Hasil untuk "Diseases of the musculoskeletal system"

Guanglei Zhao, Yue Shen, Jingchun Ma et al.

Background: Osteoarthritis (OA), a debilitating joint disorder lacking disease-modifying therapies, involves ferroptosis-an iron-dependent cell death. While ferroptosis contributes to OA progression, its autophagy-dependent mechanisms remain undefined. This study reveals DMT1 (divalent metal transporter 1) as a central regulator of autophagic ferroptosis in OA pathogenesis. Methods: OA-related ferroptosis genes were screened by LASSO regression and random forest models. IL-1β/Erastin-stimulated chondrocytes and DMM-induced OA mice were used to investigate DMT1 function. Ferroptosis and autophagy were assessed by lipid peroxidation, autophagic flux, Western blot, and modulators. Micro-CT, OARSI scoring and behavioral tests evaluated joint damage. Regulatory mechanisms were examined by miR-17-5p mimic, luciferase assays and NEDD4-mediated ubiquitination. Results: DMT1 was upregulated in OA cartilage and IL-1β-stimulated chondrocytes, correlating with ferroptosis activation. Genetic DMT1 suppression attenuated ferroptosis in vitro and in vivo, whereas overexpression exacerbated lipid peroxidation and impaired cartilage repair post-DMM surgery in mice. Mechanistically, DMT1 overexpression activated autophagy, linking it to ferroptosis execution – pharmacological autophagy inhibition reduced DMT1-driven ferroptosis, while autophagy inducers amplified its effects. Conclusions: We identified a DMT1–autophagy–ferroptosis axis as a critical OA mechanism. Ferroptosis inhibitors and upstream regulators (miR-17-5p, NEDD4) show promise as disease-modifying strategies for OA. The translational potential of this article: This study not only elucidates a novel DMT1-autophagy-ferroptosis axis but also identifies NEDD4 as upstream therapeutic targets. The demonstration that Lip-1 treatment alleviates DMT1-driven OA exacerbation in vivo highlights translational potential of ferroptosis inhibition as a disease-modifying strategy for OA. Moreover, NEDD4 overexpression represents promising gene-based interventions with potential for precision therapy in OA.

Società Italiana di Reumatologia

Background. To investigate clinical and ultrasound (US) findings as potential predictors of difficult-to-treat rheumatoid arthritis (D2TRA).1,2   Methods. Patients diagnosed with D2TRA assessed at our clinic between 2020 and 2024 were enrolled in the study and compared with a group of consecutive non-D2TRA patients. Demographic, US and clinical data were retrospectively collected. The first US available before developing D2TRA was analyzed. All US assessments were performed by four expert rheumatologists from our center using an Esaote MyLabX8 US machine equipped with a high-frequency (15–24 MHz) linear probe. US evaluation included the detection of synovitis, tenosynovitis and bone erosions. Assessed joints encompassed wrists, metacarpophalangeal (MCP), proximal interphalangeal (PIP), shoulders, knees and ankles. Regarding synovitis, GS and PD were considered in accordance with EULAR and OMERACT criteria.3,4,5 GLOESS grading system was also applied.6 Logistic and Cox regression models adjusted for baseline confounders was used for multivariable analysis.   Results. One hundred thirty-six patients were recruited, median (±IQR) follow-up 18.75 (11.42-25.92) years, 80 of them fulfilling EULAR criteria for D2TRA. No significant differences were found between D2TRA and non-D2TRA groups regarding baseline demographics and comorbidities except for fibromyalgia, which was significantly more frequent in D2T cohort (Table 1). On survival univariate analysis, exposure to tsDMARDs was associated to longer time-to-D2T development (HR [CI] : 0.51, [0.26 - 0.99], p=0.046) (Figure 1). 136 US were included in the study. At the time of US examination, patients further-to-be D2T displayed higher DAS28 scores (median [IQR]: 4.30 [3.67-5.40] vs 2.70 [2.02-4.41], p<0.01). A significantly higher prevalence of wrist synovitis (n [%]: 62 [77.5%] vs. 31 [57.4%], p=0.023) and higher wrist GLOESS scores (mean [sd]: 2.67 [1.91] vs 1.77 [1.94]; p=0.007) were observed in furhter-to-be D2T patients (Figure 2). At the multivariable logistic analysis, wrist synovitis (OR 2.79, 95%CI 1.27-6.33, p=0.01) and fybromialgia (OR 4.14, 95%CI 1.22-19.3, p=0.03) independently predicted D2TRA.   Conclusions. In our cohort, fybromialgia and US-documented wrist synovitis independetly predicted D2TRA. Our results highlight the critical role of targeted US beside clinical assessment for risk stratification across RA patients. REFERENCES 1. Bellis et al. The role of musculoskeletal ultrasound in difficult-to-treat RA: Insights from a systematic literature review. Autoimmun Rev. 2025 2. Nagy G et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 3. Möller I et al. The 2017 EULAR standardised procedures for ultrasound imaging in rheumatology. Ann Rheum Dis 2017. 4. Costantino et al. EULAR recommendations for the reporting of ultrasound studies in rheumatic and musculoskeletal diseases. Ann Rheum Dis 2021. 5. Bruyn et al. OMERACT Definitions for Ultrasonographic Pathologies and Elementary Lesions of Rheumatic Disorders. J. Rheumatol 2019. 6. Naredo E et al.The OMERACT ultrasound task force - status and perspectives. J Rheumatol 2011.

