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Abstract Background Primary Sjögren Syndrome is a rare autoimmune systemic disease characterized by impaired secretory functions of the exocrine gland. One of the main clinical features is dry mouth and subsequent oral diseases, which are also found in patients with Sicca. This leads to a marked deterioration in the quality of life and the patient’s search for information and solutions. Many patients turn to patients’ associations that offer moments of sharing to their members, especially through online discussion forums. Today, these forums represent quality material for a sociological or biomedical analysis of patients' concerns, as close as possible to their daily lives. Our objective is to analyze the concerns of patients with SS or Sicca regarding their dry mouth especially dental care. Methods In this cross-sectional observation study, a quantitative analysis of the Mouth-Nose online forum discussion of the French Association of Patients with Gougerot-Sjögren’s Syndromes and Dryness have been performed. After reading and re-reading, initial request themes, topics, and subtopics were established and coding was performed. Then, the 885 threads were classified depending the initial request, pragma-linguistic indices and the main topic discussed in the thread. After identifying the threads dealing with dental care, we looked at which types of care were most discussed and classified the discussions according to whether or not the patient was satisfied with their care at the dentist. Results The majority of the initial requests are posts for experiences sharing and/or advice. The topic of “dental care” is one of the main concerns of the forum users. Among the threads that concern dental care, requests to share experience with implants are in the majority. Finally, the majority of the posts on dental care relate to care in private dental practice, deals with dental implants and prevention and resulted mainly in patient satisfaction. Conclusions Analysis of the forum reveals importance of patient concerns about prevention, and care costs due to implant treatment, which add to disease burden. Most of messages relate favorable experiences with their dentists, which is in line with the approach of sharing experiences and support characteristic of a forum.

Not available.

CD38-targeting immunotherapy is approved in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM) that are transplant ineligible (TI) and is considered the best standard of care (SOC). To improve current SOC, we evaluated the added value of weekly bortezomib (V) to isatuximab plus lenalidomide and dexamethasone (IsaRd versus Isa-VRd). This Intergroupe Francophone of Myeloma phase 3 study randomized 270 patients with NDMM that were TI, aged 65-79 years, to IsaRd versus Isa-VRd arms. The primary endpoint was a minimal residual disease (MRD) negativity rate at 10 -5 by next-generation sequencing at 18 months from randomization. Key secondary endpoints included response rates, MRD assessment rates, survival and safety. The 18-month MRD negativity rates at 10 -5 were reported in 35 patients (26%, 95% confidence interval (CI) 19-34) in IsaRd versus 71 (53%, 95% CI 44-61) in Isa-VRd (odds ratio for MRD negativity 3.16, 95% CI 1.89-5.28, P < 0.0001). The MRD benefit was consistent across subgroups at 10 -5 and 10 -6 , and was already observed at month 12. The proportion of patients with complete response or better at 18 months was higher with Isa-VRd (58% versus 33%; P < 0.0001), as was the proportion of MRD negativity and complete response or better (37% versus 17%; P = 0.0003). At a median follow-up of 23.5 months, no difference was observed for survival times (immature data). The addition of weekly bortezomib did not significantly affect the relative dose intensity of IsaRd. Isa-VRd significantly increased MRD endpoints, including the 18-month negativity rate at 10 -5 , the primary endpoint, compared with IsaRd. This study proposes Isa-VRd as a new SOC for patients with NDMM that are TI. ClinicalTrials.gov identifier: NCT04751877 ., (© 2024. The Author(s).)

