Search

Objectives: The primary objective of this study was the translation and validation of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire into Italian, denoted as AAV-PRO&#95;ita. The secondary objective was to evaluate the impact of ANCA-associated vasculitis (AAV) on quality of life (QoL) and work impairment in a large cohort of Italian patients., Methods: The study design took a prospective cohort study approach. First, the AAV-PRO was translated into Italian following the step guidelines for translations. The new AAV-PRO&#95;ita questionnaire covered three disease domains: organ-specific and systemic symptoms and signs; physical function; and social and emotional impact. Second, Italian-speaking AAV patients were recruited from 17 Italian centres belonging to the Italian Vasculitis Study Group. Participants completed the AAV-PRO&#95;ita questionnaire at three time points. Participants were also requested to complete the work productivity and activity impairment: general health questionnaire., Results: A total of 276 AAV patients (56.5% women) completed the questionnaires. The AAV-PRO&#95;ita questionnaire demonstrated a good internal consistency and test-retest reliability. Female AAV patients scored higher (i.e. worse) in all thee domains, especially in the social and emotional impact domain ( P  < 0.001). Patients on glucocorticoid therapy ( n  = 199) had higher scores in all domains, especially in the physical function domain ( P  < 0.001), compared with patients not on glucocorticoid therapy ( n  = 77). Furthermore, patients who had at least one relapse of disease ( n  = 114) had higher scores compared with those who had never had one ( n  = 161) in any domain ( P  < 0.05). Finally, nearly 30% of the patients reported work impairment., Conclusion: The AAV-PRO&#95;ita questionnaire is a new 29-item, disease-specific patient-reported outcome measuring tool that can be used in AAV research in the Italian language. Sex, glucocorticoids and relapsing disease showed the greatest impact on QoL., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Liposuction is a safe, simple, and effective method of body contouring. Pain, ecchymosis, and edema are often local complications at the removal site, especially in the first weeks after surgery. Several studies have shown that kinesiology (kinesio) taping improves blood and lymphatic flow, removing congestions of lymphatic fluid and alleviating hemorrhage. However, there are limited data on the effect of kinesio taping in mitigating local complications at fat grafting donor sites., Objectives: The aim of this pilot study was to evaluate the impact of kinesio taping in reducing postoperative edema, pain, and ecchymosis in the liposuction area., Methods: Over a period of 18 months (January 2021-June 2022), 52 patients underwent liposuction of both flanks with subsequent breast fat grafting. Immediately after the surgery, kinesio taping was used on the right abdomen flank in all patients. Degree of edema as well as ecchymosis and pain were quantified at 7, 14, and 21 days after surgery., Results: There were statistically significant differences in the taping area for ecchymosis at 7 days after surgery, edema at 14 and 21 days after surgery, and in pain, rated on a visual analog scale, at 7, 14 and 21 days after surgery., Conclusions: Kinesio taping, as used in this study, is beneficial in the reduction of edema and pain and the resolution of ecchymosis after liposuction., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Parotid swelling (PSW) is a major predictor of non-Hodgkin's lymphoma (NHL) in primary SS (pSS). However, since detailed information on the time of onset and duration of PSW is scarce, this was investigated to verify whether it may lead to further improved prediction. NHL localization was concomitantly studied to evaluate the role of the parotid gland microenvironment in pSS-related lymphomagenesis., Methods: A multicentre study was conducted among patients with pSS who developed B cell NHL during follow-up and matched controls that did not develop NHL. The study focused on the history of salivary gland and lachrymal gland swelling, evaluated in detail at different times and for different durations, and on the localization of NHL at onset., Results: PSW was significantly more frequent among the cases: at the time of first referred pSS symptoms before diagnosis, at diagnosis and from pSS diagnosis to NHL. The duration of PSW was evaluated starting from pSS diagnosis, and the NHL risk increased from PSW of 2-12 months to >12 months. NHL was prevalently localized in the parotid glands of the cases., Conclusion: A more precise clinical recording of PSW can improve lymphoma prediction in pSS. PSW as a very early symptom is a predictor, and a longer duration of PSW is associated with a higher risk of NHL. Since lymphoma usually localizes in the parotid glands, and not in the other salivary or lachrymal glands, the parotid microenvironment appears to be involved in the whole history of pSS and related lymphomagenesis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: While recent genome-wide association studies have suggested novel low-grade glioma (LGG) stratification models based on a molecular classification, we explored the potential clinical utility of patient-derived cells. Specifically, we assayed glioma-associated stem cells (GASC) that are patient-derived and representative of the glioma microenvironment., Methods: By next-generation sequencing, we