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Background and purpose: The importance of upper limb function in multiple sclerosis (MS) is increasingly recognized, especially for the evaluation of patients with progressive MS with reduced mobility. Two sensor‐engineered gloves, able to measure quantitatively the timing of finger opposition movements, were previously used to assess upper limb disability in MS. The aims of the present study were: (1) to confirm the association between glove‐derived variables and standard measures of MS disability in a larger cohort; (2) to assess the correlation with quantitative magnetic resonance imaging (MRI) and quality of life (QoL) measures; and (3) to determine if the glove‐derived variables offer advantages over the standard measure for assessing upper limb function in MS, namely, the Nine‐Hole Peg Test (9HPT). Methods: Sixty‐five patients with MS, stable on disease‐modifying treatment, were evaluated at baseline using the glove, and through clinical examination (Expanded Disability Status Scale, Symbol Digit Modalities Test, Timed 25‐Foot Walk Test and 9HPT), MRI evaluation and QoL questionnaires. Correlations between the glove‐derived variables and clinical, MRI and QoL variables were assessed using Spearman's rank correlation coefficient analysis. Results: Glove‐derived variables significantly differed between patients with relapsing‐remitting and those with progressive MS, with similar or slightly higher correlations of the 9HPT with clinical variables. We found greater correlations of the QoL physical component with glove‐derived variables than with the 9HPT, and a significant correlation of its mental component with the glove‐derived variables but not with the 9HPT. Conclusion: The study results, confirming previous findings and showing advantages over the 9HPT, encourage the investigation of sensitivity to change in glove‐derived variables in a longitudinal setting. [ABSTRACT FROM AUTHOR]

Objective The aim of this observational study was to investigate the evolution of scleroderma microangiopathy throughout different nailfold videocapillaroscopy (NVC) patterns ('early', 'active', 'late') as well as the prevalence of organ involvement in SSc patients during a 12-year follow-up. Methods Thirty-four SSc patients showing at baseline (first capillaroscopic analysis) the 'early' NVC pattern of microangiopathy were enrolled and followed for 12 years (s. d. 2). Complete NVC analysis and clinical and serological findings were collected. Patients were in a standard therapeutic care setting. Statistical analysis was carried out by non-parametric tests. Results After a 12-year follow-up, the 'early' NVC pattern changed from baseline in 76% of the patients. The NVC pattern was found to be 'active' in 9 patients (26%), 'late' in 13 (38%) and characterized by non-specific capillary abnormalities in 4 (12%). In the subgroup whose microangiopathy progressed from the 'early' to the 'late' NVC pattern, the median time of progression from the 'early' to the 'active' pattern was significantly shorter (11 months) when compared with patients who progressed from the 'early' to the 'active' NVC pattern (55 months) (P = 0.002). The median time of progression between NVC patterns was significantly shorter in SSc patients showing either a nucleolar ANA pattern or Scl70 autoantibodies (P = 0.048). Organ involvement was progressively greater in SSc patients with 'early', 'active' and 'late' NVC patterns, respectively. Conclusions This longitudinal study confirms over a 12-year follow-up the evolution of specific NVC patterns associated with the progressive severity of organ involvement in SSc patients in a standard clinical care setting. [ABSTRACT FROM AUTHOR]

• Multiple sclerosis patients have exacerbated the Covid-19 infection similarly to the general population in the Turkish MS & Covid-19 cohort. • Immunomodulatory treatments used in the treatment of multiple sclerosis are not related to the severity of Covid-19 infection. • High age, high EDSS, and having a progressive MS type are risk factors for severe Covid-19 infection. • Young age and low comorbidity caused an overall mild course of Covid-19 infection in the Turkish MS population. The pandemic of the new type of corona virus infection 2019 [Covid-19] also affect people with Multiple Sclerosis (pwMS). Currently, the accumulating information on the effects of the infection regarding the demographic and clinical characteristics of the disease, as well as outcomes within different DMTs¸ enable us to have better practices on the management of the Covid-19 infection in pwMS. To investigate the incidence of coronavirus disease 2019 (Covid-19) and to reveal the relationship between the demographic-clinical and therapeutic features and the outcome of Covid-19 infection in a multi-center national cohort of pwMS. The Turkish Neurological Society-MS Study Group in association with the Italian MuSC-19 Study Group initiated this study. A web-based electronic Case Report Form (eCRF) of Study-MuSC-19 were used to collect the data. The demographic data and MS histories of the patients were obtained from the file tracking forms of the relevant clinics. 309 MS patients with confirmed Covid-19 infection were included in this study. Two hundred nineteen (219) were females (70.9%). The mean age was 36.9, ranging from 18 to 66, 194 of them (62.8%) were under 40. The clinical phenotype was relapsing-remitting in 277 (89.6%) and progressive in 32 (10.4%). Disease duration ranged from 0.2 years to 31.4 years. The median EDSS was 1.5, ranging from 0 to 8.5. The EDSS score was<= 1 in 134 (43%) of the patients. 91.6% of the patients were on a DMT, Fingolimod was the most frequently used drug (22.0%), followed by Interferon (20.1%). The comorbidity rate is 11.7%. We were not able to detect any significant association of DMTs with Covid-19 severity. The Turkish MS-Covid-19 cohort had confirmed that pwMS are not at risk of having a more severe COVID-19 outcome irrespective of the DMT that they are treated. In addition, due to being a younger population with less comorbidities most had a mild disease further highlight that the only associated risk factors for having a moderate to severe COVID-19 course are similar with the general population such as having comorbid conditions and being older. [ABSTRACT FROM AUTHOR]

Dear Editor, Dermatoscopy has proven more accurate than naked-eye examination,[1] and sequential digital dermatoscopic imaging (SDDI) superior to dermatoscopy alone for melanoma detection.[2] SDDI combined with total-body photography (TBP),[3] namely the "two-step method" of digital follow-up (DFU), seems at present the best surveillance strategy for high-risk patients.[[4]] Short-term follow-up is optimal for single melanocytic lesions, but long-term follow-up is better for monitoring multiple lesions in high-risk patients.[[5], [7]] TBP contributed to a lesser extent to melanoma detection. Benefits of total body photography and digital dermatoscopy ("two-step method of digital follow-up") in the early diagnosis of melanoma in patients at high risk for melanoma. [Extracted from the article]

• A survey study on lifestyle/dietary habits of a cohort with multiple sclerosis (MS). • A snapshot of mostly proactive MS adult women, incline to healthy behaviors. • Mediterranean Diet (MeDi) may modulate abdominal adiposity but not Body Mass Index. • MeDi may be a strategy to control cardiovascular risk and Expanded Disability Status Scale. • A dietary pattern's study provides a more realistic analysis of interdependent foods. Several studies supported the beneficial effects of the Mediterranean diet (MeDi) on chronic diseases. In Multiple Sclerosis (MS), the MeDi might interfere with systemic inflammatory state, gut microbiota, and comorbidities. The Med Diet Score (MDS) estimates the adherence to the MeDi and the cardiovascular (CV) risk. Aims of our study were i) to photograph lifestyle and diet habits of a southern Italy cohort of people with MS (pwMS), and ii) to investigate the impact of the MeDi on MS clinical outcomes. We conducted a multi-center, cross-sectional study, enrolling 435 consecutive consenting pwMS, attending the outpatient clinics for routine follow-up visits. Participants underwent a clinical examination and a 29-item self-administered questionnaire on life and dietary habits. Disease phenotype, Expanded Disability Status Scale (EDSS), MS Severity Score (MSSS), waist circumference (WC), Body Mass Index (BMI), therapies, and comorbidities, were updated. MDS was assessed and correlated with current and retrospective clinical data. 75.8% of respondents were interested in nutrition, 72.8% were non-smokers, 52.9% performed physical activity, and 45.6% used food supplements. MDS was higher in pwMS with normal WC (p = 0.031), and inversely correlated with MSSS (p = 0.013) and EDSS (p = 0.012) at survey time. MDS did not correlate with the total number of relapses (before and after diagnosis) (p = 0.372). Metabolic comorbidities were associated with an increased 10-year CV risk (r = 0.85, p = 0.002). Our findings suggest a putative beneficial effect of the MeDi on WC, MS course and disability. Given the role of chronic systemic inflammation in maintenance of autoimmunity and secondary neurodegeneration, both involved in long-term disability, we may suppose a beneficial effect of the MeDi on MS long-term disability outcomes, probably mediated by a modulation of the gut microbiota and the low-grade chronic systemic inflammation. [ABSTRACT FROM AUTHOR]

