Inflammatory myopathies with anti-Ku antibodies: a prognosis dependent on associated lung disease

Anti-Ku antibodies have been reported in a wide spectrum of autoimmune diseases, sometimes in association with inflammatory myopathies (IM). We studied the clinical, laboratory, and muscle histologic features of all anti-Ku-positive patients detected in our hospital during the last 10 years, as well as their treatment and outcomes. Anti-Ku antibodies were found in 34 patients (0.46% of 20,600 sera positive for antinuclear antibodies), and complete data were available for 30 patients; 86.7% were female, mean age was 49 years (range, 20-73 yr). The most frequent clinical manifestations were arthralgia (77%) and Raynaud phenomenon (53%). Eleven (37%) patients had IM, 8 of them as part of an overlap syndrome defined as IM associated with connective autoimmune disease (5 systemic sclerosis [SSc], 2 Sj?gren syndrome (SS), and 1 systemic lupus erythematosus [SLE]). Of 21 patients without IM, 19 had autoimmune diseases (including 6 SLE, 2 SSc, 2 SS, and 2 rheumatoid arthritis), 1 had bronchial neoplasia, and 1 had nephroangiosclerosis. Clinical features of the 9 patients with IM were myalgia (91%), proximal muscle weakness (89%), and dysphagia (36%). All had increased creatine kinase (median, 2210 U/L; range, 194-4073 U/L). Muscle biopsy showed necrosis, inflammation, and positive HLA class I immunostaining. Interstitial lung disease (ILD) was detected on computed tomography (CT) scan in 11 patients (37%) and was significantly more frequent in patients with IM (82% vs. 10.5%, p < 0.001). Fourteen (47%) patients required no immunosuppressive treatment or only a low corticosteroid dose (<15 mg/d, n = 3). A high dose of corticosteroids was more frequently administered in patients with IM (10/11 cases, 80% with associated ILD) than in patients without IM (4/19 cases, 0 with ILD). Complete muscle remission after steroids occurred in 73% of patients with IM. Lung disease was corticoresistant in 6 of 8 (75%) treated cases.Anti-Ku antibodies remain rarely detected, but their presence can be frequently associated with corticosensitive IM and severe, corticoresistant ILD.     

Back pain prevention program: An evaluation after a 10-year implementation amongst dental students

Background

Many studies show a higher prevalence of back pain for dentists and dental students than in the general population. This leads to a need to integrate an effective back pain prevention program (BPPP) into the student's curriculum. We have implemented such a program for 10 years, and the objective was to evaluate its effectiveness.

Material and Methods

Data from 102 dentists and students who benefited from the BPPP were collected. Back pain prevalence and its intensity (0–10 scale) regarding neck, upper back and lower back location were studied, as well as sex, age, implementation or not of elements of the BPPP into daily practice, and if so at what moment of the professional life. For identical items, answers were compared with those from a national survey conducted amongst French students and practitioners in 2018.

Results

Amongst the BPPP beneficiaries, 60% were suffering from chronic back pain versus 77% in the previous national survey (p < .001). Mean pain intensity was lower in each location for the BPPP beneficiaries on the 0–10 scale: neck 1.91 vs. 2.40 (p = .05); upper back 1.94 vs. 2.72 (p < .001); lower back 2.26 vs. 2.67 (p = .15). Respondents who implemented elements of the BPPP from the start of their clinical practice showed a prevalence of chronic back pain of 48.4%, against 77% for respondents who did so only from the first year or after (p < .05).

Conclusion

Our BPPP seems to show a positive preventive effect on dentists and students after a 10-year implementation. It is a solid basis that can however be further improved.     