analyzed the transcriptional profile of GASC derived from patients who underwent anaplastic transformation either within 48 months (GASC-BAD) or ≥7 years (GASC-GOOD) after surgery. Gene set enrichment and pathway enrichment analyses were applied. The prognostic role of a nuclear factor-kappaB (NF-κB) signature derived from GASC-BAD was tested in 530 newly diagnosed diffuse LGG patients comprised within The Cancer Genome Atlas (TCGA) database. The prognostic value of the GASC upstream regulator p65 NF-κB was assessed, by univariate and multivariate Cox analyses, in a single center case study, including 146 grade II LGGs., Results: The key elements differentiating the transcriptome of GASC isolated from LGG with different prognoses were mostly related to hallmarks of cancer (eg, inflammatory/immune process, NF-κB activation). Consistently, the NF-κB signature extrapolated from the GASC study was prognostic in the dataset of TCGA. Finally, the nuclear expression of the NF-kB-p65 protein, assessed using an inexpensive immunohistochemical method, was an independent predictor of both overall survival and malignant progression-free survival in 146 grade II LGGs., Conclusion: This study demonstrates for the first time the independent prognostic role of NF-kB activation in LGG and outlines the role of patient-based stem cell models as a tool for precision medicine approaches.

Objectives: Surgical aortic valve replacement (SAVR) for the treatment of in very old patients with severe aortic stenosis is associated with a high risk of morbidity and mortality. Transcatheter aortic valve implantation (TAVI) has become the preferred alternative. Therefore, we sought to evaluate outcomes in very old patients who underwent SAVR versus TAVI., Methods: A total of 169 consecutive patients aged ≥85 years underwent TAVI (n = 68) or SAVR (n = 101). A propensity score adjustment was used to compare outcomes including cost analysis., Results: The propensity score generated 40 pairs of patients with similar baseline characteristics. The TAVI group experienced atrioventricular block (37.5% vs 5%, P < 0.01) more frequently, a longer stay in the intensive care unit (median 5 days, range 1-35 vs median 2 days, range 1-6, P < 0.01) but a lower rate of new-onset atrial fibrillation (15% vs 47.5%, P < 0.01). The 30-day mortality rate was similar in the unmatched and matched cohorts (8.8% vs 5.0%, P = 0.32; 10% vs 7.5%, P = 0.69). One, 3- and 5-year overall survival rates (80% vs 90%, 56% vs 79%, 37% vs 71%, P < 0.01) and freedom from major adverse cardiac and cardiovascular events (72% vs 90%, 46% vs 76%, 17% vs 68%, P < 0.01) were lower in the TAVI group. An overall cost analysis indicated that TAVI was more expensive (€2084 vs €19 891)., Conclusions: In patients 85 years and older, SAVR seems to offer good short- and mid-term clinical outcomes compared to TAVI. Advanced age alone would not be an indication for TAVI in old-old patients., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: To investigate the relationship between isoniazid plasma exposure and the likelihood of elevation of ALT (≥51 IU/L) among adult patients with TB., Methods: A retrospective observational study was conducted in patients who underwent periodic monitoring of hepatic function and in whom pharmacokinetic data were collected. Monte Carlo simulation was performed with the intent of identifying the probability of achieving an AUC24 greater than the identified threshold of hepatotoxicity with different dosing regimens (2.5, 5.0 and 7.5 mg/kg/day)., Results: Forty-one out of 185 evaluable patients (22.2%) had an ALT elevation. A mild correlation between isoniazid AUC0-24 and ALT increase was observed (Spearman's ρ = 0.34, P < 0.001). Patients with ALT ≥51 IU/L showed significantly higher isoniazid exposure than those with ALT <51 IU/L (mean AUC24 of 58.33 versus 31.28 mg·h/L, P < 0.001). The probabilities of ALT elevation were 0.82 and 0.12 for isoniazid AUC24 ≥55.0 and <55.0 mg·h/L, respectively. Use of a logistic regression model estimated a likelihood of developing hepatotoxicity of 0.5 and 0.9 when in the presence of an isoniazid AUC24 of 53.7 and 70.0 mg·h/L, respectively. Simulation showed that the standard isoniazid 5 mg/kg daily dose gave a probability of ALT increase of 0.46 for slow acetylators and 0.03 for rapid acetylators., Conclusions: Plasma isoniazid exposure might be a valuable predictor of drug-related hepatotoxicity. Early assessment of isoniazid exposure at the beginning of treatment might allow prompt dosage reduction among those patients who are experiencing drug overexposure, thus containing the risk of hepatotoxicity occurrence., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: To report the efficacy and safety of long-term treatment of SS with belimumab, targeting the B-cell-activating factor., Methods: Patients with primary SS were included in the BELISS open-label phase II study, a 1-year open-label trial, if they were positive for anti-SSA or anti-SSB antibodies and had systemic complications or persistent salivary gland enlargement or early disease or biomarkers of B-cell activation. They received belimumab, 10 mg/kg i.v., at weeks 0, 2 and 4 and then every 4 weeks; if response was observed at week 28, or if the clinician and the patient agreed to continue the study in the absence of side effects, treatment was continued for 1 year. Efficacy and safety were analysed during the 1-year period of treatment., Results: Among the 30 patients recruited, 