Multiple myeloma (MM) frequently causes vertebral fractures (VF). Some are lytic lesions and others have the aspect of benign osteoporotic fractures not requiring anti-myeloma treatment. We explored outcome of these patients with smoldering myeloma (SM) and osteoporotic VF. In this retrospective bi-centric study, patients were identified using a systematic keyword search on electronic medical records. Patients with SM and isolated VF of osteoporotic aspect without indications for myeloma-specific therapy were included. Overall, 13 (7 %) of the 184 identified patients had SM and VF confirmed to be osteoporotic (median number of VF was 3). During follow-up, 12 (92 %) patients evolved to symptomatic MM, 7 (54 %) of them within 18 months (early progressors). Myeloma defining events were new lytic bone lesions in 7 patients (53.8 %). The serum calcium level was significantly higher in the early progressor group (median 2.35 IQR [2.31-2.38] and 2.28 IQR [2.21-2.29] respectively, p  = 0.003). Early progressors had a higher number of VF at diagnosis (3.0 [2.0-5.5] vs 1.0 [1.0-2.5], p  = 0.18) and more frequently evolved to symptomatic MM because of lytic bone lesions (5 [71 %] vs 2 [33 %], p  = 0.13) compared to late progressors. VF of osteoporotic appearance in the context of SM is a rare situation but at high risk of rapid progression to symptomatic MM, suggesting that they may represent bone fragility linked to MM infiltration rather than solely osteoporotic fractures. Further studies are needed to assess if earlier treatment might be beneficial in this population., Competing Interests: KC has no conflict of interest. SH has no conflict of interest. SB has received grant from SERVIER, unrelated to his work. JH has no conflict of interest. KB has Honoria and research grant from Amgen, Theramex, and Kyowa Kirin, unrelated to his work. RB has received Honoria from Astra Zaneca, unrelated to his work. RC has received Honoria and research grant from ALEXION and research grant from REGENRON, unrelated to his work. XM has received Honoria from BMS, Galapagos, GSK, Novartis, Pfizer, unrelated to his work. RS received consulting fees or honoraria from GSK, Bristol Myer Squib, Boehringer, Janssen, Amgen, Pfizer and Roche, travel fees from Amgen and GSK, unrelated to his work., (© 2024 The Authors.)

Belantamab mafodotin (BM) is an anti-BCMA antibody-drug conjugate (GSK2857916) that represents an alternative option in multiple myeloma. We sought to assess the efficacy and safety of BM in a real-world setting in patients who benefited from an early access program. We conducted an observational, retrospective, multicenter study. Eligibility criteria were treatment of relapsed or refractory multiple myeloma (RRMM) in monotherapy in adult patients who have received at least three lines of therapy previously, including at least one immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody, and whose disease progressed during the last treatment period. The primary endpoint of the study is to assess the overall survival (OS). Between November 2019 and December 2020, 106 patients were treated with BM; 97 were eligible for the efficacy evaluation and 104 for safety. The median age was 66 (range, 37-82) years. High-risk cytogenetics were identified in 40.9% of patients. Fifty-five (56.7%) patients were triple-class refractory and 11 (11.3%) were penta-class refractory. The median number of prior lines of treatment was five (range, 3-12). The median number of BM cycles administered was three (range, 1-22). The overall response rate at best response was 38.1% (37/97). The median OS was 9.3 months (95% confidence interval [CI]: 5.9-15.3), and median progression-free survival was 3.5 months (95% CI: 1.9-4.7). The median duration of response was 9 months (range, 4.65-10.4). Treatment was delayed for 55 (52.9%) patients including 36.5% for treatment-related toxicity. Ophthalmic adverse events, mainly grade ≤2, were the most common toxicity (48%). The occurrence of keratopathy was 37.5%. Overall, our data are concordant with the results from DREAMM-2 in terms of efficacy and safety on a non-biased population.