Unspecific bone uptake (UBU) related to [ 18 F]PSMA-1007 PET/CT imaging represents a clinical challenge. We aimed to assess whether a combination of clinical, biochemical, and imaging parameters could predict skeletal metastases in patients with [ 18 F]PSMA-1007 bone focal uptake, aiding in result interpretation. Methods: We retrospectively analyzed [ 18 F]PSMA-1007 PET/CT performed in hormone-sensitive prostate cancer (PCa) patients at 3 tertiary-level cancer centers. A fourth center was involved in performing an external validation. For each, a volume of interest was drawn using a threshold method to extract SUV max , SUV mean , PSMA tumor volume, and total lesion PSMA. The same volume of interest was applied to CT images to calculate the mean Hounsfield units (HU mean ) and maximum Hounsfield units. Clinical and laboratory data were collected from electronic medical records. A composite reference standard, including follow-up histopathology, biochemistry, and imaging data, was used to distinguish between PCa bone metastases and UBU. PET readers with less ( n = 2) or more ( n = 2) experience, masked to the reference standard, were asked to visually rate a subset of focal bone uptake ( n = 178) as PCa metastases or not. Results: In total, 448 bone [ 18 F]PSMA-1007 focal uptake specimens were identified in 267 PCa patients. Of the 448 uptake samples, 188 (41.9%) corresponded to PCa metastases. Ongoing androgen deprivation therapy at PET/CT ( P < 0.001) with determination of SUV max ( P < 0.001) and HU mean ( P < 0.001) independently predicted bone metastases. A composite prediction score, the bone uptake metastatic probability (BUMP) score, achieving an area under the receiver-operating-characteristic curve (AUC) of 0.87, was validated through a 10-fold internal and external validation ( n = 89 bone uptake, 51% metastatic; AUC, 0.92). The BUMP score's AUC was significantly higher than that of HU mean (AUC, 0.62) and remained high among lesions with HU mean in the first tertile (AUC, 0.80). A decision-curve analysis showed a higher net benefit with the score. Compared with the visual assessment, the BUMP score provided added value in terms of specificity in less-experienced PET readers (88% vs. 54%, P < 0.001). Conclusion: The BUMP score accurately distinguished UBU from bone metastases in PCa patients with [ 18 F]PSMA-1007 focal bone uptake at PET imaging, offering additional value compared with the simple assessment of the osteoblastic CT correlate. Its use could help clinicians interpret imaging results, particularly those with less experience, potentially reducing the risk of patient overstaging., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Aims: To investigate the relationship between chronic low-grade inflammation, as measured by high-sensitivity C-reactive protein (hsCRP) levels, and incident heart failure (HF) or cancer., Methods and Results: We assessed the relationship between baseline hsCRP concentrations and subsequent HF or cancer in two community-based cohorts, the Trøndelag Health Study (HUNT3) and the Health, Aging and Body Composition (ABC) study. In the latter, the analysis was replicated with interleukin (IL)-1, IL-6, or tumour necrosis factor (TNF)-α instead of hsCRP. In HUNT3, hsCRP was measured in 47 163 subjects (mean age 52.3 ± 15.8 years). During a median follow-up of 12.1 years, 2034 (4.3%) individuals developed HF and 5024 (10.7%) cancer, with 442 (0.9%) being diagnosed with both. After adjusting for age, male sex, diabetes, obesity, previous or current smoking, and comorbidities, elevated baseline hsCRP was associated with a higher risk of HF or cancer [hazard ratio (HR) 1.09; 95% confidence interval (CI), 1.07-1.10]. In the Health ABC study, hsCRP levels were assessed in 2803 participants, who had a mean age of 72.6 ± 2.9 years and a higher burden of comorbidities than in HUNT3. During a median follow-up of 8.2 years, HF and cancer were diagnosed in 346 (12.3%) and 776 (27.7%) subjects, respectively, with 77 (2.7%) having both conditions. After adjusting for the same variables used for the HUNT3 cohort, hsCRP remained significantly associated with incident HF or cancer (HR 1.11; 95% CI, 1.05-1.18), as were IL-1 (HR 1.15; 1.07-1.24), IL-6 (HR 1.09; 1.02-1.17), and TNF-α (HR 1.15; 1.07-1.24)., Conclusion: A state of chronic, low-grade inflammation captured by an increase in hsCRP levels is associated with an increased risk of developing HF or cancer, with potential implications for clinical trials with anti-inflammatory therapies., Competing Interests: Conflict of interest: C.J. is an employee of NordicRWE AS, both unrelated to the present work. C.J. received personal fees from MSD and is an employee of NordicRWE AS, both unrelated to the present work. J.B. received personal fees from Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Roche, and Vifor, all unrelated to the present work. C.M. received personal fees from Amgen, AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Bristol Myers Squibb, Edwards, Novartis, Novo Nordisk, Pharmacosmos, and Servier, all unrelated to the present work. P.A. received personal fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Janssen, MSD, and Novartis, all unrelated to the present work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset., Methods: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05., Results: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor-positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p < .001), hormone receptor-positive (p < .001), and node-positive (p = .003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p < .001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64-0.95) and overall survival (HR, 0.65; 95% CI, 0.46-0.93) in the TN subgroup. Luminal A-like tumors in HER2-low (p = .014) and TN and luminal A-like in HER2-0 (p = .019) showed the worst DFS., Conclusions: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: The lack of standardized disability progression evaluation in multiple sclerosis (MS) hinders reproducibility of clinical study results, due to heterogeneous and poorly reported criteria., Objective: To demonstrate the impact of using different parameters when evaluating MS progression, and to introduce an automated tool for reproducible outcome computation., Methods: Re-analyzing BRAVO clinical trial data (NCT00605215), we examined the fluctuations in computed treatment effect on confirmed disability progression (CDP) and progression independent of relapse activity (PIRA) when varying different parameters. These analyses were conducted using the msprog package for R, which we developed as a tool for CDP assessment from longitudinal data, given a set of criteria that can be specified by the user., Results: The BRAVO study reported a hazard ratio (HR) of 0.69 (95% confidence interval (CI): 0.46-1.02) for CDP. Using the different parameter configurations, the resulting treatment effect on CDP varied considerably, with HRs ranging from 0.59 (95% CI: 0.41-0.86) to 0.72 (95% CI: 0.48-1.07). The treatment effect on PIRA varied from an HR = 0.62 (95% CI: 0.41-0.93) to an HR = 0.65 (95% CI: 0.40-1.04)., Conclusions: The adoption of an open-access tool validated by the research community, with clear parameter specification and standardized output, could greatly reduce heterogeneity in CDP estimation and promote repeatability of study results., Competing Interests: Declaration of Conflicting InterestsMaria Pia Sormani has received personal compensation for consulting services and for speaking activities from Merck, Novartis, Roche, Sanofi, Bristol-Meyer Squibb, Immunic and Biogen. The other author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Seminal vesicle involvement (SVI) in patients with newly diagnosed prostate cancer is associated with high rates of treatment failure and tumor recurrence; correct identification of SVI allows for effective management decisions and surgical planning., Methods: This single-center retrospective study analyzed MR images of the seminal vesicles from patients undergoing radical prostatectomy with confirmed T3b disease, comparing them to a control group without SVI matched for age and Gleason grade with a final stage of T2 or T3a. Seminal vesicles were segmented by an experienced uroradiologist, "raw" and bladder-normalized T2 signal intensity, as well as SV volume, were obtained., Results: Among the 82 patients with SVI, 34 (41.6%) had unilateral invasion, and 48 (58.4%) had bilateral disease. There was no statistically significant difference in the degree of distension between normal and involved seminal vesicles (P = 0.08). Similarly, no statistically significant difference was identified in the raw SV T2 signal intensity (P = 0.09) between the groups. In the 159 patients analyzed, SVI was prospectively suspected in 10 of 82 patients (specificity, 100%; sensitivity, 12.2%). In all these cases, lesions macroscopically invaded the seminal vesicle, and the raw T2 signal intensity was significantly lower than that in the SVI and control groups (P = 0.02 and 0.01)., Conclusion: While signal intensity measurements in T2-weighted images may provide insight into T3b disease, our findings suggest that this data alone is insufficient to reliably predict SVI, indicating the need for further investigation and complementary diagnostic approaches., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: No biomarkers are currently available to predict therapeutic response to ustekinumab (UST) in Crohn's disease (CD). The aim of this prospective study was to identify 1 or more cytokines able to predict mucosal healing in patients with CD treated with UST., Methods: We prospectively enrolled consecutive CD patients treated with UST. At weeks 0 (baseline), 24, and 48, a panel of serum cytokines was measured by a fluorescence assay. At the same time points, fecal calprotectin (FC) was assessed. A colonoscopy was performed at baseline and at week 48, where therapeutic outcome was evaluated in terms of mucosal healing., Results: Out of 44 patients enrolled, 22 (50%) achieved mucosal healing at the end of follow-up. Response was associated with higher interleukin (IL)-23 levels (P < .01). Fecal calprotectin levels decreased over time in responders but did not change in nonresponders (test for the interaction between time and mucosal healing, P < .001)., Conclusions: This pilot study showed that IL-23 and FC could be reliable biomarkers in predicting therapeutic outcome to UST therapy in CD. In particular, the correlation between baseline serum levels of IL-23 and mucosal healing at 48 weeks is particularly strong, paving the way for its use to drive therapeutic decisions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Intermediate clinical endpoints (ICEs) are frequently used as primary endpoint in randomised trials (RCTs). We aim to assess whether changes in different ICEs can be used to predict changes in overall survival (OS) in adjuvant breast cancer trials., Methods: Individual patient level data from adjuvant phase III RCTs conducted by the Gruppo Italiano Mammella (GIM) and Mammella Intergruppo (MIG) study groups were used. ICEs were computed according to STEEP criteria. Using a two-stage meta-analytic model, we assessed the surrogacy of each ICE at both the outcome (i.e., OS and ICE are correlated irrespective of treatment) and trial (i.e., treatment effects on ICE and treatment effect on OS are correlated) levels. The following ICEs were considered as potential surrogate endpoints of OS: disease-free survival (DFS), distant disease-free survival (DDFS), distant relapse-free survival (DRFS), recurrence-free survival (RFS), recurrence-free interval (RFI), distant recurrence-free interval (DRFI), breast cancer-free interval (BCFI), and invasive breast cancer-free survival (IBCFS). The estimates of the degree of correlation were obtained by copula models and weighted linear regression. Kendall's τ and R 2  ≥ 0.70 were considered as indicators of a clinically relevant surrogacy., Findings: Among the 12,397 patients enrolled from November 1992 to July 2012 in six RCTs, median age at enrolment was 57 years (interquartile range (IQR) 49-65). After a median follow-up of 10.3 years (IQR 6.4-14.5), 2131 (17.2%) OS events were observed, with 1390 (65.2%) attributed to breast cancer. At the outcome-level, Kendall's τ ranged from 0.69 for BCFI to 0.84 for DRFS. For DFS, DDFS, DRFS, RFS, RFI, DRFI, BCFI, and IBCFS endpoints, over 95% of the 8-year OS variability was attributable to the variation of the 5-year ICE. At the trial-level, treatment effects for the different ICEs and OS were strongly correlated, with the highest correlation for RFS and DRFS and the lowest for BCFI., Interpretation: Our results provide evidence supporting the use of DFS, DDFS, DRFS, RFS, RFI, DRFI, and IBCFS as primary endpoint in breast cancer adjuvant trials., Funding: This analysis was supported by the Italian Association for Cancer Research ("Associazione Italiana per la Ricerca sul Cancro", AIRC; IG 2017/20760) and by Italian Ministry of Health-5 × 1000 funds (years 2021-2022)., Competing Interests: Eva Blondeaux reports research support (to the Institution) from Gilead outside the submitted work. Wanling Xie served as consultant to Convergent Therapeutics, Inc outside the submitted work. Carmine De Angelis reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Daicii-Sankyo, Gilead, and GSK and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Seagen, GSK, GILEAD, and Daiichi-Sankio. Travel Grants from Gilead and research support (to the Institution) from Novartis, GILEAD, and Daiichi-Sankyo outside the submitted work. Fabio Puglisi reports honoraria for advisory boards, activities as a speaker, travel grants, research grants from Amgen–Astrazeneca–Daiichi Sankyo–Celgene–Eisai–Eli Lilly-–Exact Sciences- Gilead–Ipsen—Menarini- MSD–Novartis–Pierre Fabre–Pfizer–Roche–Seagen–Takeda—Viatris and research funding from Astrazeneca—Eisai—Roche outside the submitted work. Mauro Mansutti reports honoraria for advisory boards, activities as a speaker, travel grants: Accord Healthcare, Amgen, Astra Zeneca, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Seagen outside the submitted work. Alessandra Fabi reports advisory board from Roche, Novartis, Lilly, Pfizer, MSD, Pierre Fabre, Eisai, Epionpharma, Gilead, Seagen, Astra Zeneca, Exact Science and consultant from Dompè Farnaceutica outside the submitted work. Matteo Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Knight and Takeda, Travel Grants from Gilead and Daiichi Sankyo, and research support (to the Institution) from Gilead outside the submitted work. Lucia Del Mastro reports grants or contracts from Eli Lilly, Novartis, Roche, Daiichi Sankyo, and Seagan; honoraria from Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Sciences, and Ipsen; support for attending meetings or travel from Roche, Pfizer, and Eisai; participation on a Data Safety Monitoring Board or Advisory Board from Novartis, Roche, Eli Lilly, Pfizer, Daiichi Sankyo, Exact Sciences, Gilead, Pierre Fabre, Eisai, and AstraZeneca outside the submitted work. Meredith M Regan reports consulting or advisory role for Ipsen (to the Institution), Tolmar, Bristol Myers Squibb, Debiopharm Group (to the Institution), TerSera, AstraZeneca and research funding from Pfizer (to the Institution), Ipsen (to the Institution), Novartis (to the Institution), Merck (to the Institution), AstraZeneca (to the Institution), Pierre Fabre (to the Institution), Bayer (to the Institution), Bristol Myers Squibb (to the Institution), Roche (to the Institution), TerSera (to the Institution), Debiopharm Group (to the Institution), BioTheranostics (to the Institution) and honoraria from Bristol Myers Squibb and Canadian Urological Association., (© 2024 The Author(s).)