28 were evaluated at week 28 as already reported. Nineteen terminated the 52-week study, 15 of them being responders and 4 non-responders at week 28. Thirteen of the 15 responders at week 28 also responded at week 52 (86.7%). The improvement in the EULAR Sjögren's Syndrome Disease Activity Index and EULAR Sjögren's Syndrome Patient Reported Index scores observed at week 28 showed a trend to further improvement at week 52, and the amelioration of peculiar EULAR Sjögren's Syndrome Disease Activity Index domains (glandular, lymphadenopathy, articular) appeared of particular relevance. The decrease in biomarkers of B-cell activation observed at week 28 persisted unchanged until week 52, with RF decreasing further. Salivary flow, Schirmer's test and the focus score of salivary biopsy did not change. Safety of treatment was good., Conclusion: Long-term treatment with belimumab may be beneficial in SS. Randomized, double-blind, controlled studies in larger populations are encouraged., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: To report on linezolid exposure in a paediatric population who routinely underwent therapeutic drug monitoring (TDM) for dosage optimization and to assess the factors affecting interpatient variability., Methods: We performed a retrospective study of patients whose plasma C(min) and Cmax levels were measured during linezolid treatment. Adequate exposure was defined as a C(min) of 2-7 mg/L and/or an estimated AUC24 of 160-300 mg · h/L. Patients were divided into two subgroups (Group 1, 2-11 years; Group 2, 12-18 years). Monte Carlo simulation was performed to investigate whether or not the currently recommended dosages might enable a high probability of target attainment (PTA) of two thresholds for linezolid efficacy (AUC24/MIC ≥ 80 or ≥ 100). Data on demographic characteristics, disease, microbiology and haematochemical parameters and outcomes were collected., Results: A total of 23 patients were included. Standard dosages were suboptimal in 50.0% and 44.4% of patients in Group 1 and Group 2, respectively. Among those who underwent multiple instances of TDM, the dosages were increased in 33.3% of cases in both groups, and decreased in 6.6% and 9.5% of cases in Group 1 and Group 2, respectively. Co-treatment with phenobarbital, proton pump inhibitors and amiodarone accounted for most of the variability in C(min) (adjusted R(2) of 0.692). Simulations showed a PTA of ≥ 90% with the current dosing regimens in both groups only for pathogens with an MIC ≤ 1 mg/L., Conclusions: Higher dosages of linezolid may be needed, especially in Group 1 when in the presence of pathogens with an MIC >1 mg/L. The role of TDM should be encouraged for optimization of linezolid exposure in the paediatric setting in the presence of infections caused by pathogens with borderline susceptibility and/or for patients co-treated with drugs that may alter linezolid exposure., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of this study was to validate the classification criteria for cryoglobulinaemic vasculitis (CV)., Methods: Twenty-three centres were involved. New patients with CV (group A) and controls, i.e. subjects with serum cryoglobulins but lacking CV based on the gold standard of clinical judgment (group B) and subjects without cryoglobulins but with clinical features that can be observed in the course of CV (group C), were studied. Positivity of serum cryoglobulins was necessary for CV classification. Sensitivity and specificity of the criteria were calculated by comparing group A vs group B. The group A vs group C comparison was done to demonstrate the possible diagnostic utility of the criteria., Results: The study included 268 patients in group A, 182 controls in group B and 193 controls in group C (small vessel vasculitis, 51.8%). The questionnaire (at least 2/3 positive answers) showed 89.0% sensitivity and 93.4% specificity; the clinical item (at least 3/4 clinical involvement) showed 75.7% sensitivity and 89.0% specificity and the laboratory item (at least 2/3 laboratory data) showed 80.2% sensitivity and 62.4% specificity. The sensitivity and specificity of the classification criteria (at least 2/3 positive items) were 89.9% and 93.5%, respectively. The comparison of group A with group C demonstrated the clinical utility of the criteria in differentiating CV from CV mimickers., Conclusion: Classification criteria for CV were validated in a second, large, international study confirming good sensitivity and specificity in a complex systemic disease., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low-grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state-of-the-art markers, hindering the decision-making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high-grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm., Methods and Findings: We isolated glioma-associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage-independent growth, and supported the malignant properties of both A172 cells and human glioma-stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG-patients. At the multivariate Cox analysis, the GASC-based score was the only independent predictor of overall survival and malignant progression free-survival., Conclusions: The microenvironment of both LGG and HGG hosts non-tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of glioma-initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient-based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma., (© 2013 AlphaMed Press.)