Objective: There is limited experience regarding the use of biological disease-modifying antirheumatic drug (bDMARD) and JAK inhibitor (JAKi) for the management of immune checkpoint inhibitors (ICI)-induced inflammatory arthritis. We aimed to assess their efficacy and safety in this setting., Methods: Using the Club Rhumatismes and Inflammation French network, we conducted a multicentre, retrospective, observational study of patients with cancer diagnosed with inflammatory arthritis under ICI(s) and treated with bDMARD or JAKi. Clinical data were collected using a standardised case report form., Results: Twenty patients (60% men, median age 69.5 years) were included, with rheumatoid arthritis (RA)-like (n=16), polymyalgia rheumatica-like (n=2) or psoriatic arthritis-like (n=2) clinical presentation. Two patients had pre-existing RA. 90% were treated with glucocorticoids as first-line therapy and 60% received methotrexate prior to bDMARD or JAKi. Anti-interleukin-6 receptor (IL-6R) therapy was used in 13/20 patients (65%), leading to clinical improvement in 11/13 patients (85%), but one patient experienced intestinal perforation and cancer progression was noticed in 6/13 patients (46%). Tumour necrosis factor inhibitors were used in 5/20 patients (25%), with improvement in 4/5 patients (80%) and cancer progression was observed in 3/5 patients (60%). Two infections (diverticulitis and pneumonitis) were reported. Anakinra, baricitinib and ustekinumab were each used in one patient. Median duration of the bDMARD or JAKi was 17 weeks., Conclusion: Anti-IL-6R therapy is currently the most common strategy in patients with ICI-induced inflammatory arthritis and insufficient response to glucocorticoids and methotrexate, leading to improvement in &gt;80%. Overall, cancer progression occurred in about half of patients and whether the bDMARD/JAKi impacted the tumour response remains to be determined., 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.)

Background: Primary Sjögren Syndrome is a rare autoimmune systemic disease characterized by impaired secretory functions of the exocrine gland. One of the main clinical features is dry mouth and subsequent oral diseases, which are also found in patients with Sicca. This leads to a marked deterioration in the quality of life and the patient's search for information and solutions. Many patients turn to patients' associations that offer moments of sharing to their members, especially through online discussion forums. Today, these forums represent quality material for a sociological or biomedical analysis of patients' concerns, as close as possible to their daily lives. Our objective is to analyze the concerns of patients with SS or Sicca regarding their dry mouth especially dental care., Methods: In this cross-sectional observation study, a quantitative analysis of the Mouth-Nose online forum discussion of the French Association of Patients with Gougerot-Sjögren's Syndromes and Dryness have been performed. After reading and re-reading, initial request themes, topics, and subtopics were established and coding was performed. Then, the 885 threads were classified depending the initial request, pragma-linguistic indices and the main topic discussed in the thread. After identifying the threads dealing with dental care, we looked at which types of care were most discussed and classified the discussions according to whether or not the patient was satisfied with their care at the dentist., Results: The majority of the initial requests are posts for experiences sharing and/or advice. The topic of "dental care" is one of the main concerns of the forum users. Among the threads that concern dental care, requests to share experience with implants are in the majority. Finally, the majority of the posts on dental care relate to care in private dental practice, deals with dental implants and prevention and resulted mainly in patient satisfaction., Conclusions: Analysis of the forum reveals importance of patient concerns about prevention, and care costs due to implant treatment, which add to disease burden. Most of messages relate favorable experiences with their dentists, which is in line with the approach of sharing experiences and support characteristic of a forum., (© 2022. The Author(s).)

Objective: Antibody response to the messenger RNA (mRNA) COVID-19 vaccine has been shown to be diminished in rituximab (RTX)-treated patients. We undertook this study to compare humoral and T cell responses between healthy controls, patients with autoimmune diseases treated with RTX, and those treated with other immunosuppressants, all of whom had been vaccinated with 2 doses of the mRNA COVID-19 vaccine., Methods: We performed anti-spike IgG and neutralization assays just before and 28 days after the second BNT162b2 (Pfizer-BioNTech) vaccine dose. The specific T cell response was assessed in activated CD4 and CD8 T cells using intracellular flow cytometry staining of cytokines (interferon-γ, tumor necrosis factor, and interleukin-2) after stimulation with SARS-CoV-2 spike peptide pools., Results: A lower proportion of responders with neutralizing antibodies to the vaccine was observed in the RTX group (29%; n = 24) compared to the other immunosuppressants group (80%; n = 35) (P = 0.0001) and the healthy control group (92%; n = 26) (P < 0.0001). No patients treated with RTX in the last 6 months showed a response. Time since last infusion was the main factor influencing humoral response in RTX-treated patients. The functional CD4 and CD8 cellular responses to SARS-CoV-2 peptides for each single cytokine or polyfunctionality were not different in the RTX group compared to the other immunosuppressants group or the control group. In RTX-treated patients, the T cell response was not different between patients with and those without a humoral response., Conclusion: RTX induced a diminished antibody response to the mRNA COVID-19 vaccine, but the functional T cell response was not altered compared to healthy controls and autoimmune disease patients treated with other immunosuppressants. Further work is needed to assess the clinical protection granted by a functionally active T cell response in the absence of an anti-spike antibody response., (© 2021 American College of Rheumatology.)

