia (p = 0.012). In patients without anaemia, transfusion was associated with higher risk of 30-day death (HR 19.20, 95% CI 3.99–92.45; p = 0.007), myocardial infarction (HR 5.05, 95% CI 2.23–11.44; p = 0.0001), and both. Conversely, in patients with anaemia this association was not significant.ConclusionsIn patients who underwent elective major vascular surgery, perioperative transfusion was associated with a significantly increased risk of 30-day events which was more attributable to patients with lesser degree of anaemia. Our data caution against the use of liberal transfusion in stable vascular surgery patients.     

Burn induced nervous system morbidity among burn and non-burn trauma patients compared with non-injured people

ObjectiveBurns cause acute damage to the peripheral nervous system with published reports identifying that neurological changes after injury remain for a prolonged period. To shed some light on potential mechanisms, we assessed injury etiology and patterns of nervous system morbidity after injury by comparing long-term hospital admissions data of burns patients and other non-burn trauma patients with uninjured people.MethodsLinked hospital and death data of a burn patient cohort (n = 30,997) in Western Australia during the period 1980–2012 were analysed along with two age and gender frequency matched comparison cohorts: non-burn trauma patients (n = 28,647) and; non-injured people (n = 123,399). The number of annual NS disease admissions and length of stay (LOS) were used as outcome measures. Multivariable negative binomial regression modelling was used to derive adjusted incidence rate ratios and 95% confidence intervals (IRR, 95% CI) and adjusted Cox regression models and hazard ratios (HR) were used to examine time to first nervous system admission after burn and incident admission rates.ResultsThe most common peripheral nervous system condition identified in each cohort (burn, non-burn trauma, uninjured) were episodic and paroxysmal disorders followed by nerve root and plexus disorders and polyneuropathies/peripheral NS conditions. Significantly elevated admission rates for NS conditions (IRR, 95% CI) were found for the burn (2.20, 1.86–2.61) and non-burn trauma (1.85, 1.51–2.27), compared to uninjured. Peripheral nervous system admission rates after injury (IRR, 95% CI) were significantly higher regardless of age at time of injury for the burn (<15years: 1.97, 1.49–2.61; 15–45: 2.70, 2.016–3.55; ≥45 year: 1.62, 1.33–1.97) and non-burn trauma cohorts (<15years: 1.91, 1.55–2.35; 15–45: 1.94, 1.51–2.49; ≥45 year: 1.42, 1.18–1.72), when compared to the uninjured. Significantly higher rates of incident NS hospitalisations were found for the burn cohort vs. uninjured cohort for a period of 15-years after discharge (0–5 years: HR, 95% CI: 1.97, 1.75–2.22; 5–15 years; HR, 95% CI: 1.44, 1.28–1.63). The non-burn trauma cohort had significantly higher incident nervous system admissions for 10 years after discharge (0–30 days: HR, 95% CI: 4.75, 2.44–9.23; 30 days to 1-year HR, 95% CI: 2.95, 2.34–3.74; 1–5 years; HR, 95% CI: 1.47, 1.26–1.70; 5–10 years; HR, 95% CI: 1.34, 1.13–1.58).ConclusionsResults suggest that injury patients are at increased risk of peripheral nervous system morbidity after discharge for a prolonged period of time. The time patterns associated with incident nervous system conditions suggest possible differences in underlying pathology and long-term patient care needs. Further research is needed to elucidate the underlying neuropathology.