Objective: Primary SS is characterized by an increased risk of lymphoma in patients with prelymphomatous manifestations (i.e. myoepithelial sialadenitis or mixed cryoglobulinaemia). Serum B-lymphocyte stimulator (s-BLyS) levels in SS-related B-cell lymphoproliferative disorders were studied by integrating the results with the disease activity score and with molecular analyses of B-cell expansion in the salivary glands., Methods: Seventy-six primary SS patients (with or without lymphoma or prelymphomatous manifestations), 56 HCV-related cryoglobulinaemic vasculitis patients and 55 controls were studied. s-BLyS and molecular analyses of B-cell expansion in the salivary gland tissues were performed. Patients with SS and persistent parotid swelling underwent parotid biopsy., Results: s-BLyS differed between SS subgroups, higher levels being documented in patients with lymphoma or prelymphomatous manifestations vs SS without [1.85 (0.45-4.12) ng/ml vs 1.12 (0.56-1.98) ng/ml; P < 0.0001]. s-BLyS levels significantly correlated with the European League Against Rheumatism (EULAR) SS disease activity index (r = 0.62, P < 0.0001, Spearman's test). Clonal B-cell expansion in the salivary glands, but not polyclonal B-cell expansion, was associated with higher s-BLyS levels [1.98 (0.45-4.12) ng/ml vs 1.15 (0.56-3.25) ng/ml; P = 0.013)]., Conclusion: Higher s-BLyS levels and tissue clonal B-cell expansion characterize SS with B-cell lymphoproliferative disorders, even at prelymphomatous stages. This subgroup of SS patients showed the highest EULAR SS disease activity index scores. This represents a biologic rationale for targeting both clonal B-cell expansion and s-BLyS overproduction in SS.

Objectives: To investigate the relationship between the pattern of bone marrow (BM) B-cell expansion and the clinical features of mixed cryoglobulinaemia (MC) syndrome., Methods: Fifty-five patients with type II MC syndrome were analysed. Their median age was 64 yrs (range 24-82), the median disease duration was 6 yrs (range 1-26) and the mean follow-up after BM analysis was 2.65 yrs (s.d. = 1.33). Peripheral neuropathy was present in 33 patients (60%), nephritis in 14 (25.4%), skin ulcers in 14 (25.4%) and lymphoma or atypical lymphoproliferative disorder (LPD) in 17/55 (30.9%). Anti-HCV antibodies were found in 43/55 patients (78.2%). BM B-cell expansion was evaluated by a semi-nested PCR amplification of the V-D-J region of the IgH genes., Results: A clonal B-cell expansion in the BM was found in 33/55 (60%) patients, while a polyclonal pattern in 22/55 (40%). A BM pattern of clonal B-cell expansion increased the risk of nephritis of about 10 times [odds ratio (OR) = 10.11, CI95%1.52-67.31], if compared to a polyclonal pattern. In contrast, the risk of skin ulcers was decreased in BM clonal cases (OR = 0.09, CI95%0.02-0.49). Overt lymphomas did not emerge from patients with BM monoclonal expansion (without clinical or histopathological features of lymphoproliferation; or with LPD) in a short-term, consistent with the finding that monoclonality was associated with nephritis and not with an underlying, not recognized lymphoma., Conclusion: BM clonal B-cell expansion is associated with nephritis in MC syndrome. Particular B-cell clones may be preferentially expanded and may play a pathogenic role in MC nephritis.