Objectives: Peripheral ulcerative keratitis (PUK) is a severe corneal condition associated with uncontrolled RA. Tocilizumab (TCZ) is used to control RA, however, episodes of paradoxical ocular inflammation have been reported in TCZ-treated patients. We report a case series of PUK in TCZ-treated RA patients with ophthalmological and systemic findings and discuss the potential underlying mechanisms., Methods: Four patients (six eyes), 47-62 years of age, were included. At the onset of PUK, the median duration of RA was 13 years [interquartile range (IQR) 3-13] and the median treatment with TCZ was 9 months (IQR 3-14). Two patients had active disease [28-joint DAS (DAS28) >3.2] and the disease was controlled in two patients (DAS28 ≤3.2)., Results: TCZ was initially replaced by another immunomodulatory treatment in all patients and later reintroduced in two patients without PUK recurrence. Corneal inflammation was controlled in all cases with local and systemic treatments, with severe visual loss in one eye., Conclusion: PUK may occur in patients with long-standing RA after a switch to TCZ and can be interpreted, depending on the context, as insufficient efficacy or a paradoxical manifestation. These cases highlight the urgent need for reliable biomarkers of the efficacy and paradoxical reactions of biologics., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To study the characteristics of B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence., Methods: A multicentre case-control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma., Results: 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma., Conclusion: Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA., Competing Interests: Competing interests: PD: participation to clinical trials and punctual interventions for BMS and Roche. CM: reports outside the submitted work personal fees from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Sanofi. PG: honoraria from AbbVie, Amgen, Biogaran, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, MEDAC, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, UCB. BF: research grants from AbbVie, Lilly, MSD and Pfizer, and honoraria from AbbVie, Amgen, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, SanofiAventis, SOBI, UCB. PP: participation in clinical trials and punctual honoraria from MSD Pfizer ABBvie Sanofi Novartis Sandoz. BC: honoraria from AbbVie, BMS, Gilead, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer, RocheChugai and research grants from Novartis, Pfizer, and Roche. GN: received honorarium from Novartis, Lilly and UCB. RS: received honorarium from Pfizer, BMS and UCB. XM: received honorarium from BMS, Gilead, Pfizer, UCB., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the relevance of salivary gland ultrasound (SGUS) and its place in the diagnostic algorithm in patients referred with dry syndrome (DS) for a suspicion of Sjögren's syndrome (SS)., Methods: We included all patients assessed at our dedicated DS clinic from June 2015 to September 2019 for which a SGUS has been carried out. Images were read blindly and the worst salivary gland was scored according to OMERACT classification. Clinical features, disease activity and treatments were collected., Results: 337 patients were seen from June 2015 to September 2019. 269 patients underwent SGUS. 77 patients were diagnosed with SS and 192 did not meet the ACR/EULAR criteria for SS: non-Sjögren's DS (NSDS). Of these 192 patients, 60 had another possible cause of DS, and 132 patients were diagnosed with SAPS (sicca, asthenia, polyalgia syndrome).SGUS abnormalities were significantly higher in patients with SS versus NSDS: 51% vs 8% for a score ≥2 (p<0.0001), and 43% vs 3% for a score ≥3 (p<0.0001). SGUS score ≥2 had a specificity (Sp) of 91%, sensitivity (Se) of 57%, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 82% for SS diagnosis. SGUS's characteristics in SSA-negative patients were similar to the whole population (Se=42%, Sp=91%, PPV=42%, NPV=92%). The high specificity and NPV in this population could avoid labial salivary gland biopsy (LSGB) in SSA-negative patients with normal SGUS (186 patients, 69%)., Conclusion: SGUS is useful