High prevalence of orofacial pain in juvenile fibromyalgia as detected by a novel tool specifically devised for children and adolescents.

OBJECTIVES: To examine the prevalence of temporomandibular disorders (TMD) in patients with juvenile fibromyalgia syndrome (JFS) and identify TMD characteristics specifically associated to JFS. METHODS: Signs and symptoms of TMD were assessed using a novel clinical tool specifically devised for children that consists of: 1. a self-report multiple-choice questionnaire; 2. a protocol for the clinical examination of the orofacial region. Multivariate logistic regression model was used to identify TMD features associated with JFS. RESULTS: Thirty JFS patients (median age 15.5 years) and 45 healthy controls (median age 15.0 years) were included in this cross-sectional study. Orofacial pain was reported by 26 of 30 JFS patients (86.7%) and by 3 of 45 controls (6.7%; p<0.001). Pain on TMJ palpation was present in 18 of 30 JFS patients (60%) and in 5 of 45 controls (11.1%; p<0.001). Median values of maximum spontaneous mouth opening, voluntary active opening and assisted passive opening were significantly higher in JFS patients than in controls. On multiple regression analysis spontaneous orofacial pain (OR: 21.0; p=0.005), diffuse tenderness on palpation of the masticatory muscles (OR: 14.9; p=0.026) and TMJ hypermobility (OR 1.42; p=0.008) were independently associated with JFS. CONCLUSIONS: The high prevalence of TMD in JFS highlights the need for a broader interdisciplinary evaluation of JFS patients. TMJ hypermobility, in addition to orofacial and masticatory muscle pain, is an important clue for the diagnosis of TMD in adolescents with JFS. Elucidating the link between these disorders will advance individualised management and improve treatment efficacy.

Procalcitonin for the diagnosis of postoperative bacterial infection after adult cardiac surgery: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Patients undergoing cardiac surgery are subject to infectious complications that adversely affect outcomes. Rapid identification is essential for adequate treatment. Procalcitonin (PCT) is a noninvasive blood test that could serve this purpose, however its validity in the cardiac surgery population is still debated. We therefore performed a systematic review and meta-analysis to estimate the accuracy of PCT for the diagnosis of postoperative bacterial infection after cardiac surgery. METHODS: We included studies on adult cardiac surgery patients, providing estimates of test accuracy. Search was performed on PubMed, EmBase and WebOfScience on April 12th, 2023 and rerun on September 15th, 2023, limited to the last 10 years. Study quality was assessed with the QUADAS-2 tool. The pooled measures of performance and diagnostic accuracy, and corresponding 95% Confidence Intervals (CI), were calculated using a bivariate regression model. Due to the variation in reported thresholds, we used a multiple-thresholds within a study random effects model for meta-analysis (diagmeta R-package). RESULTS: Eleven studies were included in the systematic review, and 10 (2984 patients) in the meta-analysis. All studies were single-center with observational design, five of which with retrospective data collection. Quality assessment highlighted various issues, mainly concerning lack of prespecified thresholds for the index test in all studies. Results of bivariate model analysis using multiple thresholds within a study identified the optimal threshold at 3 ng/mL, with a mean sensitivity of 0.67 (0.47-0.82), mean specificity of 0.73 (95% CI 0.65-0.79), and AUC of 0.75 (IC95% 0.29-0.95). Given its importance for practice, we also evaluated PCT's predictive capability. We found that positive predictive value is at most close to 50%, also with a high prevalence (30%), and the negative predictive value was always > 90% when prevalence was < 20%. CONCLUSIONS: These results suggest that PCT may be used to help rule out infection after cardiac surgery. The optimal threshold of 3 ng/mL identified in this work should be confirmed with large, well-designed randomized trials that evaluate the test's impact on health outcomes and on the use of antibiotic therapy. PROSPERO Registration number CRD42023415773. Registered 22 April 2023.

Diagnostic effectiveness of [18F]Fluoroestradiol PET/CT in oestrogen receptor-positive breast cancer: the key role of histopathology. Evidence from an international multicentre prospective study.