Anterior Visual Pathway (aVP) damage may be linked to diverse inflammatory, degenerative and/or vascular conditions. Currently however, a standardized methodological framework for extracting MRI biomarkers of the aVP is not available. We used high-resolution, 3-D MRI data to generate a probabilistic anatomical atlas of the normal aVP and its intraorbital (iOrb), intracanalicular (iCan), intracranial (iCran), optic chiasm (OC), and tract (OT) subdivisions. We acquired 0.6 mm 3 steady-state free-precession images from 24 healthy participants using a 3 T scanner. aVP masks were obtained by manual segmentation of each aVP subdivision. Mask straightening and normalization with cross-sectional area (CSA) preservation were obtained using scripts developed in-house. A probabilistic atlas ("aVP-24") was generated by averaging left and right sides of all subjects. Leave-one-out cross-validation with respect to interindividual variability was performed employing the Dice Similarity Index (DSI). Spatially normalized representations of the aVP subdivisions were generated. Overlapping CSA values before and after normalization demonstrate preservation of the aVP cross-section. Volume, length, CSA, and ellipticity index (ε) biometrics were extracted. The aVP-24 morphology followed previous descriptions from the gross anatomy. Atlas spatial validation DSI scores of 0.85 in 50% and 0.77 in 95% of participants indicated good generalizability across the subjects. The proposed MRI standardization framework allows for previously unavailable, geometrically unbiased biometric data of the entire aVP and provides the base for future spatial-resolved, group-level investigations., (© 2024. The Author(s).)

