Pain in Multiple System Atrophy a Systematic Review and Meta-Analysis

Background: Individuals with multiple system atrophy (MSA) often complain about pain, nonetheless this remains a poorly investigated non-motor feature of MSA. Objectives: Here, we aimed at assessing the prevalence, characteristics, and risk factors for pain in individuals with MSA. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, we systematically screened the PubMED, Cochrane, and Web of Science databases for papers published in English until September 30, 2022, combining the following keywords: “pain,” “multiple system atrophy,” “MSA,” “olivopontocerebellar atrophy,” “OPCA,” “striatonigral degeneration,” “SND,” “Shy Drager,” and “atypical parkinsonism.”. Results: The search identified 700 records. Sixteen studies provided information on pain prevalence in cohorts of MSA individuals and were included in a qualitative assessment based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Thirteen studies (11 cross-sectional, two longitudinal) scored ≥14 points on QUADAS assessment and were included in a quantitative analysis, pooling data from 1236 MSA individuals. The resulting pooled prevalence of pain in MSA was 67% (95% confidence intervals [CI] = 57%–75%), and significantly higher in individuals with MSA of parkinsonian rather than cerebellar type (76% [95% CI = 63%–87%] vs. 45% [95% CI = 33%–57%], P = 0.001). Pain assessment tools and collected information were highly heterogeneous across studies. Two studies reported pain treatment strategies and found that only every second person with MSA complaining about pain had received targeted treatment. Conclusions: We found that pain is a frequent, but still under-recognized and undertreated feature of MSA. Further research is needed to improve pain detection and treatment in MSA

Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy.

In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene. The co-occurrence of predicted deleterious SRPK3/TTN variants was not seen among 76,702 healthy male individuals, and statistical modeling strongly supported digenic inheritance as the best-fitting model. Furthermore, double-mutant zebrafish (srpk3-/-; ttn.1+/-) replicated the myopathic phenotype and showed myofibrillar disorganization. Transcriptome data suggest that the interaction of srpk3 and ttn.1 in zebrafish occurs at a post-transcriptional level. We propose that digenic inheritance of deleterious changes impacting both the protein kinase SRPK3 and the giant muscle protein titin causes a skeletal myopathy and might serve as a model for other genetic diseases

Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy

\ua9 The Author(s) 2024.In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene. The co-occurrence of predicted deleterious SRPK3/TTN variants was not seen among 76,702 healthy male individuals, and statistical modeling strongly supported digenic inheritance as the best-fitting model. Furthermore, double-mutant zebrafish (srpk3−/−; ttn.1+/−) replicated the myopathic phenotype and showed myofibrillar disorganization. Transcriptome data suggest that the interaction of srpk3 and ttn.1 in zebrafish occurs at a post-transcriptional level. We propose that digenic inheritance of deleterious changes impacting both the protein kinase SRPK3 and the giant muscle protein titin causes a skeletal myopathy and might serve as a model for other genetic diseases

2016 ACR-EULAR adult dermatomyositis and polymyositis and juvenile dermatomyositis response criteria-methodological aspects

Objective. The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM. Methods. Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data. Results. Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference. Conclusion. Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis

Algae‐derived hydroxyapatite behavior as bone biomaterial in comparison with anorganic bovine bone: A split‐mouth clinical, radiological, and histologic randomized study in humans

This is the peer reviewed version of the following article: [Galindo-Moreno P, Padial-Molina M, Lopez-Chaichio L, Gutiérrez-Garrido L, Martín-Morales N, O'Valle F. Algae-derived hydroxyapatite behavior as bone biomaterial in comparison with anorganic bovine bone: A split-mouth clinical, radiological, and histologic randomized study in humans. Clin Oral Implants Res. 2020 Jun;31(6):536-548. doi: 10.1111/clr.13590. Epub 2020 Mar 6], which has been published in final form at [https://doi.org/10.1111/clr.13590]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.Objectives: To analyze a modified biphasic phycogenic biomaterial in comparison with anorganic bovine bone in maxillary sinus floor elevation in humans. Material and methods: Eight male patients in need of bilateral two-stage sinus floor elevation were consecutively recruited for this randomized split-mouth study. A combination of autogenous cortical bone (ACB, 20%) and anorganic bovine bone (ABB, 80%) (ACB + ABB group) or ACB (20%) and modified biphasic phycogenic material (BP, 80%) (ACB + BP group) were randomly assigned to graft each sinus. Patients were followed up for 6 months post-surgery when bone samples were collected for analysis. Results: Radiographically, bone height gain was statistically higher in the ACB + ABB versus the ACB + BP group. While the analysis of the biological compartments showed differences in non-mineralized tissue (39.15 ± 20.97% vs. 65.87 ± 28.59%, ACB + ABB vs. ACB + BP respectively; p = .018) and remnant biomaterial particles (22.62 ± 17.01% vs. 7.96 ± 8.57%, respectively; p = .028), the percentage of mineralized tissue (38.23 ± 17.55% vs. 24.14 ± 24.66%, respectively; p = .398) showed no statistically significant difference. In contrast, ACB + ABB biopsies showed higher Musashi-1-positive cells per mm2 compared to ACB + BP biopsies (811.49 ± 875.30 vs. 236.90 ± 280.81; p < .018), where the fusiform cells corresponded mainly with fibroblasts, as demonstrated by ultrastructural analysis. Conclusion: Both combinations of materials exhibited bone formation after 6 months of healing in the maxillary sinus cavity. However, the combination with biphasic phycogenic biomaterial induced a higher radiographical vertical resorption and graft collapse in comparison with the combination with anorganic bovine bone, possibly due to a higher remodeling of the graft.Junta de Andalucía #CTS-138 and #CTS-102

A 2-year prospective case series on volumetric changes, PROMs, and clinical outcomes following sinus floor elevation using deproteinized bovine bone mineral as filling material

Background A sinus floor augmentation may be indicated when a lack of hard tissue impedes implant placement. Although clinically successful, evidence supporting the long-term three-dimensional stability of the grafted volume is scarce. Second, evidence on the patient's acceptance of this type of treatment is limited. Purpose First is to evaluate the changes in graft volume after lateral wall sinus lifting based on superimposed cone beam computed tomography (CBCT) images and then to assess patient-reported outcome measures (PROMs) and clinical outcomes. Materials and Methods Partially edentulous patients in need of a sinus lift and fixed reconstruction on at least two neighboring implants were selected for a prospective case series. Lateral wall sinus augmentation was performed using deproteinized bovine bone mineral (DBBM) as the only filling material. Volumetric changes were quantified on the basis of a preoperative CBCT and three postoperative CBCTs (at 2 weeks, 3 months, and 2 years). PROMs and clinical parameters were registered. Results Twenty-two patients (7 males, 15 females; mean age 59 years) participated of which three patients dropped out during the follow up. Graft volumes amounted to 1418.26 mm(3) at 2 weeks, 1201.21 mm(3) at 3 months, and 1130.13 mm(3) at 2 years postoperative pointing to a relative graft volume stability of 79.7%. Swelling was the leading symptom during the first week. A peak in visual analogue scale scores was observed for pain, swelling, and hematoma the day of surgery and 1 day postoperation with a statistically significant decline between days 3 and 7. Hemorrhage and nose bleeding occurred in 18.2% and 27.3% of the subjects, respectively. About 95.5% of the subjects would undergo the treatment again. All implants integrated successfully and demonstrated healthy clinical conditions. Conclusion Lateral wall sinus augmentation using DBBM as the only filling material is a viable treatment concept given limited graft resorption, good patients' tolerance, and clinical outcomes