INTRODUCTION: [18F]Fluoroestradiol ([18F]FES) PET/CT has been proposed as a tool for detecting the oestrogen receptor density in patients with metastatic breast cancer (BC) non-invasively across all disease localizations. However, its diagnostic potential in terms of the detection rate (DR) of metastases is unclear. In this study, we pitted this method against [18F]FDG PET/CT and tried to identify predictors of the diagnostic superiority of the [18F] FES-based method. MATERIALS AND METHODS: From a multicentre database, we enrolled all patients with metastatic BC who had undergone both [18F]FES PET/CT and [18F]FDG PET/CT. Two readers assessed both images independently and used a patient-based (PBA) and lesion-based analysis (LBA) to calculate the DR. Pathology-related and clinical factors were tested as predictors of [18F]FES PET/CT superiority using a multivariate model. RESULTS: 92 patients, bearing a total of 2678 metastases, were enrolled. On PBA, the DR of [18F]FDG and [18F]FES PET/CT was 97% and 86%, respectively (p = 0.018). On LBA, the [18F]FES method proved more sensitive than [18F]FDG PET/CT in lymph nodes, bone, lung and soft tissue (p < 0.01). This greater sensitivity was associated with lobular histology, both on PBA (Odds Ratio (OR) 3.4, 95%CI 1.0-12.3) and on LBA (OR 4.4, 95%CI 1.2-16.1 for lymph node metastases and OR 3.29, 95%CI 1.1-10.2 for bone localizations). CONCLUSIONS: The overall DR of [18F]FES PET/CT appears to be lower than that of [18F]FDG PET/CT on PBA. However, the [18F]FES method, if positive, can identify more lesions than [18F]FDG at most sites. The higher sensitivity of [18F]FES PET/CT was associated with lobular histology.

131 I-Meta-iodobenzylguanidine followed by busulfan and melphalan and autologous stem cell rescue in high-risk neuroblastoma.

INTRODUCTION: Despite the progress in current treatments, the event-free survival of high-risk neuroblastoma (HR-NB) patients does not exceed 40%-50%, and the prognosis of refractory or relapsed patients is poor, still representing a challenge for pediatric oncologist. Therapeutic Iodine-131 meta-iodobenzylguanidine (Th-131 I-MIBG) is a recognized safe and potentially effective treatment for NB. MATERIALS: This retrospective study reports the outcomes of 28 MIBG-avid NB patients with advanced disease either refractory or relapsed, which was undertaken from 1996 to 2014. Th-131 I-MIBG was administered shortly before (median: 17 days) high-dose chemotherapy with busulfan and melphalan (HD-BuMel) and autologous stem cell rescue (ASCR) at the Gaslini Institute in Genoa, with the aim of analyzing the feasibility, safety, and efficacy of this approach. RESULTS: Engraftment occurred in all patients after a median of 14 (11-29) and 30 days (13-80) from ASCR for neutrophils and platelets, respectively. No treatment-related deaths were observed. The main high-grade (3-4) toxicity observed was oral and gastrointestinal mucositis in 78.6% and 7.1% of patients, respectively, whereas high-grade hepatic toxicity was observed in 10.7%. Two patients developed veno-occlusive-disease (7.1%), completely responsive to defibrotide. Hypothyroidism was the main late complication that occurred in nine patients (31.1%). After Th-131 MIBG and HD-BuMel, 19 patients (67.8%) showed an improvement in disease status. Over a median follow-up of 15.9 years, the three-year and five-year overall survival (OS) probabilities were 53% (CI 0.33-0.69) and 41% (CI 0.22-0.59), and the three-year and five-year rates of cumulative risk of progression/relapse were 64% (CI 0.47-0.81) and 73% (CI 0.55-0.88), respectively. MYCN amplification emerged as the only risk factor significantly associated with OS (HR, 3.58;P = 0.041). CONCLUSION: Th-131 I-MIBG administered shortly before HD-BuMel is a safe and effective regimen for patients with advanced MIBG-avid NB. These patients should be managed in centers with proven expertise.

Systemic antibiotics in hidradenitis suppurativa: efficacy and effects of body mass index and smoking pack-year on the response to therapy.

The combination of oral clindamycin with rifampicin is recommended by European guidelines as a first-line treatment in moderate-to-severe hidradenitis suppurativa (HS). Recent studies highlight that oral clindamycin in monotherapy (CM) may be a useful alternative treatment. We included 36 patients with a diagnosis of moderate-to-severe HS. A total of 19 patients were treated with combination oral clindamycin plus rifampicin (C + R) and 17 with oral CM for 12 weeks. The efficacy of CM vs C + R was analyzed by multilinear regression models which showed a higher reduction in mSartorius (Δ = -13.2, P = .058) and AISI (Δ = -4.91, P = .034) in the C + R group. In the C + R group, smoking pack-year was positively correlated with AISI (Spearman's rho = 0.51, P = .036) and with DLQI (0.47, P = .061). In the CM group, a positive correlation was found between BMI and AISI (0.47, P = .041). The data on the efficacy of C + R combination therapy are in line with guidelines, evidence-based approaches, and recommendations from the HS ALLIANCE working group. The rationale for combining these two drugs is to increase bactericidal action and to reduce rifampicin resistance, as rifampicin is highly mutagenic. Our results suggest that the antibiotic combination of C + R is still the treatment of choice in moderate-to-severe HS with abscesses, draining fistulae and ≥ 5 inflammatory nodules. High BMI and smoking habits seem to be predictive factors of a poor response to antibiotics. Further multicenter studies and prospective randomized controlled trials are needed to confirm these results. Potential alternative antibiotic therapies should also be investigated.