for SS diagnosis. If anti-SSA antibodies are negative and SGUS score <2, the diagnosis of SS is very improbable and LSGB could be avoided., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The frequency and consequences of anti-drug antibodies to rituximab (RTX-ADA) are not well known in RA and even less in other systemic auto-immune diseases (sAID). We aimed to evaluate the frequency, consequences and predictive factors of RTX-ADA in RA and sAID., Methods: All patients presenting with RA or other sAID treated with RTX from 2012 to 2017 in our tertiary reference centre for sAID were retrospectively studied. Patients who were tested for RTX-ADA were identified., Results: One hundred and ninety-nine patients were treated with RTX (RA: 124, other sAID: 75). Among 62/199 (31.1%) tested for RTX-ADA, 14 were positive: 3/35 RA (8.6%) and 11/27 (40.7%) other sAID, (P = 0.0047). Among the whole RTX-treated populations, the frequency of RTX-ADA was 2.4% and 14.7% (P = 0.0026) in RA and sAID, respectively. Most of the immunized patients had infusion reactions to second or subsequent RTX cycles (11/14) and loss of efficacy (2/14). Predictive factors of immunization were sAID vs RA (78.6% vs 21.4%, P = 0.026, adjusted odds ratio (OR) = 5.35[1.43-54.75]) and African ethnicity (57.1% vs 4.2%, P < 0.001, adjusted OR = 9.25 [5.08-302.12]). Associated immunosuppressive therapy did not protect against immunization. Three patients with pSS immunized against RTX were treated with ofatumumab with complete remission of their disease., Conclusion: Immunization against RTX is more frequent in other sAID than in RA. Testing for RTX-ADA must be performed in patients with infusion reactions or loss of efficacy especially if they are of African origin. Immunized patients might be treated efficiently and safely with ofatumumab. This alternative should be further evaluated for sAID., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: Competing interests: RS received consulting fees from Roche (<10.000€). Other authors declared any competing interest in link with the present study.

Objective: The usefulness of positron emission tomography-computed tomography (PET-CT) with 18 F-labeled fluorodeoxyglucose ( 18 F-FDG) for the diagnosis of lymphoma in patients with primary Sjögren's syndrome (SS) is unclear, since the abnormalities it reveals may be due to systemic manifestations of SS. This study was undertaken to compare 18 F-FDG-PET-CT in patients with primary SS with lymphoma and those without lymphoma in order to identify patterns associated with lymphoma., Methods: A retrospective study was conducted in 2 centers and included patients who met the American College of Rheumatology/European League Against Rheumatism 2016 criteria for primary SS and had undergone PET-CT. Two independent readers who were blinded with regard to lymphoma diagnosis analyzed PET-CT scans. Abnormalities were compared between patients with and those without lymphoma., Results: Of the 45 patients included, 15 had lymphoma. Compared to patients without lymphoma, the mean size (P = 0.048) and maximum standardized uptake value (SUVmax) (P = 0.001) of the parotid glands were higher in patients with lymphoma. FDG uptake in the lymph nodes was observed in 53.3% of the patients with lymphoma and 43.3% of the patients without lymphoma, with no difference in the number of sites, uptake pattern, or mean SUVmax. Focal pulmonary uptake (nodules or condensations) was observed in 5 of the patients with lymphoma (33.3%) but only 1 patient without lymphoma (3.3%) (P = 0.01). Having an SUVmax in the parotid gland of ≥4.7 and/or the presence of focal pulmonary lesions was highly suggestive of lymphoma (sensitivity 80%, specificity 83.3%)., Conclusion: Some systemic manifestations of primary SS (lymphadenopathy, pulmonary involvement, and salivary gland involvement) can be visualized by PET-CT. Involvement of the lymph nodes and parotid glands is commonly observed with a similar frequency in SS patients with and those without lymphoma. An SUVmax in the parotid glands of ≥4.7 and/or the presence of focal lung lesions are associated with the diagnosis of lymphoma., (© 2019, American College of Rheumatology.)

