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Objective. The purpose of this study was to evaluate the long-term survival rate of Methotrexate (MTX) in the peripheral joint involvement of psoriatic arthritis (PsA) in a setting of everyday clinical practice. Methods. This was an observational restrospective study performed using the data from a dermatological-rheumatological PsA clinic. All of the patients evaluated at this clinic from March 1997 to December 2007 who were started on MTX alone, had a three-year follow-up time or had discontinued the therapy were included into the survey. Results. Of the 174 evaluable patients, 104 (59.8%) were still taking MTX after three years of treament. The reasons of therapy discontinuation in the remaining 70 (40.2%) patients were: 34 (19.5%) lost-to-follow-up, 18 (10.3%) adverse events, 14 (8%) inefficacies, and 4 (2.3%) deaths (none related to the therapy). MTX was effective in controlling joint inflammation but not in preventing their deterioration. Overall, adverse events were recorded in 43 patients (36.4% of the 114 patients with a three-year follow-up). No serious side effect occurred in the study population. Conclusions. The results of this study showed that, in a setting of clinical pratice, MTX had a good three-year performance in patients with peripheral PsA. Almost 60% of them were still taking this drug at the end of the study period and the toxicity was more than acceptable. In our opinion, MTX might be considered the non-biological DMARD of choice for the treatment of this condition. However it should be used earlier and at higher doses.

Introduction: There is a lack of quantitative evidence on the role of food innovations-new food ingredients and processing techniques-in the nutrition transition., Objective: Document the distribution of food innovations across 67 high-income (HIC) and middle-income (MIC) countries between 1970 and 2010, and its association with the nutritional composition of food supply., Methods: We used all available data on food patents, as compiled by the European Patent Office, to measure food innovations. We considered innovations directly received by countries from inventors seeking protection in their territories, and those embedded in processed food imports. Food and Agricultural Organization data were used to estimate the associations between international diffusion of food innovations and trends in total food supply and its macronutrient composition, after adjusting for confounding trends in demand-side factors. We identified the role of trade by simulating the changes in average diet due to innovations embedded in food imports., Results: Trends in food innovations were positively and significantly associated with changes in daily per capita calorie supply available for human consumption in MIC between 1990 and 2010 (elasticity of 0.027, 95% CI 0.019 to 0.036). Food innovations were positively correlated with the share of animal and free fats in total food supply (elasticities of 0.044, 95% CI 0.030 to 0.058 for MIC between 1970 and 1989 and 0.023, 95% CI 0.003 to 0.043 for HIC between 1990 and 2010). Food innovations were associated with substitutions from complex carbohydrates towards sugars in total food supply for MIC after 1990 (elasticities of -0.037, 95% CI -0.045 to -0.029 for complex carbs, 0.082, 95% CI 0.066 to 0.098 for sugars). For these countries, the trade channel capturing access to innovations through imports of processed food played a key role., Conclusion: Policy-makers should consider the impacts of the international diffusion of food innovations in assessing the costs and benefits of international trade regulations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that may cause joint destruction and disability. The pharmacological treatment of RA aims at obtaining disease remission by effectively ceasing joint inflammation and arresting progressive bone erosions. Some patients present bone lesions accrual even after controlling joint inflammation with current therapies. Our study aimed to analyze lymphocyte subsets and levels of circulating cytokines in patients with RA with progressive bone erosions., Methods: We enrolled 20 patients with a diagnosis of RA and 12 healthy donors (HD). Patients with RA were divided into patients with bone erosions (RA-BE+) and without bone erosions (RA-BE-). Lymphocyte subsets in peripheral blood were evaluated by flow cytometry. Circulating cytokines levels were evaluated by protein array., Results: The distribution of lymphocyte subsets was not able to separate HD from AR patients and RA-BE+ and RA-BE- in cluster analysis. We observed a significant expansion of CXCR5 - PD1 + T peripheral helper cells (Tph cells) and a reduction in both total memory B cells and switched memory B cells in RA patients compared to HD. We observed an expansion in the frequency of total B cells in RA-BE+ patients compared to RA-BE- patients. Unsupervised hierarchical clustering analysis of 39 cytokines resulted in a fairly good separation of HD from RA patients but not of RA-BE+ patients from RA-BE- patients. RA-BE+ patients showed significantly higher levels of IL-11 and IL-17A than RA-BE- patients., Conclusion: We show that patients with progressive erosive disease are characterized by abnormalities in B cells and in cytokines with a proven role in bone reabsorption. Understanding the role played by B cells and the cytokine IL-11 and IL-17A in progressive erosive disease can help identify novel biomarkers of erosive disease and design treatment approaches aimed at halting joint damage in RA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marasco, Fabbriciani, Rotunno, Longhi, De Luca, de Girolamo and Colombini.)