Patient- versus physician-reported outcomes in a low-dose tamoxifen trial in noninvasive breast cancer.

BACKGROUND: We recently conducted a de-escalation trial of low-dose tamoxifen 5 mg/day ("babytam", BT) or placebo given for 3 years in 500 women with noninvasive breast cancer. Women on babytam had a 52% reduction of recurrence (invasive breast cancer or DCIS) after 5 years. Since menopausal symptoms are major reasons for treatment withdrawal during tamoxifen preventive therapy, we compared and analyzed the patient-reported outcomes (PROs) with the physician-reported adverse events and studied their association with recurrence. METHODS: Menopausal symptoms recorded by physicians using the Common Terminology Criteria (CTCAEs) were compared with a patient self-reported validated questionnaire reviewed by a research nurse at baseline and every 6 months up to 36 months. Hot flashes (HF), the main outcome measure, were detected through a self-report 7-day diary for frequency and intensity. Treatment adherence and efficacy were assessed by the Kaplan-Meier curves and the Cox model. RESULTS: The number of HF events at 12, 24, and 36 months for PROs versus CTCAEs was 246 versus 12, 238 versus 8, and 210 versus 4, respectively. The majority of events were grade 1. There was no difference in PROs between babytam and placebo except for HF daily frequency, which increased by 1.5 events (95% CI, 1.1-1.8) on placebo to 2.1 on babytam (95% CI, 1.7-2.5, p = 0.05). The presence of HF at baseline was a favorable prognostic factor for recurrence and a predictive factor for response to babytam. Adherence was similar between babytam and placebo. CONCLUSIONS: The use of PROs is effective for identifying frequent mild grade menopausal symptoms which are underestimated by physicians but important prognostic and predictive factors. Research nurse can use these results as a tool to reassure patients about symptoms, improve adherence to treatment, and limit dropouts.

A Presurgical Study of Curcumin Combined with Anthocyanin Supplements in Patients with Colorectal Adenomatous Polyps.

Adenomatous polyps are precancerous lesions associated with a higher risk of colorectal cancer (CRC). Curcumin and anthocyanins have shown promising CRC-preventive activity in preclinical and epidemiological studies. The objective of this window-of-opportunity, proof-of principle trial was to evaluate the effect of curcumin combined with anthocyanin supplements on tissue biomarkers of colorectal adenomatous polyps. Eligible patients received either anthocyanin and curcumin supplementation or related matching placebo for 4-6 weeks before polyp removal. Adenomatous polyps and adjacent tissue biopsies were collected at baseline and after supplementation for immunohistochemical assessment of ß-catenin, NF-kappa B (NF-κB), Ki-67, P53, and dysplasia. No differences were observed in baseline biomarker expression between normal and dysplastic tissues. The combination of anthocyanins and curcumin resulted in a significant borderline reduction of NF-κB immunohistochemistry (IHC) expression in adenoma tissue (geometric mean ratio (GMR): 0.72; 95% confidence interval (CI): 0.51-1.00; p-value: 0.05) and a trend to a reduction of Ki-67 (GMR: 0.73; 95% CI: 0.50-1.08; p-value: 0.11). No significant modulation of biomarkers in normal adjacent mucosa was observed. We concluded that the combined supplementation of anthocyanins and curcumin seems to lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas.

Robotic balance assessment in community-dwelling older people with different grades of impairment of physical performance.