Objective: To investigate maintenance of rituximab (RTX) in RA patients re-treated with reduced doses compared with standard dose in a real life setting., Methods: The Autoimmunity and Rituximab (AIR) registry is a nationwide prospective observational cohort investigating the long-term safety and efficacy of RTX in RA. The present study included patients from the AIR registry that have been re-treated with RTX after a first course of RTX standard dose (1000 mg × 2). Two groups were defined according to dose of RTX of the first retreatment course (i.e. second course): standard dose group and reduced dose group. Five years' maintenance and rate of serious infections of the retreatment period were compared between standard dose and reduced dose groups. Analyses used the inverse probability of treatment weighting propensity score adjusted method., Results: Among the 1986 patients from the AIR registry, 1278 were included, 1093 (85.5%) treated with standard dose and 185 (14.5%) with reduced doses. Maintenance of RTX at 5 years in the standard and reduced groups was 55.5 and 53.8%, respectively, and did not significantly differ between groups in adjusted analyses (hazard ratio = 1.03; 95% CI: 0.81, 1.30), but the cumulative RTX dose received for retreatment [1.4 (0.6) vs 2.3 (1.0) g/year, P < 0.001] and the rate of serious infections were significantly lower in the reduced dose group (adjusted hazard ratio = 0.50; 95% CI: 0.27, 0.92; P = 0.02)., Conclusion: Use of reduced doses of RTX for retreatment did not alter the maintenance of RTX at 5 years in RA patients, but allowed a 39% total dose reduction and a lower rate of serious infections., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Prior research using functional magnetic resonance imaging (fMRI) [1-4] and behavioral studies of patients with acquired or congenital amusia [5-8] suggest that the right posterior superior temporal gyrus (STG) in the human brain is specialized for aspects of music processing (for review, see [9-12]). Intracranial electrical brain stimulation in awake neurosurgery patients is a powerful means to determine the computations supported by specific brain regions and networks [13-21] because it provides reversible causal evidence with high spatial resolution (for review, see [22, 23]). Prior intracranial stimulation or cortical cooling studies have investigated musical abilities related to reading music scores [13, 14] and singing familiar songs [24, 25]. However, individuals with amusia (congenitally, or from a brain injury) have difficulty humming melodies but can be spared for singing familiar songs with familiar lyrics [26]. Here we report a detailed study of a musician with a low-grade tumor in the right temporal lobe. Functional MRI was used pre-operatively to localize music processing to the right STG, and the patient subsequently underwent awake intraoperative mapping using direct electrical stimulation during a melody repetition task. Stimulation of the right STG induced "music arrest" and errors in pitch but did not affect language processing. These findings provide causal evidence for the functional segregation of music and language processing in the human brain and confirm a specific role of the right STG in melody processing. VIDEO ABSTRACT., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We present a rare case of a large infarcted submucous fibroid removed manually after a normal vaginal delivery. This patient was known to have a large postero-fundal hybrid predominantly intramural uterine fibroid, measuring 11 x 10 cm in diameter and diagnosed 2 years prior to last conception. Thirty-five days postpartum, she presented with severe lower abdominal pain and foul smell per vaginum. Abdominal examination revealed a very tender bulky uterus at 24 weeks size, and vaginal examination revealed a big fleshy smelly mass with friable surface just bulging from a dilated cervix. Examination under anaesthesia revealed a very foul smelly large pedunculated submucous fibroid that was felt through a dilated cervix. It was deliverable vaginally, so the submucous leiomyoma was removed manually, a procedure similar to manual removal of placenta. Histopathology examination confirmed an infarcted massive fibroid., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To assess the link between monoclonal gammopathy (MG), disease activity, and incidence of malignant hematologic disorders (MHDs), including lymphoma and multiple myeloma (MM), in patients with primary Sjögren's syndrome (SS)., Methods: Screening for the presence of MG was performed in 352 primary SS patients. Each patient with MG was paired with 2 age- and sex-matched primary SS controls without