The presence of sarcopenia has been associated with the worst outcome of Crohn's disease (CD). At present, no studies have evaluated the impact of ustekinumab (UST) in terms of its effects on body composition. The aim of this prospective study was to evaluate whether UST treatment could modify the parameters of body composition as assessed by bioelectrical impedance assay (BIA) in patients with CD. We prospectively enrolled consecutive patients with CD treated with UST, evaluating the therapeutic outcome at week 48 in terms of clinical remission and mucosal healing. BIA was performed at baseline and at week 48, assessing body cellular mass, total body water, phase angle, and body mass index. Out of 44 patients enrolled, 26 (59%) were in clinical remission and 22 (50%) achieved mucosal healing at the end of follow up. No significant differences were observed at baseline in all the BIA parameters between responders and non-responders. Phase angle increased over time in responders, while this was not observed in non-responders (test for the interaction between time and outcome, p -value = 0.009 and 0.007 for clinical remission and mucosal healing, respectively). The same differential increase was observed for body cellular mass (test for the interaction between time and outcome, p -value = 0.03 and 0.05 for clinical remission and mucosal healing, respectively). Total body water and BMI increased homogenously over time regardless of the outcomes (tests for the association with time, p -values of 0.01). To conclude, responsiveness to UST therapy seems to be associated with body composition modifications in patients with CD. In particular, the increase in phase angle in responders suggests that a significant improvement of nutritional status occurred in these patients.

Background: Optic pathway is considered an ideal model to study the interaction between inflammation and neurodegeneration in multiple sclerosis (MS)., Methods: Optical Coherence Tomography (OCT) and 3.0 T magnetic resonance imaging (MRI) were acquired in 92 relapsing remitting (RR) MS at clinical onset. Peripapillary RNFL (pRNFL) and macular layers were measured. White matter (WM) and gray matter (GM) lesion volumes (LV), lateral geniculate nucleus (LGN) volume, optic radiations (OR) WM LV, thickness of pericalcarine cortex were evaluated. OCT and MRI control groups (healthy controls [HC]-OCT and HC-MRI) were included., Results: A significant thinning of temporal pRNFL and papillo-macular bundle (PMB) was observed (p<0.001) in 16 (17%) patients presented with monocular optic neuritis (MSON+), compared to 76 MSON- and 30 HC (-15 μm). In MSON-, PMB was reduced (-3 μm) compared to HC OCT (p<0.05). INL total volume was increased both in MSON+ (p<0.001) and MSON- (p = 0.033). Inner retinal layers volumes (macular RNFL, GCL and IPL) were significantly decreased in MSON+ compared to HC (p<0.001) and MSON- (p<0.001). Reduced GCL volume in the parafoveal ring was observed in MSON- compared to HCOCT (p < 0.05). LGN volume was significantly reduced only in MSON+ patients compared to HC-MRI (p<0.001) and MSON- (p<0.007). GCL, IPL and GCIP volumes associated with ipsilateral LGN volume in MSON+ and MSON-. Finally, LGN volume associated with visual cortex thickness with no significant difference between MSON+ and MSON-., Conclusions: Anterograde trans-synaptic degeneration is early detectable in RRMS presenting with optic neuritis but does not involve LGN., Competing Interests: Declaration of Competing Interest M.S., M.A., C.L., Mo.M., S.P., Pe.M., S.E., D.M., F.S., B.A. have no conflict to disclose. Ma.M. reports grants and personal fees from Almiral. She was awarded a MAGNIMS-ECTRIMS fellowship in 2020. Pu.M. reports grants from Almirall, Teva, Sanofi Genzyme, Merck Serono, Biogen Italy, Novartis, consultancy for Novartis, Biogen Italy, and Sanofi. G.P. reports grants from Almirall, Teva, Sanofi Genzyme, Merck Serono, Biogen Italy, Novartis, Roche, Bristol Myers Squibb; consultancy for Novartis, Biogen Italy, Sanofi Genzyme, Roche, Bristol Myers Squibb; board membership Sanofi Genzyme, Novartis, Biogen Italy, Roche, Merck Serono, Bristol Myers Squibb., (Copyright © 2023. Published by Elsevier B.V.)

Oncoplastic breast-conserving surgery (OBCS) is increasingly used to treat breast cancer with the dual purpose of performing a radical oncological resection while minimizing the risk of post-operative deformities. The aim of the study was to evaluate the patient outcomes after Level II OBCS as regards oncological safety and patient satisfaction. Between 2015 and 2020, a cohort of 109 women consecutively underwent treatment for breast cancer with bilateral oncoplastic breast-conserving volume displacement surgery; patient satisfaction was measured with BREAST-Q questionnaire. The 5-year overall survival and disease-free survival were 97% (95%CI 92, 100) and 94% (95%CI 90, 99), respectively. In two patients (1.8%), mastectomy was finally performed due to margin involvement. The median patient-reported score for "satisfaction with breast" (BREAST-Q) was 74/100. Factors associated with a lower aesthetic satisfaction index included: location of tumour in central quadrant (p = 0.007); triple negative breast cancer (p = 0.045), and re-intervention (p = 0.044). OBCS represents a valid option in terms of oncological outcomes for patients otherwise candidate to more extensive breast conserving surgery; the high satisfaction index also suggests a superiority in terms of aesthetic outcomes., (© 2023. The Author(s).)