BACKGROUND: Impaired physical performance is common in older adults and has been identified as a major risk factor for falls. To date, there are no conclusive data on the impairment of balance parameters in older subjects with different levels of physical performance. AIMS: The aim of this study was to investigate the relationship between different grades of physical performance, as assessed by the Short Physical Performance Battery (SPPB), and the multidimensional balance control parameters, as measured by means of a robotic system, in community-dwelling older adults. METHODS: This study enrolled subjects aged ≥ 65 years. Balance parameters were assessed by the hunova robot in static and dynamic (unstable and perturbating) conditions, in both standing and seated positions and with the eyes open/closed. RESULTS: The study population consisted of 96 subjects (62 females, mean age 77.2 ± 6.5 years). According to their SPPB scores, subjects were separated into poor performers (SPPB < 8, n = 29), intermediate performers (SPPB = 8-9, n = 29) and good performers (SPPB > 9, n = 38). Poor performers displayed significantly worse balance control, showing impaired trunk control in most of the standing and sitting balance tests, especially in dynamic (both with unstable and perturbating platform/seat) conditions. CONCLUSIONS: For the first time, multidimensional balance parameters, as detected by the hunova robotic system, were significantly correlated with SPPB functional performances in community-dwelling older subjects. In addition, balance parameters in dynamic conditions proved to be more sensitive in detecting balance impairments than static tests.

Pathogenesis of Leprosy: An Insight Into B Lymphocytes and Plasma Cells.

The pathogenesis of leprosy is still not fully understood. Several studies have been performed on the involvement of T cells in leprosy and more recently have focused on genetic factors and innate immune response. There are still only few reports about the role of B cells in active leprosy lesions in different spectral forms of the disease. The literature on tuberculosis suggests that B cells play an important role in the regulation of the granulomas, in cytokine production, T-cell response, and antigen presentation. Only few studies investigated the role of B cell in leprosy. We investigated the distribution of B cells in 85 leprosy biopsies covering all forms of the disease and compared results with 13 biopsies of tuberculosis and atypical mycobacteriosis, expanding the previous experiences. A statistically significant difference in the number of CD20 (P = 0.014) and CD138+ (P = 0.01) cells between the different forms of leprosy was observed. A remarkable amount of CD138+ cells could also be detected in borderline tuberculoid. The median of the CD20 cells decreased from the bacilloscopy-negative samples to the bacilloscopy-positive samples by 50% (P = 0.004). Contrarily, the median of CD138+ cells showed an increase from bacilloscopy-negative to bacilloscopy-positive samples of 966.67% (P = 0.001). In our experience, tuberculoid leprosy showed more B cells and less plasma cells than lepromatous leprosy. Our results show that B cells might be implicated in leprosy pathogenesis, not only in the lepromatous pole as previously postulated, but also in tuberculoid granuloma formation and type 1 reactions.

Prognostic value of chromosomal imbalances, gene mutations, and BAP1 expression in uveal melanoma.

Uveal melanoma (UM) exhibits recurring chromosomal abnormalities and gene driver mutations, which are related to tumor evolution/progression. Almost half of the patients with UM develop distant metastases, predominantly to the liver, and so far there are no effective adjuvant therapies. An accurate UM genetic profile could assess the individual patient's metastatic risk, and provide the basis to determine an individualized targeted therapeutic strategy for each UM patient. To investigate the presence of specific chromosomal and gene alterations, BAP1 protein expression, and their relationship with distant progression free survival (DPFS), we analyzed tumor samples from 63 UM patients (40 men and 23 women, with a median age of 64 years), who underwent eye enucleation by a single cancer ophthalmologist from December 2005 to June 2016. UM samples were screened for the presence of losses/gains in chromosomes 1p, 3, 6p, and 8q, and for mutations in GNAQ, GNA11, BAP1, SF3B1, and EIF1AX. BAP1 protein expression was detected by immunohistochemistry (IHC). Multivariate analysis showed that the presence of monosomy 3, 8q gain, and loss of BAP1 protein were significantly associated to DPFS, while BAP1 gene mutation was not, mainly due to the presence of metastatic UM cases with negative BAP1 IHC and no BAP1 mutation detected by Sanger sequencing. Loss of BAP1 protein expression and monosomy 3 represent the strongest predictors of metastases, and may have important implications for implementation of patient surveillance, properly designed clinical trials enrollment, and adjuvant therapy.

Could short thyroid hormone withdrawal be an effective strategy for radioiodine remnant ablation in differentiated thyroid cancer patients?