MG. Their characteristics were compared for the presence of risk factors for MG and for the relationship between MG and MHD., Results: Twenty-six of the 352 primary SS patients (7.4%) had MG; 88% were women, with a median age of 62.7 years (interquartile range [IQR] 50.3-69.1 years) and a median disease duration of 7.8 years (IQR 3.6-12.8 years). The parameters associated with MG on multivariate analysis were higher disease activity, as measured by either the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI; adjusted odds ratio [OR] 9.7, P = 0.0002) or the Clinical ESSDAI (adjusted OR 6.7, P = 0.001), and low C4 level (adjusted OR 3.4, P = 0.04). After a median follow-up of 6.3 years (IQR 3.1-9.5 years), 10 patients with MG had developed an MHD (38.5%; 4 had lymphomas and 6 had MM), as compared with 4 patients in the control group (7.7%; all had lymphomas) (OR 7.5, P = 0.002). The only factor associated with the risk of MHDs was the presence of MG (adjusted OR 5.5, P = 0.02), which was principally associated with an increased risk of MM (23% versus 0%; P = 0.0009), but not lymphoma (15% versus 8%; P = 0.3)., Conclusion: The presence of MG was associated with higher disease activity and an increased risk of MHD in primary SS. In the presence of MG, the risk of MM was even higher than the risk of lymphoma. These results suggest that regular monitoring of primary SS patients with MG for the emergence of both lymphoma and MM is necessary., (© 2016, American College of Rheumatology.)

Monoclonal antibodies targeted against the immune checkpoint molecules CTLA-4 and PD-1 have recently obtained approval for the treatment of metastatic melanoma and advanced/refractory non small-cell lung cancers. Therefore, their use will not be limited anymore to selected hospitals involved in clinical trials. Indeed, they will be routinely prescribed in many cancer centers across the world. Besides their efficacy profile, these immune targeted agents also generate immune-related adverse events (irAEs). This new family of dysimmune toxicities remains largely unknown to the broad oncology community. Although severe irAEs remain rare (∼10% of cases under monotherapy), they can become life-threatening if not anticipated and managed appropriately. Over the last 5 years, Gustave Roussy has accumulated a significant experience in the prescription of immune checkpoint blockade (ICB) antibodies and the management of their toxicities. Together with the collaboration of Gustave Roussy's network of organ specialists with expertise in irAEs, we propose here some practical guidelines for the oncologist to help in the clinical care of patients under ICB immunotherapy., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Non-Hodgkin's lymphoma (NHL) is a severe complication of primary Sjögren's syndrome (SS). Ectopic germinal centers (GCs) in the salivary glands are predictors of the occurrence of NHL. Given the association between CCL11 and CXCL13 and ectopic GCs, we assessed the link between these chemokines and NHL, as well as the association between these chemokines and disease activity, in patients with primary SS., Methods: Serum levels of CCL11 and CXCL13 were evaluated by multiplex assay in 385 patients included in the Assessment of Systemic Signs and Evolution of Sjögren's Syndrome (ASSESS) cohort. The association between chemokine levels, B cell biomarkers, and patient subsets was assessed using Spearman's test for continuous data and the nonparametric Mann-Whitney U test for categorical data. Multivariate analyses were performed to identify parameters associated with lymphoma and disease activity., Results: Seventeen patients had a history of lymphoma, and 5 of them had developed NHL during followup. The median serum levels of CCL11 and CXCL13 in the total cohort were 106.48 pg/ml (interquartile range 69.33-149.85) and 108.31 pg/ml (interquartile range 58.88-200.13), respectively. Patients with lymphoma had higher levels of CXCL13 than did patients without lymphoma (P = 0.006) and a trend toward a higher level of CCL11 (P = 0.056). Low C4 and high BAFF levels were associated with NHL on multivariate analysis (P = 0.01 and P = 0.0002, respectively). CCL11 and CXCL13 levels correlated positively with the rheumatoid factor titer, the κ-to-λ free light chain ratio, and the β2 -microglubulin level. CXCL13 was the only parameter associated with disease activity on multivariate analysis., Conclusion: These findings demonstrate a link between CXCL13 and CCL11 and disease activity and lymphoma. This highlights the continuum between chronic B cell activation, disease activity, and lymphomagenesis in patients with primary SS., (© 2015, American College of Rheumatology.)