Background: Vulvar lichen sclerosus (LS) severely impairs patients' quality of life., Objectives: To evaluate the impact of a combined application of autologous platelet-rich plasma (PRP) and fat grafting as treatment for vulvar LS on patient quality of life., Materials & Methods: We reviewed the clinical charts of 72 patients affected by LS, who underwent regenerative surgery. The patients' quality of life was assessed using: the Dermatology Life Quality Index (DLQI), the Skindex-29, the Female Sexual Function Index (FSFI) and the patient-administered - Clinical Scoring System (CSS)., Results: After reconstructive surgery, all scores improved: Skindex-29 (-31.8 [IQR: 42.1, -21.8] points; p<0.001), FSFI (7.6 [IQR: 2.7, 14.7)] points; p<0.001), Patient-administered CSS (-24 [IQR: -30, -15] points; p<0.001), DLQI (-9 [IQR: -17, -7] points; p<0.001), Physician-administered CSS (-5 [IQR: -7, -5] points; p<0.001), and IGA (median ΔIGA: -4, IQR: -4, -3; p<0.001)., Conclusion: Combined treatment with PRP and fat grafting proved to be effective in improving the quality of life of patients with vulvar LS.

MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, especially in non-acute phases and when serologic testing for MOG antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin 4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of patients with MOG-antibody disease in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included. Data collection and analyses were conducted from 2019 to 2021. Inclusion criteria were: diagnosis of MOG-antibody disease; AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis; brain and cord MRI at least 6 months from relapse; and Expanded Disability Status Scale (EDSS) score on the day of MRI. Brain white matter T2 lesions, T1-hypointense lesions, cortical and cord lesions were identified. Random forest models were constructed to classify patients as MOG-antibody disease/AQP4-neuromyelitis optica spectrum disorder/multiple sclerosis; a leave one out cross-validation procedure assessed the performance of the models. Based on the best discriminators between diseases, we proposed a guide to target investigations for MOG-antibody disease. One hundred and sixty-two patients with MOG-antibody disease [99 females, mean age: 41 (±14) years, median EDSS: 2 (0-7.5)], 162 with AQP4-neuromyelitis optica spectrum disorder [132 females, mean age: 51 (±14) years, median EDSS: 3.5 (0-8)], 189 with multiple sclerosis (132 females, mean age: 40 (±10) years, median EDSS: 2 (0-8)] and 152 healthy controls (91 females) were studied. In young patients (<34 years), with low disability (EDSS < 3), the absence of Dawson's fingers, temporal lobe lesions and longitudinally extensive lesions in the cervical cord pointed towards a diagnosis of MOG-antibody disease instead of the other two diseases (accuracy: 76%, sensitivity: 81%, specificity: 84%, P < 0.001). In these non-acute patients, the number of brain lesions < 6 predicted MOG-antibody disease versus multiple sclerosis (accuracy: 83%, sensitivity: 82%, specificity: 83%, P < 0.001). An EDSS < 3 and the absence of longitudinally extensive lesions in the cervical cord predicted MOG-antibody disease versus AQP4-neuromyelitis optica spectrum disorder (accuracy: 76%, sensitivity: 89%, specificity: 62%, P < 0.001). A workflow with sequential tests and supporting features is proposed to guide better identification of patients with MOG-antibody disease. Adult patients with non-acute MOG-antibody disease showed distinctive clinical and MRI features when compared to AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis. A careful inspection of the morphology of brain and cord lesions together with clinical information can guide further analyses towards the diagnosis of MOG-antibody disease in clinical practice., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Language is usually considered the social vehicle of thought in intersubjective communications. However, the relationship between language and high-order cognition seems to evade this canonical and unidirectional description (ie, the notion of language as a simple means of thought communication). In recent years, clinical high at-risk mental state (CHARMS) criteria (evolved from the Ultra-High-Risk paradigm) and the introduction of the Clinical Staging system have been proposed to address the dynamicity of early psychopathology. At the same time, natural language processing (NLP) techniques have greatly evolved and have been successfully applied to investigate different neuropsychiatric conditions. The combination of at-risk mental state paradigm, clinical staging system and automated NLP methods, the latter applied on spoken language transcripts, could represent a useful and convenient approach to the problem of early psychopathological distress within a transdiagnostic risk paradigm., Methods and Analysis: Help-seeking young people presenting psychological distress (CHARMS+/- and Clinical Stage 1a or 1b; target sample size for both groups n=90) will be assessed through several psychometric tools and multiple speech analyses during an observational period of 1-year, in the context of an Italian multicentric study. Subjects will be enrolled in different contexts: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa-IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Mental Health Department-territorial mental services (ASL 3-Genoa), Genoa, Italy; and Mental Health Department-territorial mental services (AUSL-Piacenza), Piacenza, Italy. The conversion rate to full-blown psychopathology (CS 2) will be evaluated over 2 years of clinical observation, to further confirm the predictive and discriminative value of CHARMS criteria and to verify the possibility of enriching them with several linguistic features, derived from a fine-grained automated linguistic analysis of speech., Ethics and Dissemination: The methodology described in this study adheres to ethical principles as formulated in the Declaration of Helsinki and is compatible with International Conference on Harmonization (ICH)-good clinical practice. The research protocol was reviewed and approved by two different ethics committees (CER Liguria approval code: 591/2020-id.10993; Comitato Etico dell'Area Vasta Emilia Nord approval code: 2022/0071963). Participants will provide their written informed consent prior to study enrolment and parental consent will be needed in the case of participants aged less than 18 years old. Experimental results will be carefully shared through publication in peer-reviewed journals, to ensure proper data reproducibility., Trial Registration Number: DOI:10.17605/OSF.IO/BQZTN., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Haploidentical stem cell transplantation is a viable strategy in the absence of an HLA-identical donor, but in myelofibrosis (MF), concerns may rise due to the risk of graft failure. Considering that engraftment is a major issue in MF, we sought to highlight its impact on survival outcomes. In addition, we explored the impact of pretransplantation ruxolitinib administration as an independent variable on outcomes. Here we report the results of a retrospective, monocentric experience with T cell-replete haploidentical bone marrow transplantation with post-transplantation cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis in 51 consecutive MF-affected patients. The median duration of follow-up was 47 months. All 51 patients received a double-alkylating conditioning regimen, and 21 patients (41%) received pretransplantation ruxolitinib. Thirty-seven of 49 evaluable patients (76%) achieved full donor chimerism with neutrophil engraftment, 8 of 49 (16%) experienced graft rejection, and 4 of 49 (8%) had primary poor graft function. Splenectomy was more frequent among patients who engrafted (P = .06). Graft rejection was the sole factor negatively impacting overall survival (hazard ratio [HR], 4.19; 95% confidence interval [CI], 1.37 to 12.80; P = .01) and the major determinant for nonrelapse mortality (HR, 10.31; 95% CI, 2.54 to 41.82; P = .001). The 24-month incidence of relapse was 19% and was negatively impacted by splenectomy (HR, 5.84; 95% CI, 1.28 to 26.72; P = .02). The cumulative incidence of grade II-IV acute GVHD was 27% (95% CI, 20% to 33%), and that of grade III-IV acute GVHD was 8% (95% CI, 4% to 12%). The 24-month cumulative incidence of all-grade chronic GVHD was 28% (95% CI, 21% to 35%). Our data show that T cell-replete haploidentical bone marrow transplantation following double-alkylating conditioning in patients with MF is associated with favorable rates of GVHD and an acceptable relapse risk; nevertheless, rejection is not negligible and is associated with significant mortality. Splenectomy, which favors engraftment, is predictive of a higher risk of relapse., Competing Interests: Conflict of interest statement: There are no conflicts of interest to report Authorship statement: M.G. and S.B. contributed equally to this work., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Many studies investigated the association between air pollution and Covid-19 severity but the only study focusing on patients with Multiple Sclerosis (MS) exclusively evaluated exposure to PM2.5. We aim to study, in a sample of MS patients, the impact of long-term exposure to PM2.5, PM10 and NO2 on Covid-19 severity, described as occurrence of pneumonia., Methods: A 1:2 ratio case-control study was designed, differentiating cases and controls based on Covid-19 pneumonia. Associations between pollutants and outcome were studied using logistic regression. Weighted quantile sum (WQS) logistic regression was used to identify the individual contribution of each pollutant within the mixture; Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression was performed to confirm the variable selection from WQS. All the analyses were adjusted for confounders selected a priori., Results: Of the 615 eligible patients, 491 patients provided detailed place of exposure and were included in the principal analysis. Higher concentrations of air pollutants were associated with increased odds of developing Covid-19 pneumonia (PM2.5: 3rd vs 1st tercile OR(95% CI)=2.26(1.29;3.96); PM10: 3rd vs 1st tercile OR(95% CI)=2.12(1.22;3.68); NO2: 3rd vs 1st tercile OR(95% CI)=2.12(1.21;3.69)). Pollutants were highly correlated with each other; WQS index was associated to an increased risk of pneumonia (β=0.44; p-value=0.004) and the main contributors to this association were NO2 (41%) and PM2.5 (34%). Consistently, Lasso method selected PM2.5 and NO2., Conclusions: Higher long-term exposure to PM2.5, PM10 and NO2 increased the odds of Covid-19 pneumonia among MS patients and the most dangerous pollutants were NO2 and PM2.5., Competing Interests: Declaration of Competing Interest Sormani MP received consulting fees from Roche, Biogen, Merck, Novartis, Sanofi, Celgene, Immunic, Geneuro, GSK, Medday; received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Roche, Biogen Merck, Novartis, Sanofi, Celgene; participated on a Data Safety Monitoring Board or Advisory Board for Roche, Sanofi, Novartis, Merck. Caleri F received honoraria for lectures or presentation from Biogen, Merck, Teva, Novartis, Sanofi-Genzyme, Roche; received support for attending meeting and travel grant from Biogen, Merck, Teva, Novartis, Sanofi-Genzyme, Roche; received honoraria for participation on Advisory Boards from Biogen, Merck, Teva, Novartis, Sanofi-Genzyme, Roche. Cordioli C received grants or contracts from Roche, Novartis, Merck Serono, Biogen, Celgene; received consulting fees from Biogen. Inglese M received grants or contracts from FISM, INAIL, European Union. Salvetti M received grants or contracts from Biogen, Merck, Novartis; received payments or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Biogen, Merck, Novartis, Roche, Sanofi. R. Bergamaschi has served on scientific advisory boards for Biogen, Merck‐Serono, Novartis, Sanofi‐Genzyme; received research support from Almirall, Bayer, Biogen, Merck‐Serono, Novartis, Sanofi‐Genzyme; received support for travel and congress from Biogen, Roche, Merck‐Serono, Sanofi‐Genzyme, Teva; received honoraria for speaking engagements from Biogen, Merck‐Serono, Novartis, Sanofi‐Genzyme. M. Filippi is Editor‐in‐Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Associate Editor of Radiology and Associate Editor of Neurological Sciences; received compensation for consulting services and/or speaking activities from Alexion, Almirall, Bayer, Biogen, Celgene, Eli Lilly, Genzyme, Merck‐Serono, Novartis, Roche, Sanofi, Takeda and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck‐Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla and ARiSLA (Fondazione Italiana di Ricerca per la SLA). He received speaker honoraria from the following companies: Biogen, Merck, Novartis, Roche, Sanofi‐Genzyme and TEVA. M. Radaelli received speaker honoraria from Biogen Idec, Sanofi‐Genzyme, Novartis and Merck Serono and funding for travel to scientific meetings from Biogen Idec, Sanofi‐Genzyme, Novartis, Merck Serono, Teva and Roche. P. Immovilli reports personal fees from Roche, personal fees from Biogen, personal fees from Merck, outside the submitted work. V. Brescia Morra has received funding for travel, speaker honoraria, advisory board and research support from Merck Serono, Novartis, Biogen Idec, TEVA, Genzyme, Roche, Bayer, Almirall. G. Comi reports personal fees from Novartis, Teva Pharmaceutical Industries Ltd, Teva Italia Srl, Sanofi Genzyme, Genzyme Corporation, Genzyme Europe, Merck KGaA, Merck Serono SpA, Celgene Group, Biogen Idec, Biogen Italia Srl, F. Hoffman‐La Roche, Roche SpA, Almirall SpA, Forward Pharma, Medday, Excemed, outside the submitted work. F. Patti reports grants from Biogen, grants from Merck, grants from FISM, grants from Onlus association, grants from University of Catania, personal fees from Almirall, personal fees from Bayer, personal fees from Biogen, personal fees from Merck, personal fees from Roche, personal fees from Sanofi, personal fees from TEVA, outside the submitted work., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Purpose: Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation., Method: Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number., Results: From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p = 0.005) and more in smoker patients (OR 1.39; p = 0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p = 0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p = 0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p = 0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p = 0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p = 0.024), joint or muscle pain (G2, p = 0.013) and ageusia and anosmia (G5, p &lt; 0.001). All cases should be referred to variants up to Delta., Conclusion: Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID-19 symptoms., (© 2022 European Academy of Neurology.)