PURPOSE: Current guidelines recommend thyroid hormone withdrawal (THW) of 3-4 weeks before radioiodine remnant ablation (RRA) of differentiated thyroid carcinoma (DTC). We aimed to evaluate (1) the reliability of a shorter THW (i.e., 14 days) to achieve adequate TSH levels (i.e., 30 mU/l), (2) the association between length of THW and response to therapy, and (3) the potential association between pre-ablation TSH levels and patients' outcome. METHODS: After thyroidectomy, all patients started LT4 therapy, which was subsequently discontinued in order to perform RRA. Patients were broken down into two groups according to the length of THW: group A, 2 weeks of THW, and group B, 3-4 weeks of THW. We used clinical, biochemical, and imaging data to evaluate patients' outcome. By means of univariate and multivariate analysis, including main DTC prognostic factors, we assessed the impact of THW length and TSH levels on patients' outcome. RESULTS: We evaluated 222 patients, 85 of whom were treated with RRA after a THW period of 2 weeks (group A). All other 137 patients underwent RRA after 3-4 weeks THW (group B). At the time of RRA all patients presented TSH levels ≥30 mU/l. After a median follow-up time of 3.4 years, we found 183 patients (82%) with excellent response to treatment and 39 patients (18%) showing incomplete response. Kaplan-Meier response to therapy curves showed that ablation-Tg, tumor size, and lymph node status were significantly associated with prognosis; no associations were found between THW length, TSH levels, and prognosis. Multivariate Cox model showed that only ablation-Tg was significantly associated with treatment response. CONCLUSIONS: Prior to RRA, a short 2-week THW is an effective method to stimulate TSH levels. No difference in terms of incomplete response to treatment was observed between DTC patients prepared for RRA with a short THW and those with the long THW.

The ASAMET trial: a randomized, phase II, double-blind, placebo-controlled, multicenter, 2 × 2 factorial biomarker study of tertiary prevention with low-dose aspirin and metformin in stage I-III colorectal cancer patients.

BACKGROUND: Epidemiological studies and cardiovascular prevention trials have shown that low-dose aspirin can reduce colorectal cancer (CRC) incidence and mortality, including inhibition of distant metastases. Metformin has also been associated with decreased colon adenoma recurrence in clinical trials and lower CRC incidence and mortality in epidemiological studies in diabetics. While both drugs have been tested as single agents, their combination has not been tested in cancer prevention trials. METHODS/DESIGN: This is a randomized, placebo-controlled, double-blind, 2 × 2 biomarker trial of aspirin and metformin to test the activity of either agent alone and the potential synergism of their combination on a set of surrogate biomarkers of colorectal carcinogenesis. After surgery, 160 patients with stage I-III CRC are randomly assigned in a four-arm trial to either aspirin (100 mg day), metformin (850 mg bis in die), their combination, or placebo for one year. The primary endpoint biomarker is the change of IHC expression of nuclear factor kappa-B (NFκB) in the unaffected mucosa of proximal and distal colon obtained by multiple biopsies in two paired colonoscopies one year apart. Additional biomarkers will include: 1) the measurement of circulating IL-6, CRP and VEGF; 2) the IHC expression of tissue pS6K, p53, beta-catenin, PI3K; 3) the associations of genetic markers with treatment response as assessed by next generation sequencing of primary tumors; 4) the genomic profile of candidate genes, pathways, and overall genomic patterns in tissue biopsies by genome wide gene expression arrays; and 5) the evaluation of adenoma occurrence at 1 year. DISCUSSION: A favorable biomarker modulation by aspirin and metformin may provide important clues for a subsequent phase III adjuvant trial aimed at preventing second primary cancer, delaying recurrence and improving prognosis in patients with CRC. TRIAL REGISTRATION: EudraCT Number: 2015-004824-77; ClinicalTrial.gov Identifier: NCT03047837 . Registered on February 1, 2017.

Grading and outcome prediction of pediatric diffuse astrocytic tumors with diffusion and arterial spin labeling perfusion MRI in comparison with 18F-DOPA PET.

PURPOSE: The aim of this study was to investigate MRI-derived diffusion weighted imaging (DWI) and arterial spin labeling (ASL) perfusion imaging in comparison with 18F-dihydroxyphenylalanine (DOPA) PET with respect to diagnostic performance in tumor grading and outcome prediction in pediatric patients with diffuse astrocytic tumors (DAT). METHODS: We retrospectively analyzed 26 children with histologically proven treatment naïve low and high grade DAT who underwent ASL and DWI performed within 2 weeks of 18F-DOPA PET. Relative ASL-derived cerebral blood flow max (rCBF max) and DWI-derived minimum apparent diffusion coefficient (rADC min) were compared with 18F-DOPA uptake tumor/normal tissue (T/N) and tumor/striatum (T/S) ratios, and correlated with World Health Organization (WHO) tumor grade and progression-free survival (PFS). Statistics included Pearson's chi-square and Mann-Whitney U tests, Spearman's rank correlation, receiver operating characteristic (ROC) analysis, discriminant function analysis (DFA), Kaplan-Meier survival curve, and Cox analysis. RESULTS: A significant correlation was demonstrated between rCBF max, rADC min, and 18F-DOPA PET data (p < 0.001). Significant differences in terms of rCBF max, rADC min, and 18F-DOPA uptake were found between low- and high-grade DAT (p ≤ 0.001). ROC analysis and DFA demonstrated that T/S and T/N values were the best parameters for predicting tumor progression (AUC 0.93, p < 0.001). On univariate analysis, all diagnostic tools correlated with PFS (p ≤ 0.001); however, on multivariate analysis, only 18F-DOPA uptake remained significantly associated with outcome (p ≤ 0.03), while a trend emerged for rCBF max (p = 0.09) and rADC min (p = 0.08). The combination of MRI and PET data increased the predictive power for prognosticating tumor progression (AUC 0.97, p < 0.001). CONCLUSIONS: DWI, ASL and 18F-DOPA PET provide useful complementary information for pediatric DAT grading. 18F-DOPA uptake better correlates with PFS prediction. Combining MRI and PET data provides the highest predictive power for prognosticating tumor progression suggesting a synergistic role of these diagnostic tools.