Declines in marriage and fertility rates in many developed countries have fostered research debate and increasing policy attention. Using longitudinal data from the German Socio-Economic Panel, we analyze the effects of exposure to globalization on fertility and marital behavior in Germany, which was a lowest-low fertility setting until recently. We find that exposure to greater import competition from Eastern Europe led to worse labor market outcomes and lower fertility rates. In contrast, workers in industries that benefited from increased exports had better employment prospects and higher fertility. These effects are driven by low-educated individuals, married men, and full-time workers and reflect changes in the likelihood of having any child (the extensive margin). We find evidence of some fertility postponement and significant effects on completed fertility, but we see little evidence of a significant impact on marital behavior. Our results inform the public debate on fertility rates in settings with lowest-low fertility, such as Germany, during the period under investigation., (Copyright © 2022 The Authors.)

Alzheimer's disease (AD) is associated with modifications in cerebral blood perfusion and autoregulation. Hence, neurovascular coupling (NC) alteration could become a biomarker of the disease. NC might be assessed in clinical settings through multimodal electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). Multimodal EEG-fNIRS was recorded at rest in an ambulatory setting to assess NC and to evaluate the sensitivity and specificity of the methodology to AD. Global NC was evaluated with a general linear model (GLM) framework by regressing whole-head EEG power envelopes in three frequency bands (theta, alpha and beta) with average fNIRS oxy- and deoxy-hemoglobin concentration changes in the frontal and prefrontal cortices. NC was lower in AD compared to healthy controls (HC) with significant differences in the linkage of theta and alpha bands with oxy- and deoxy-hemoglobin, respectively ( p = 0.028 and p = 0.020). Importantly, standalone EEG and fNIRS metrics did not highlight differences between AD and HC. Furthermore, a multivariate data-driven analysis of NC between the three frequency bands and the two hemoglobin species delivered a cross-validated classification performance of AD and HC with an Area Under the Curve, AUC = 0.905 ( p = 2.17 × 10 -5 ). The findings demonstrate that EEG-fNIRS may indeed represent a powerful ecological tool for clinical evaluation of NC and early identification of AD.

Alzheimer's disease (AD) is characterized by working memory (WM) failures that can be assessed at early stages through administering clinical tests. Ecological neuroimaging, such as Electroencephalography (EEG) and functional Near Infrared Spectroscopy (fNIRS), may be employed during these tests to support AD early diagnosis within clinical settings. Multimodal EEG-fNIRS could measure brain activity along with neurovascular coupling (NC) and detect their modifications associated with AD. Data analysis procedures based on signal complexity are suitable to estimate electrical and hemodynamic brain activity or their mutual information (NC) during non-structured experimental paradigms. In this study, sample entropy of whole-head EEG and frontal/prefrontal cortex fNIRS was evaluated to assess brain activity in early AD and healthy controls (HC) during WM tasks (i.e., Rey-Osterrieth complex figure and Raven's progressive matrices). Moreover, conditional entropy between EEG and fNIRS was evaluated as indicative of NC. The findings demonstrated the capability of complexity analysis of multimodal EEG-fNIRS to detect WM decline in AD. Furthermore, a multivariate data-driven analysis, performed on these entropy metrics and based on the General Linear Model, allowed classifying AD and HC with an AUC up to 0.88. EEG-fNIRS may represent a powerful tool for the clinical evaluation of WM decline in early AD.

The long-term performance of prediction scores for venous thromboembolism (VTE) in cancer patients has been poorly investigated. We evaluated the discriminatory performance of the Khorana, PROTECHT, CONKO, and ONKOTEV scores for the first 3-6 months and for 12 months, and re-assessed scores after 3-6 months to determine the influence of variations in patients' risk classification on performance. Retrospective cohort of ambulatory patients with active cancer who were scheduled to receive first or new line of chemotherapy. The primary outcome was symptomatic or incidental VTE. A total of 776 patients were included of whom 540 (70%) had distant metastases. The time-dependent c-statistics of Khorana, PROTECHT, CONKO, and ONKOTEV scores at 6 months were 0.61 (95% CI 0.56 to 0.66), 0.61 (95% CI 0.55 to 0.66), 0.60 (95% CI 0.54 to 0.66), and 0.59 (0.52 to 0.66), respectively, with a tendency to decrease during follow-up. None of the scores discriminated between high and low risk patients at the conventional 3-point positivity threshold. The use of a 2-point positivity threshold improved performance of all scores and captured a higher proportion of VTE. The accuracy of risk scores re-assessed at 3-6 months was modest. The Khorana, PROTECHT, CONKO, and ONKOTEV scores are not sufficiently accurate when used at a conventional threshold of 3 points. Performance improves at positivity threshold of 2 points, as evaluated in recent randomized studies on VTE prophylaxis. Score accuracy tends to decrease over time suggesting the need of periodic re-evaluation to estimate possible variation of risk.