Introduction: In this study, we sought to address changes in blood lymphocyte subpopulations and labial salivary gland (LSG) inflammation after belimumab treatment in patients with primary Sjögren's syndrome (pSS) and to identify predictors of response to treatment., Methods: Sequential blood lymphocyte subsets and LSG biopsies were analysed between week 0 (W0) and W28 in 15 patients with pSS treated with belimumab. Systemic response to treatment was defined as a decrease in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index score of ≥3 points at W28., Results: After belimumab, we observed a decrease in blood B lymphocytes primarily involving CD27-negative/immunoglobulin D-positive naïve B cells (p=0.008). Lymphocytic sialadenitis (focus score >1) that was present in 12 patients (80.0 %) before belimumab treatment became negative in 5 of them after treatment (p=0.03). The median (interquartile range) LSG B-cell/T-cell ratio decreased from 0.58 (0.5-0.67) to 0.50 (0.5-0.5) (p=0.06). B-cell activating factor (BAFF) staining was detected in 11 (78.6 %) of 14 patients before belimumab treatment compared with 7 (50.0 %) of 14 after belimumab therapy (p=0.10). The median percentage of BAFF-positive cells in foci significantly decreased from 27.5 % (10-40) to 5 % (0-20) (p=0.03). A systemic response was achieved in six patients (40 %). The only predictor of response was the presence of a low number of natural killer (NK) cells, both in blood (8.5 % [7-10] vs 11 % [9-21]; p=0.04) and in LSG (20.6/mm(3) [20.0-21.4] vs 30.0/mm(3) [25.0-100.0], p=0.003). Serum BAFF levels did not influence response to treatment., Conclusions: Low blood and salivary NK cell numbers are associated with a better response to belimumab. This suggests that two distinct subsets of pSS may exist: one with a predominant type I interferon (IFN)-BAFF-B-cell axis, representing good responders to belimumab; and one with a predominant type II IFN-NK cell axis, representing non-responders., Trial Registration: ClinicalTrials.gov identifier: NCT01160666 . Registered 9 July 2010.

Objectives: Anticyclic citrullinated protein antibodies (ACPA) are highly specific of rheumatoid arthritis (RA). However, they have also been detected in 5-10% of primary Sjögren's syndrome (pSS). We compared ACPA-positive and negative patients with pSS and assessed the risk of evolution to RA., Patients and Methods: ACPA-positive and negative patients with pSS were included in this study. For ACPA-positive patients, clinical and radiological re-evaluation was systematically performed after at least 5 years of follow-up. Diagnosis was reassessed at the end of the follow-up to identify patients that developed RA according to the American College of Rheumatology 1987 classification criteria., Results: At inclusion in the cohort 16 patients with pSS were ACPA positive and 278 were ACPA negative. ACPA-positive patients, had more frequently arthritis (43.7% vs 12.2%; p=0.003) but not arthralgias. They also had more frequent lung involvement (25% vs 8.1%; p=0.05). After median follow-up of 8 (5-10) years, 7/16 (43.8%) patients developed RA including 5 (31.25%) with typical RA erosions. Elevation of acute phase reactants at inclusion was the only parameter associated with progression to erosive RA., Conclusions: Median term follow-up of ACPA-positive patients with pSS showed that almost half of them developed RA, particularly in the presence of elevation of acute phase reactants. These results support the usefulness of a close radiological monitoring of these patients for early detection of erosive change not to delay initiation of effective treatment. Indeed, number of these patients with ACPA-positive pSS may actually have RA and associated SS.