Differentiated Thyroid Cancer lymph-node relapse. Role of adjuvant radioactive iodine therapy after lymphadenectomy.

PURPOSE: Our purpose as to evaluate the impact of adjuvant radioactive iodine therapy (RAI) on prognosis, as assessed by progression-free survival (PFS) and overall survival (OS), in patients affected by differentiated thyroid carcinoma (DTC) lymph-node relapse and previously treated with lymphadenectomy. METHODS: We retrospectively evaluated DTC patients treated with lymph-node dissection for disease relapse. All patients had previously undergone total thyroidectomy and radioiodine remnant ablation (RRA). We used clinical and histological data obtained during follow-up to assess response and outcome. By means of univariate and multivariate time-to-event analyses, we assessed the impact of RAI on outcome (PFS and OS) and the prognostic role of thyroglobulin (Tg) levels under suppression with levothyroxine (Tg-on) measured 1-3 months after lymphadenectomy and of other risk factors. RESULTS: We evaluated 113 patients (age at diagnosis: median 41 years, interquartile range: 31-59), 64 of whom were treated with RAI. Over a median follow-up time of 5.7 years, 27 patients showed disease progression and 13 died. Kaplan-Meier PFS and OS curves showed that age on diagnosis, tumor histology, tumor size, DTC aggressive variant, and Tg-on were associated with prognosis. Patients with Tg-on ≥1 ng/ml treated with RAI showed a better PFS (Log-rank pp 0.001) and OS (p = 0.005) than untreated patients, while no effect of RAI was observed in patients with Tg-on <1 ng/ml. Multivariate models showed that age, Tg-on (≥1 vs. < 1 ng/ml, HR: 18.2, 95% CI: 5.09-64.8, p = 0.001) and RAI (Yes vs. No, HR: 0.36,95%CI: 0.15-0. 9, p = 0.02) remained the only independent factors associated with PFS, but only age and Tg-on remained significantly associated with OS (HR: 8.31, 95%CI:1.56-44.3, p = 0.01). Nonetheless, patients treated with RAI showed a lower risk of mortality (HR: 0.34, 95%CI: 0.1-1.15 p = 0.08) than untreated patients. CONCLUSIONS: RAI after lymphadenectomy for DTC relapse is significantly associated with better PFS only in patients with Tg-on ≥1 ng/ml.

Clinical benefit and risk of death with endocrine therapy in ovarian cancer: A comprehensive review and meta-analysis.

BACKGROUND: Steroid hormones promote epithelial ovarian cancer (EOC) growth and their receptor expression is associated with disease outcome. Hormone therapy is frequently used in pretreated EOC, but the magnitude of activity overall and by specific agents or tumor characteristics is unknown. METHODS: Clinical Benefit Rates (CBR) and deaths from clinical trials of endocrine agents were meta-analyzed. Summary estimates of CBR (SCBR) and Odd Ratio for death (SOR) were calculated according with type of drug, ER and PgR status, platinum resistance, line of therapy, tumor grade and tamoxifen dose. RESULTS: Fifty-three trials in 2490 patients were analyzed. Overall, SCBR was 41% (95%CI, 0.34-0.48) for any endocrine treatment, 43% (95%CI, 0.30-0.56) for tamoxifen, 39% (95%CI, 0.29-0.50) for aromatase inhibitors and 37% (95%CI, 0.26-0.48) for progestins. The SCBR for ER+ and/or PgR+ tumors was 46% (95%CI, 0.34-0.57) versus 37% (95%CI, 0.27-0.48) in tumors with unknown receptors and 55% in platinum sensitive (95%CI, 0.28-0.80) versus 40% (95%CI, 0.29-0.51) in platinum resistant tumors The SOR for death calculated from 6 out of 9 randomized clinical trials (RCTs) showed a reduced mortality with endocrine therapy (SOR=0.69, 95%CI, 0.50-0.97), with a possible tendency for a greater effect in first line and low grade tumors. The overall quality of the RCTs was low. CONCLUSIONS: The activity of endocrine therapy in advanced EOC is worth considering and seems to support large properly designed randomized trials in the first treatment of hormone sensitive EOC.