Objective: Alzheimer's disease (AD) is characterized by progressive memory failures and visuospatial impairment. Moreover, AD can be accompanied by autonomic system alterations, which, among other impacts, affect thermoregulatory activity. We here investigate differences in autonomic activity between AD patients and healthy controls (HC), employing a complexity analysis of functional infrared imaging (fIRI) data acquired at rest and during the execution of clinical cognitive and mnemonic tests., Approach: fIRI allows for contactless monitoring of autonomic activity and its thermoregulatory expression without interfering with the psychophysiological state of the subject, preserving free interaction with the doctor. The signal complexity analysis, based on the sample entropy, was compared to a standard frequency-based analysis of autonomic-related signals., Main Results: AD patients exhibited lower complexity of fIRI signals during the tests, which could be indicative of a stronger sympathetic activity with respect to HC. No significant effects were found at rest. No differences were found on employing frequency-based analysis., Significance: This study confirms that AD patients may exhibit peculiar autonomic responses associated with the execution of cognitive tasks that can be measured through fIRI. Moreover, these responses could be highlighted by a nonlinear metric of signal predictability such as the sample entropy establishing autonomic impairment of AD patients.

Objective: To compare the power Doppler ultrasonography (PDUS) pictures of peripheral entheses in patients with psoriatic arthritis (PsA) and fibromyalgia (FM)., Methods: Thirty patients with PsA and 30 with FM participating in a study aimed at identifying the clinical features that distinguish the 2 conditions underwent the PDUS assessment of 14 major peripheral entheses. All of the detected entheseal changes were recorded and scored, and the data were statistically analyzed by means of univariate analysis and receiver-operating characteristic curves., Results: Four hundred twenty entheseal sites were assessed in each group of patients. At least 1 lesion was detected in each of the patients with PsA and in 80% of the patients with FM (p = 0.01), but inflammatory changes were present in respectively 70% and 23% (p = 0.001). A cutoff point of ≥ 3 involved sites had the greatest discriminating power in the patients with PsA, who were the only patients with bony erosions. PDUS signs of plantar fascia enthesopathy and Achilles tendon inflammation were highly specific of PsA., Conclusion: PDUS assessment of the peripheral entheses distinguishes patients with PsA and patients with FM in terms of the number and distribution of the involved sites, and the presence of inflammatory changes.

Objective: To identify the clinical features that can help to distinguish between psoriatic arthritis (PsA) and fibromyalgia (FM)., Methods: Our cross-sectional study was carried out in 10 Italian rheumatology centers between January and September 2009, and enrolled all consecutive patients with PsA and FM who agreed to participate. Standard clinical and laboratory data for PsA and FM were collected from all patients. Records were made of somatic symptoms, response to nonsteroidal antiinflammatory drugs (NSAID), self-evaluated pain, general health, disability, and responses to the Fibromyalgia Impact Questionnaire. Data were statistically analyzed by univariate and multivariate analyses, and receiver-operating characteristic curves. The analysis concentrated on the clinical features shared by the 2 conditions., Results: Two hundred sixty-six patients with PsA (mean age 51.7 yrs; disease duration 10.2 yrs) and 120 patients with FM (mean age 50.2 yrs; disease duration 5.6 yrs) were evaluated. Univariate analysis showed that patients with FM had higher mean tender point and enthesitis scores, more somatic symptoms, and responded less to NSAID. Multivariate analysis showed that the presence of ≥ 6 FM-associated symptoms and ≥ 8 tender points was the best predictor of FM., Conclusion: The shared clinical features of PsA and FM that had the greatest discriminating power for FM were the number of FM-associated symptoms and tender point count.

Objective: The purpose of this study was to evaluate the long-term survival rate of Methotrexate (MTX) in the peripheral joint involvement of psoriatic arthritis (PsA) in a setting of everyday clinical practice., Methods: This was an observational restrospective study performed using the data from a dermatological-rheumatological PsA clinic. All of the patients evaluated at this clinic from March 1997 to December 2007 who were started on MTX alone, had a three-year follow-up time or had discontinued the therapy were included into the survey., Results: Of the 174 evaluable patients, 104 (59.8%) were still taking MTX after three years of treatment. The reasons of therapy discontinuation in the remaining 70 (40.2%) patients were: 34 (19.5%) lost-to-follow-up, 18 (10.3%) adverse events, 14 (8%) inefficacies, and 4 (2.3%) deaths (none related to the therapy). MTX was effective in controlling joint inflammation but not in preventing their deterioration. Overall, adverse events were recorded in 43 patients (36.4% of the 114 patients with a three-year follow-up). No serious side effect occurred in the study population., Conclusions: The results of this study showed that, in a setting of clinical pratice, MTX had a good three-year performance in patients with peripheral PsA. Almost 60% of them were still taking this drug at the end of the study period and the toxicity was more than acceptable. In our opinion, MTX might be considered the non-biological DMARD of choice for the treatment of this condition. However it should be used earlier and at higher doses.

The authors have examined two homogeneous groups of patients suffering from "carotid stenosis", operated by TEAC with two different techniques of anaesthesia: general and local-regional (block). Neurological and cardiovascular complications have been recorded in pre and post-operative period. The results analysed statistically with the Pearson test, were homogeneous. However the authors, on the basis of their experience, prefer local-regional (block) anaesthesia for good haemodynamic stability and a better neurologic control. Moreover the block anaesthesia was better in patients.