Background: Psoriasis is associated with multiple comorbidities, including cardiovascular disease. Identifying biomarkers such as N-terminal fragment of the BNP precursor (NT-pro-BNP) with preventive, diagnostic, and prognostic implications in the cardiovascular diseases of psoriatic patients may be helpful in these patient's management. However, their predictive ability for future cardiovascular events in psoriatic patients is still unknown. Therefore, the study aimed to determine whether NT-pro-BNP levels were increased in psoriatic patients., Methods: One hundred forty psoriatic patients without cardiovascular disease and 140 healthy control patients were enrolled., Results: The NT-pro-BNP level was significantly correlated with lipid profile but not with disease duration; or the ongoing biologic therapy., Conclusions: Our work demonstrates that pro-BNP values are higher in patients with psoriasis than in controls and emphasizes the correlation between psoriasis and cardiovascular disease and the importance of biomarkers that can identify those patients most at risk of developing cardiovascular disease.

We described nailfold videocapillaroscopy (NVC) findings and estimated the prevalence of serum anti-nuclear (ANA) and extractable nuclear antigen autoantibodies (ENA) in a cohort of sarcoidosis patients, comparing them with adequate healthy controls (HCs) and with primary Raynaud's phenomenon patients (PRPs). NVC findings were also correlated with the occurrence of autoantibodies, current treatment, laboratory parameters, variables of lung function and whole-body imaging data. Twenty-six patients with sarcoidosis were assessed through NVC, laboratory parameters, pulmonary function tests, chest-X ray and 18- fluorodeoxyglucose positron emission tomography/computed tomography. The NVC parameters and ANA/ENA dosage were recorded also in 30 PRPs and 30 HCs. Sarcoidosis patients showed a higher rate of capillary dilations and nonspecific abnormalities and a lower mean capillary absolute number than PRPs and HCs (p < 0.01 for all comparisons). The prevalence of ANA positivity was higher in patients with sarcoidosis compared with PRPs and HCs (p < 0.02 for both), whereas ENA positivity was detected in one sarcoidosis patient (Ro52). Among sarcoidosis patients, the mean capillary absolute number negatively correlated with the C-reactive protein concentrations and was positively associated with the forced vital capacity percentage. Instead, a negative correlation was detected between serum ACE levels and the presence of capillary dilations (all p < 0.05). Our findings suggest a microvascular involvement in sarcoidosis whose investigation by NVC might be useful for the follow-up of patients displaying RP. Autoantibody positivity in sarcoidosis might suggest autoimmune implications in the disease or the production of autoantibodies reactive to tissue damage., (© 2022. The Author(s).)