Is CT perfusion helpful in the treatment allocation of patients with acute ischemic stroke? An expert-opinion analysis.

BACKGROUND: Intravenous tPA is the standard treatment for acute ischemic stroke within 4.5 hours of symptom onset. Neuroradiological selection is currently based upon non-contrast- brain CT scan (NCCT). AIMS: To verify, in an "expert-opinion setting", the possible usefulness of CT perfusion (CTP) in decision-making toward i.v. thrombolysis. PATIENTS AND METHOD: One hundred and three consecutive patients with acute ischemic stroke who underwent NCCT and CTP were re-evaluated by an expert in cerebrovascular disease, to verify if adding CTP information would have changed expert's opinion. RESULTS: After CTP, a definitive decision was made for 20 more patients, changing the proportion of patients candidate to i.v. tPA from 44% to 51%, and reducing uncertainty from 29% to 10%. CTP results were useful inmilder stroke (p = 0.01). CONCLUSIONS: In a "real world" setting, CT perfusion could be useful for clinical decision, in particular for milder stroke.

Frailty is associated with socioeconomic and lifestyle factors in community-dwelling older subjects.

BACKGROUND AND AIMS: This study assessed the association between frailty and sociodemographic, socioeconomic and lifestyle factors in community-dwelling older people. METHODS: This was a cross-sectional survey in a population-based sample of 542 community-dwelling subjects aged 65 years and older living in a metropolitan area in Italy. Frailty was evaluated by means of the FRAIL scale proposed by the International Association of Nutrition and Aging. Basal and instrumental activities of daily living (ADL, IADL), physical activity, sociodemographic (age, gender, marital status and cohabitation), socioeconomic (education, economic conditions and occupational status) and lifestyle domains (cultural and technological fruition and social activation) were assessed through specific validated tools. Statistical analysis was performed through multinomial logistic regression. RESULTS: Impairments in ADL and IADL were significantly associated with frailty, while moderate and high physical activity were inversely associated with frailty. Moreover, regarding both socioeconomic variables and lifestyle factors, more disadvantaged socioeconomic conditions and low levels of cultural fruition were significantly associated with frailty. CONCLUSIONS: Socioeconomic and lifestyle factors, particularly cultural fruition, are associated with frailty independently from functional impairment and low physical activity. Cultural habits may therefore represent a new target of multimodal interventions against geriatric frailty.

Ability of (18)F-DOPA PET/CT and fused (18)F-DOPA PET/MRI to assess striatal involvement in paediatric glioma.

PURPOSE: To assess the diagnostic performance of (18)F-DOPA PET/CT and fused (18)F-DOPA PET/MRI in detecting striatal involvement in children with gliomas. METHODS: This retrospective study included 28 paediatric patients referred to our institution for the presence of primary, residual or recurrent glioma (12 boys, 16 girls; mean age 10.7 years) and investigated with (18)F-DOPA PET/CT and brain MRI. Fused (18)F-DOPA PET/MR images were obtained and compared with PET/CT and MRI images. Accuracy, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for striatal involvement were calculated for each diagnostic tool. Univariate and multivariate logistic analyses were applied to evaluate the associations between (18)F-DOPA PET/CT and fused (18)F-DOPA PET/MRI diagnostic results and tumour uptake outside the striatum, grade, dimension and site of striatal involvement (ventral and/or dorsal). RESULTS: Accuracy, sensitivity, specificity, PPV, and NPV were 100 % for MRI, 93 %, 89 %, 100 %, 100 % and 82 % for (18)F-DOPA PET/MRI, and 75 %, 74 %, 78 %, 88 % and 58 % for (18)F-DOPA PET/CT, respectively. (18)F-DOPA PET/MRI showed a trend towards higher accuracy compared with (18)F-DOPA PET/CT (p = 0.06). MRI showed significantly higher accuracy compared with (18)F-DOPA PET/CT (p = 0.01), but there was no significant difference between MRI and (18)F-DOPA PET/MRI. Both univariate and multivariate logistic analyses showed a significant association (OR 8.0 and 7.7, respectively) between the tumour-to-normal striatal uptake (T/S) ratio and the diagnostic ability of (18)F-DOPA PET/CT (p = 0.03). A strong significant association was also found between involvement of the dorsal striatum and the (18)F-DOPA PET/CT results (p = 0.001), with a perfect prediction of involvement of the dorsal striatum by (18)F-DOPA PET/MRI. CONCLUSION: Physiological striatal (18)F-DOPA uptake does not appear to be a main limitation in the evaluation of basal ganglia involvement.(18)F-DOPA PET/CT correctly detected involvement of the dorsal striatum in lesions with a T/S ratio >1, but appeared to be less suitable for evaluation of the ventral striatum. The use of fused (18)F-DOPA PET/MRI further improves the accuracy and is essential for evaluation of the ventral striatum.

