Background and ObjectivesTo evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti–interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein–IgG–associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD).MethodsAnnualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab.ResultsPatients received TCZ for 23.8 months (median; interquartile range 13.0–51.1 months), with an IV dose of 8.0 mg/kg (median; range 6–12 mg/kg) every 31.6 days (mean; range 26–44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5–5) to 0 (range 0–0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0–5] to 0 [range 0–4.2]; p < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0–3.0] to 0.2 [range 0–2.0]; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD (p = 0.04; for the brain) and in AQP4-IgG+ NMOSD (p < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy.DiscussionThis study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD.

Ageing of the human organism results in the accumulation of modified molecules. Some of these molecular changes may be used for age estimation, as already shown for aspartic acid racemization (AAR). Another example for an accumulation of damaged molecules is advanced glycation end products (AGEs). We examined, (1) if the correlation between the concentration of AGEs (pentosidine) in root dentine and age is close enough to be used as basis for age estimation, and (2) if the combined analysis of AGEs and AAR in dentine may be a useful approach to rule out or to detect relevant effects of confounding factors in age estimation. We determined the pentosidine content of root dentine samples of 64 healthy teeth as well as in carious, "pink", diabetic and heated teeth, and in teeth after different storage times. In 23 teeth, the extent of aspartic acid racemization (AAR) was determined in parallel. We observed a close relationship between the concentration of pentosidine in dentine and chronological age (r = 0.94) in healthy teeth. The analysis of pentosidine in dentine can theoretically be used as a basis for age estimation in healthy teeth of non-diabetic individuals; diabetic individuals may exhibit very high pentosidine levels in dentine. This finding limits the application of this method, since information regarding the question if an unidentified person suffered from diabetes mellitus or not are missing in most cases. Moreover, the method is not suitable to identify or rule out the influence of confounding factors in age estimation based on AAR, since both methods are sensible to the most relevant confounding factors (caries, heat).

Dental neglect may have serious consequences for children's health. Moreover, it may indicate general negligence and it can be associated with child abuse. Therefore, a highly professional case management is of utmost importance, but also poses a great challenge for dentists. In order to develop effective strategies for an optimization of dental care in cases of dental neglect, a better understanding of the situation, and in particular an investigation into the unsolved questions of dentists in these cases, is needed. A prospective clinical examination with ten dentists was carried out to identify their challenges in the treatment of and the care for children facing suspicion of dental neglect. The practice of dental care in the cases of 102 children with suspicion of dental neglect (ages 3-14 years) was analyzed by collecting quantitative data (questionnaires) as well as qualitative data (focus group interviews). Severe and complex challenges in the handling of dental neglect in dental practice were identified. The study revealed that steps towards an optimization of the care for children with suspicion on dental neglect, which is much more than the treatment of caries, are needed. As such steps, we propose (1) the drafting of precise guidelines, (2) the education and training of dental students and dentists in general, (3) mandatory periodical dental health screenings, (4) the establishment of an interdisciplinary cooperation within the public health system, (5) the education of families, and (6) an adequate financial compensation for a professional and optimized case management. The establishment of efficient strategies of prevention and treatment of dental neglect and associated risks for the health of affected children will only be achieved with intense public and governmental support.

This manuscript presents practical recommendations for managing acute attacks and implementing preventive immunotherapies for neuromyelitis optica spectrum disorders (NMOSD), a rare autoimmune disease that causes severe inflammation in the central nervous system (CNS), primarily affecting the optic nerves, spinal cord, and brainstem. The pillars of NMOSD therapy are attack treatment and attack prevention to minimize the accrual of neurological disability. Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) are a diagnostic marker of the disease and play a significant role in its pathogenicity. Recent advances in understanding NMOSD have led to the development of new therapies and the completion of randomized controlled trials. Four preventive immunotherapies have now been approved for AQP4-IgG-positive NMOSD in many regions of the world: eculizumab, ravulizumab - most recently-, inebilizumab, and satralizumab. These new drugs may potentially substitute rituximab and classical immunosuppressive therapies, which were as yet the mainstay of treatment for both, AQP4-IgG-positive and -negative NMOSD. Here, the Neuromyelitis Optica Study Group (NEMOS) provides an overview of the current state of knowledge on NMOSD treatments and offers statements and practical recommendations on the therapy management and use of all available immunotherapies for this disease. Unmet needs and AQP4-IgG-negative NMOSD are also discussed. The recommendations were developed using a Delphi-based consensus method among the core author group and at expert discussions at NEMOS meetings.

This current study investigated which angle of canine inclination (angle between canine tooth axis (CA-line) and the line between the lateral canthus and the ipsilateral labial angle (EM-line)) is perceived to be most attractive in a smile. The second objective was to determine whether laymen and dental experts share the same opinion. A Q-sort assessment was performed with 48 posed smile photographs to obtain two models of neutral facial attractiveness. Two sets of images (1 male model set, 1 female model set), each containing seven images with incrementally altered canine and posterior teeth inclinations, were generated. The images were ranked for attractiveness by three groups (61 laymen, 59 orthodontists, 60 dentists). The images with 0° inclination, that is CA-line (maxillary canine axis) parallel to EM-line (the line formed by the lateral canthus and the ipsilateral corner of the mouth) (male model set: 54·4%; female model set: 38·9%), or -5° (inward) inclination (male model set: 20%; female model set: 29·4%) were perceived to be most attractive within each set. Images showing inward canine inclinations were regarded to be more attractive than those with outward inclinations. Dental experts and laymen were in accordance with the aesthetics. Smiles were perceived to be most attractive when the upper canine tooth axis was parallel to the EM-line. In reconstructive or orthodontic therapy, it is thus important to incline canines more inwardly than outwardly.