Objective: To determine the effect of geriatric comanagement on clinical outcomes of older patients undergoing surgery for gastrointestinal cancer., Design: This was a single-center, nonrandomized, before-and-after study, which compared patient outcomes before and after the implementation of geriatric comanagement in an oncological surgery division., Setting and Participants: The study included patients aged 70 or older, who were treated for a gastrointestinal cancer at the Oncological Surgery Division of the Policlinico San Martino Hospital (Genoa, Italy). Patients from the control group were treated between January 2015 and October 2018, and the patients who received geriatric comanagement during their stay in the surgical ward were treated between November 2018 and December 2019., Methods: Patients from both groups received a preoperative comprehensive geriatric assessment in the preoperative phase and were followed according to the Enhanced Recovery After Surgery model in the perioperative period. In the geriatric comanagement group, targeted interventions during daily geriatrician-led ward rounds were performed. Inverse probability weighting was used to adjust estimates for potential baseline confounders., Results: A total of 207 patients were included: 107 in the control group and 90 who received geriatric comanagement. Overall, patients from both groups had similar demographic and clinical characteristics with a median [interquartile range (IQR)] age of 80.0 (77.0, 84.0) years and a pre-frail phenotype [median (IQR) 40-item Frailty Index 0.15 (0.10, 0.26)]. In the geriatric comanagement group, a significant reduction in grade I-V complications (adjusted odds ratio 0.29; 95% CI 0.21-0.40); P &lt; .001) and in 1-year readmissions (adjusted hazard ratio 0.53; 95% CI 0.28-0.98; P &lt; .044) was observed. No difference between the 2 groups in terms of 1-year mortality was detected., Conclusions and Implications: Our study supports the implementation of geriatric comanagement in the care of older patients undergoing surgery for gastrointestinal cancer., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

This study aimed to compare adalimumab originator vs. biosimilar in HS patients, and to evaluate the effect of a switch to a biosimilar, or a switch back to the originator, in terms of treatment ineffectiveness. Patients with a diagnosis of HS were enrolled from 14 Italian sites. Treatment ineffectiveness was measured using Hurley score. The major analyses were 1) comparison between the two treatment groups (non-switcher analysis), and 2) the cross-over trend of Hurley score between treatment switchers (switcher analysis). Cox and Poisson regression models were used to compare the treatment ineffectiveness between groups. A total of 326 patients were divided into four groups: 171 (52.5%) taking originator; 61 (18.7%) patients taking biosimilar; 66 (20.2%) switchers; 28 (8.6%) switchers from originator to biosimilar and switched. A greater loss of efficacy was observed in the group allocated to the biosimilar than the originator group. The switcher analysis showed an effectiveness loss in the biosimilar compared to the originator. These results seem to indicate that a switch from one drug to the other may lead to a greater risk of inefficacy. A return to the previous treatment also does not ensure efficaciousness.

Background: Nailfold videocapillaroscopy (NVC) non-specific abnormalities may be present in subjects with isolated Raynaud's phenomenon (RP) before the potential transition to systemic sclerosis (SSc) specific microvascular alterations ('scleroderma pattern'). This study aims to investigate NVC non-specific abnormalities, notably capillary dilations, in RP patients, as possible forerunners of the 'scleroderma pattern'., Methods: A 10-year retrospective NVC-based investigation evaluated 55 RP patients sorted into 3 sex-matched and age-matched groups according to clinical evolution: 18 later developing SSc (cases), 19 later developing other connective tissue disease and 18 maintaining primary RP at long-term follow-up (controls). All patients had a basal NVC showing non-specific abnormalities, namely non-specific &gt;30 µm dilated capillaries (30-50 μm diameter). Sequential NVCs were longitudinally evaluated using current standardised approach. Statistical analysis assessed the risk for developing a 'scleroderma pattern'., Results: Significantly larger capillary diameters were observed in cases versus controls both at basal NVC and during follow-up NVC (p=&lt;0.05 to &lt;0.001). Interestingly, controls showed stable NVC non-specific abnormalities over the study follow-up. The number of &gt;30 µm dilated capillaries/mm at basal NVC was the strongest single predictor of 'scleroderma pattern' evolution with 24% increased risk per each dilated capillary (OR 1.24, 95% CI 1.17,1.32). Additionally, a tree-based analysis suggested the efferent (venous) diameter of the most dilated capillary on basal NVCas a variable of interest to identify patients maintaining primary RP., Conclusion: This is the first study to describe an NVC 'prescleroderma signature' to potentially identify RP patients later developing a 'scleroderma pattern'., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A eucaloric very low carbohydrate diet (EVLCD) is a diet with a daily caloric intake equal to the total daily energy expenditure (TDEE) with a carbohydrate content of <50 g/day. The literature on very low carbohydrate diets (VLCD) in type 1 diabetes (DM 1) is limited, although recently published scientific studies have highlighted their safety and efficacy in managing DM 1. In this retrospective analysis, we report the clinical data of 33 patients affected by DM 1 carrying out insulin therapy who switched voluntarily from their usual diet (high carb, low fat) to an EVLCD. Our aim is to evaluate the glycemic control, the amount of insulin needed in order to maintain glycemic control and safety of EVLCD. The switch improved glycemic control (mean glycated hemoglobin decreased from 8.3% to 6.8% (p < 0.01). The number of patients who reached a glycated hemoglobin value of <7% increased statistically from 12% to 57% (p < 0.01), and there was a statistically significant decrease (p < 0.01) in the units of daily insulin (from 36.7± 14.9 IU to 28.9 ±9.1 IU) A reduction from 54% to 24% in clinical level 2 hypoglycemia episodes was reported. No cases of severe hypoglycemia or ketoacidosis were observed. The results of the study support that EVLCD in DM 1 seems safe and effective when adopted under tight medical supervision.