Breast cancer incidence after hormonal treatments for infertility: systematic review and meta-analysis of population-based studies.

The increasing practice of hormonal infertility treatments (HITs) raised concerns about their effects on breast cancer (BC) risk. Available evidence reported conflicting results. The aim of this study was to assess the potential association between HITs and BC risk. The literature was searched through November 2014. Eligible studies included cohort studies reporting BC incidence in women undergone HITs. Data were analyzed with standard meta-analytic techniques. Subgroup analyses were performed by type of intervention (IVF vs. NO IVF), follow-up duration (<10 vs. >10 years), and type of control (population vs. infertile). 20 eligible studies (207.914 women, 2347 BC) were retrieved: no increased risk was detected (SRR = 1.05, 95 % CI 0.96-1.14), with a significant heterogeneity (I (2) = 59 %, p = 0.001) among studies. In the seven studies with the in vitro fertilization (IVF) procedure, no increase in BC risk was observed (SRR = 0.96, 95 % CI 0.80-1.14); in the three NO IVF studies, an increased BC risk was identified (SRR = 1.26, 95 %CI 1.06-1.50). A borderline interaction between type of intervention (IVF vs. NO IVF) and BC risk was observed (p = 0.06). An increased risk with longer follow-up (≥10 vs. <10 years) was detected (SRR = 1.13, 95 % CI 1.02-1.26 vs. SRR = 0.95, 95 % CI 0.85-1.06). Overall, HITs are not associated with an increased BC risk. In particular, no increased risk was observed in women undergoing IVF. Conversely, an increased in BC risk cannot be ruled out with older treatment protocols based on clomiphene. The long-term administration of clomiphene outside the current indications should be discouraged because of a possible increase in BC risk.

Determination of deferasirox plasma concentrations: do gender, physical and genetic differences affect chelation efficacy?

OBJECTIVES: Bioavailability of deferasirox (DFX) is significantly affected by the timing of administration relative to times and to composition of meals. Its elimination half-life is also highly variable - in some patients as a result of gene polymorphisms. Understanding whether deferasirox plasma levels are related to specific characteristics of patients could help physicians to devise a drug regimen tailored the individual patient. METHODS: We analyzed deferasirox plasma concentrations (CDFX ) in 80 patients with transfusion-dependent anemias, such as thalassemia, by a high performance liquid chromatography (HPLC) assay. We used a multivariate linear regression model to find significant associations between CDFX and clinical/demographical characteristics of patients. All patients were genotyped for UGT1A1. RESULTS: Fifty-six patients were female, 24 were male, the great majority (88%) affected by ß-thalassemia, and 15 were children and adolescents. No statistical correlation was detectable between CDFX and DFX dose (P = 0.6). Age, time from last drug intake to blood sampling, and ferritin levels in the 6 months before study initiation were significantly and inversely associated with CDFX in univariate analysis. In the multivariate analysis, the only two factors independently and inversely associated with CDFX levels were time from last drug intake to blood sampling and ferritin levels (P = 0.006). A significant inverse correlation (P = 0.03) was observed between CDFX and UGT1A1*28 gene polymorphism, but only in patients with levels of lean body mass (LBM) below the median (P for interaction = 0.05). CONCLUSIONS: The results could indicate that a higher plasma DFX concentration could be associated with greater chelation efficacy. As a correlation between dose and CDFX was not demonstrated, it seems useful to monitor the concentrations to optimize and determine the most appropriate dose for each patient. Interesting results emerged from the analysis of genetic and physical characteristics of patients: LBM was a borderline significant effect modifier of the relationship between UGT1A1 polymorphisms and CDFX . Individual patient-tailored dosing of DFX should help to improve iron chelation efficacy and to reduce dose-dependent drug toxicity.