Efficacy of a short sandwich protocol,methotrexate, gemcitabine,L-asparaginase and dexamethasone chemotherapy combined with radiotherapy,in localised newly diagnosed NK/T-cell lymphoma: A French retrospective study

Extranodal NK/T-cell lymphoma, nasal type is a rare and aggressive form of lymphoma, historically associated with poor prognosis. We report here the results of a retrospective multi-centre study evaluating the efficacy of MGAD (methotrexate, gemcitabine, L-asparaginase and dexamethasone) regimen (two cycles) combined with ‘sandwich’ radiotherapy in 35 patients with localised newly diagnosed extranodal NK/T-cell lymphoma. Thirty-two patients (91%) reached complete remission. With a long median follow-up of 59.6 months, progression-free and overall survival at 2 and 5 years were 71%, 80% and 53%, 73%, respectively. Around one third of the patients experienced relapse within a median time of 14.5 months. Side-effects were manageable with grades 3–4 cytopenias, mucositis and infection in 50%, 24% and 21% of the cases, respectively. Monitoring of asparaginase activity was performed in 13 patients and showed inactivation of the drug in seven (54%) patients. Our results indicate that a short therapy by sandwich MGAD chemoradiotherapy is a tolerable and effective treatment option in localised newly diagnosed extranodal NK/T-cell lymphoma patients.     

Weak antibody response to three doses of mRNA vaccine in kidney transplant recipients treated with belatacept

Poor responses to mRNA COVID-19 vaccine have been reported after 2 vaccine injections in kidney transplant recipients (KTRs) treated with belatacept. We analyzed the humoral response in belatacept-treated KTRs without a history of SARS-CoV-2 infection who received three injections of BNT162b2-mRNA COVID-19 vaccine. We also investigated vaccine immunogenicity in belatacept-treated KTRs with prior COVID-19 and characterized symptomatic COVID-19 infections after the vaccine in belatacept-treated KTRs. Among the 62 belatacept-treated KTRs (36 [58%] males), the median age (63.5 years IQR [51–72]), without COVID-19 history, only four patients (6.4%) developed anti-SARS-CoV-2 IgG with low antibody titers (median 209, IQR [20–409] AU/ml). 71% were treated with mycophenolic acid and 100% with steroids in association with belatacept. In contrast, in all the 5 KTRs with prior COVID-19 history, mRNA vaccine induced a strong antibody response with high antibody titers (median 10 769 AU/ml, IQR [6410–20 069]) after two injections. Seroprevalence after three-vaccine doses in 35 non-belatacept-treated KTRs was 37.1%. Twelve KTRs developed symptomatic COVID-19 after vaccination, including severe forms (50% of mortality). Breakthrough COVID-19 occurred in 5% of fully vaccinated patients. Administration of a third dose of BNT162b2 mRNA COVID-19 vaccine did not improve immunogenicity in KTRs treated with belatacept without prior COVID-19. Other strategies aiming to improve patient protection are needed.     

Dietary fat exacerbates postprandial hypothalamic inflammation involving glial fibrillary acidic protein‐positive cells and microglia in male mice

In humans, obesity is associated with brain inflammation, glial reactivity, and immune cells infiltration. Studies in rodents have shown that glial reactivity occurs within 24 hr of high‐fat diet (HFD) consumption, long before obesity development, and takes place mainly in the hypothalamus (HT), a crucial brain structure for controlling body weight. Here, we sought to characterize the postprandial HT inflammatory response to 1, 3, and 6 hr of exposure to either a standard diet (SD) or HFD. HFD exposure increased gene expression of astrocyte and microglial markers (glial fibrillary acidic protein [GFAP] and Iba1, respectively) compared to SD‐treated mice and induced morphological modifications of microglial cells in HT. This remodeling was associated with higher expression of inflammatory genes and differential regulation of hypothalamic neuropeptides involved in energy balance regulation. DREADD and PLX5622 technologies, used to modulate GFAP‐positive or microglial cells activity, respectively, showed that both glial cell types are involved in hypothalamic postprandial inflammation, with their own specific kinetics and reactiveness to ingested foods. Thus, recurrent exacerbated postprandial inflammation in the brain might promote obesity and needs to be characterized to address this worldwide crisis.