Introduction: Raynaud phenomenon (RP), typically, precede the clinical onset of systemic manifestations in several connective tissue diseases (CTDs). These autoimmune disorders usually share a microvascular damage whose alterations can be detected by nailfold videocapillaroscopy (NVC). The aim of the study was to compare the NVC microvascular status in Mixed Connective Tissue Disease (MCTD) versus the Undifferentiated Connective Tissue Disease (UCTD), and to search correlations between NVC findings and specific autoantibodies in UCTD patients., Methods: Clinical data and NCV patterns were retrospectively obtained from the files of 46 MCTD patients, 47 stable UCTD patients and 51 individuals with primary RP (PRP) as controls collected in a central database (VideoCap®, DS Medica, Milan, Italy). ANA and ENA Abs were tested respectively by indirect immunofluorescence and enzyme-linked immunosorbent assay., Results: "Scleroderma-like" (SSc-like) NVC pattern was significantly more frequent in MCTD than in UCTD patients (48% vs 11%, p < 0.001). Giant capillaries, abnormal shapes (i.e. neoangiogenesis) and lower capillary density were predominantly detected among MCTD versus UCTD patients (48% vs 11%, 49% vs 13%, 52% vs 9%, respectively, p < 0.001). The absolute number of capillaries was significantly lower in MCTD versus UCTD patients (mean 7 ± 1.7 SD vs mean 9.2 ± 1.3 SD, respectively, p < 0.001). Fully normal NVC pattern and non-specific NVC alterations were respectively observed in 6% and 46% of MCTD and in 6% and 83% of UCTD. Moreover, PRP patients showed normal NVC pattern and non-specific capillary abnormalities in 23% and in 77%, respectively. No statistically significant correlations were observed between NVC patterns and ANA patterns/specific ENA-Abs among the UCTD patients., Conclusions: The significant presence of the SSc-like NVC pattern and reduced number of capillaries seem the most typical NVC findings in MCTD in comparison to UCTD patients, suggesting a reflection of more complex and severe disease in MCTD ones., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Many risk factors for the development of severe forms of Covid-19 have been identified, some applying to the general population and others specific to Multiple Sclerosis (MS) patients. However, a score for quantifying the individual risk of severe Covid-19 in patients with MS is not available. The aim of this study was to construct such score and to evaluate its performance., Methods: Data on patients with MS infected with Covid-19 in Italy, Turkey and South America were extracted from the Musc-19 platform. After imputation of missing values, data were separated into training data set (70%) and validation data set (30%). Univariable logistic regression models were performed in the training dataset to identify the main risk factors to be included in the multivariable logistic regression analyses. To select the most relevant variables we applied three different approaches: (1) multivariable stepwise, (2) Lasso regression, (3) Bayesian model averaging. Three scores were defined as the linear combination of the coefficients estimated in the models multiplied by the corresponding value of the variables and higher scores were associated to higher risk of severe Covid-19 course. The performances of the three scores were compared in the validation dataset based on the area under the ROC curve (AUC) and an optimal cut-off was calculated in the training dataset for the score with the best performance. The probability of showing a severe Covid-19 course was calculated based on the score with the best performance., Results: 3852 patients were included in the study (2696 in the training dataset and 1156 in the validation data set). 17% of the patients required hospitalization and risk factors for severe Covid-19 course were older age, male sex, living in Turkey or South America instead of living in Italy, presence of comorbidities, progressive MS, longer disease duration, higher Expanded Disability Status Scale, Methylprednisolone use and anti-CD20 treatment. The score with the best performance was the one derived using the Lasso selection approach (AUC= 0.72) and it was built with the following variables: age, sex, country, BMI, presence of comorbidities, EDSS, methylprednisolone use, treatment. An excel spreadsheet to calculate the score and the probability of severe Covid-19 is available at the following link: https://osf.io/ac47u/?view&#95;only=691814d57b564a34b3596e4fcdcf8580., Conclusions: The originality of this study consists in building a useful tool to quantify the individual risk for Covid-19 severity based on patient's characteristics. Due to the modest predictive ability and to the need of external validation, this tool is not ready for being fully used in clinical practice to make important decisions or interventions. However, it can be used as an additional instrument to identify high-risk patients and persuade them to take important measures to prevent Covid-19 infection (i.e. getting vaccinated against Covid-19, adhering to social distancing, and using of personal protection equipment)., (Copyright © 2022. Published by Elsevier B.V.)

Background and Purpose: We hypothesized that 3D T1-TSE "black-blood" images may carry an increased risk of contrast-enhancing lesion misdiagnosis in patients with MS because of the misinterpretation of intraparenchymal vein enhancement. Thus, the occurrence of true-positive and false-positive findings was compared between standard MPRAGE and volumetric interpolated brain examination techniques., Materials and Methods: Sampling perfection with application-optimized contrasts by using different flip-angle evolution (SPACE) images obtained from 232 patients with MS, clinically isolated syndrome, or radiologically isolated syndrome were compared with standard MPRAGE and volumetric interpolated brain examination images. The intraparenchymal vein contrast-to-noise ratio was estimated at the level of the thalami. Contrast-enhancing lesions were blindly detected by 2 expert readers and 1 beginner reader. True- and false-positives were determined by senior readers' consensus. True-positive and false-positive frequency differences and patient-level diagnosis probability were tested with the McNemar test and OR. The contrast-to-noise ratio and morphology were compared using the Mann-Whitney U and χ 2 tests., Results: The intraparenchymal vein contrast-to-noise ratio was higher in SPACE than in MPRAGE and volumetric interpolated brain examination images ( P < .001, both). There were 66 true-positives and 74 false-positives overall. SPACE detected more true-positive and false-positive results ( P range < .001-.07) but did not increase the patient's true-positive likelihood (OR = 1 1.29, P = .478-1). However, the false-positive likelihood was increased (OR = 3.03-3.55, P = .008-.027). Venous-origin false-positives ( n = 59) with contrast-to-noise ratio and morphology features similar to small-sized (≤14 mm 3 P = .544) true-positives occurred more frequently in SPACE images ( P < .001)., Conclusions: Small intraparenchymal veins may confound the diagnosis of enhancing lesions on postgadolinium black-blood SPACE images., (© 2022 by American Journal of Neuroradiology.)

Background: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in patients with MS (pwMS) under different DMTs and to identify correlates of reduced protection., Methods: This is a prospective Italian multicenter cohort study, long-term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) study. 1855 pwMS scheduled for SARS-CoV-2 mRNA vaccination were enrolled and followed up to a mean time of 10 months. The cumulative incidence of breakthrough Covid-19 cases in pwMS was calculated before and after December 2021, to separate the Delta from the Omicron waves and to account for the advent of the third vaccine dose., Findings: 1705 pwMS received 2 m-RNA vaccine doses, 21/28 days apart. Of them, 1508 (88.5%) had blood assessment 4 weeks after the second vaccine dose and 1154/1266 (92%) received the third dose after a mean interval of 210 days (range 90-342 days) after the second dose. During follow-up, 131 breakthrough Covid-19 infections (33 during the Delta and 98 during the Omicron wave) were observed. The probability to be infected during the Delta wave was associated with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.57, p < 0.001); the protective role of antibodies was preserved over the whole follow up (HR=0.57, 95%CI=0.43-0.75, p < 0.001), with a significant reduction (HR=1.40, 95%CI=1.01-1.94, p=0.04) for the Omicron cases. The third dose significantly reduced the risk of infection (HR=0.44, 95%CI=0.21-0.90,p=0.025) during the Omicron wave., Interpretation: The risk of breakthrough SARS-CoV-2 infections is mainly associated with reduced levels of the virus-specific humoral immune response., Funding: Supported by FISM - Fondazione Italiana Sclerosi Multipla - cod. 2021/Special-Multi/001 and financed or co-financed with the '5 per mille' public funding., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available., Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test., Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model., Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p  = 0.002)., Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.

Background: Microvascular remodeling is one major responsible for vascular adaptation in pregnancy, still it is not routinely evaluated in the obstetric field. This pilot study aimed to explore the role of nailfold capillaroscopy (NCV) in detecting microvascular changes during normal pregnancy., Methods: A population of 30 healthy pregnant women was longitudinally followed performing clinical assessment and NVC evaluation at each trimester and post-partum. Thirty non-pregnant age-matched healthy women having received at least two NVCs with a minimum 9 to 12-month interval were selected as controls. All NVC images were evaluated by a qualitative and semi-quantitative assessment using current standardised approach. Statistical analyses were conducted to assess NVC trend throughout gestation and its possible association with pregnancy course., Results: A progressive significant increase of NVC neoangiogenesis and a specular reduction in capillary dilations was observed during pregnancy (p < 0.05). These variations were not found in age-matched controls, who showed stable NVC parameters over a similar time frame (p < 0.05). Additionally, a significant inverse correlation was found between NVC neoangiogenesis rate and maternal systemic BP (rho = -0.72, p < 0.005)., Conclusion: This first comprehensive longitudinal NVC evaluation during normal pregnancy reports significant but physiological microvascular variations throughout gestation, suggesting NVC as a safe and promising technique for further investigate and define patterns of microvascular changes also in pathological pregnancies., (Copyright © 2022. Published by Elsevier Inc.)