Alexander S. Wang, Alexander S. Wang, Ibrahim M. Alkhodair et al.

Dystonia is a neurologic disorder characterized by abnormal muscle contractions and postures, which is vastly heterogeneous in its etiologies and clinical manifestations. The role of the basal ganglia in the pathogenesis of dystonia is well known, however, there has been a recent surge of evidence implicating the malfunction of a wide network, including a prominent role of the cerebellum. In this review article, we explore the role of the cerebellum in generating dystonia through multiple lines of basic science and clinical evidence. Neurophysiological, radiological, and pathological findings in various dystonia syndromes implicate an important role of the cerebellum. Dystonia additionally accompanies many known ataxic cerebellar disorders such as spinocerebellar ataxia. Genetic and pharmacologic mouse models of dystonia have demonstrated various degrees of cerebellar pathophysiology. There is emerging evidence supporting cerebellar neuromodulation in the treatment of dystonia. Lastly, we describe cerebellar, cortical, and subcortical motor connections which provide a connectomic basis where the cerebellum may play either a primary or ancillary role in generating dystonia.

Domenik Popp, Arastoo Nia, Sara Silvaieh et al.

<b>Background:</b> Acromioclavicular joint (ACJ) injuries frequently result from trauma to the shoulder girdle and are particularly common among young, physically active individuals. These injuries account for approximately 9% of all traumatic shoulder girdle injuries and often lead to functional impairment and pain. The TightRope^® system, LARS™ band, and Bosworth screw are among over 160 currently described surgical techniques for managing ACJ dislocations. However, there is no consensus regarding the optimal surgical approach, particularly for the management of moderate Rockwood Type III ACJ dislocations. <b>Materials and Methods:</b> In this retrospective study, data from 246 patients who underwent surgery for ACJ dislocation between 2010 and 2018 at the Department of Orthopedics and Trauma Surgery, Medical University of Vienna, were analyzed. Patients were divided into four cohorts based on the surgical technique used: Bosworth screw, LARS (acute), LARS (chronic), and TightRope. Clinical and radiological outcomes were assessed pre- and postoperatively using the Visual Analog Scale (VAS), Constant, Disability of the Arm, Shoulder and Hand Score (DASH), Simple Shoulder Test (SST), University of California—Los Angeles Shoulder Score (UCLA), Short Form Health Survey (SF-36), and American Shoulder and Elbow Surgeons score (ASES), as well as radiographic analysis. Radiological measurements of the acromioclavicular (AC) and coracoclavicular (CC) joint spaces were taken on both the injured and uninjured shoulders to analyze and compare the reduction in joint gaps. <b>Results:</b> All surgical methods resulted in significant reductions in AC and CC joint gaps. The TightRope and LARS acute groups showed the greatest reductions, with minimal complication rates. Complication analysis revealed significant differences in clavicular elevation (<i>p</i> < 0.001) and CC-ligament ossification (<i>p</i> = 0.006), which were most frequent in the Bosworth group and least common in TightRope^® patients, with LARS showing intermediate values. AC joint arthrosis was uncommon in all four groups and did not differ significantly (<i>p</i> = 0.13). Overall, TightRope^® was associated with the most favorable complication profile. The postoperative VAS score in the TightRope group was 1.52 ± 2.06, and the Constant score was 96.83 ± 5.41, reflecting high patient satisfaction. <b>Conclusions:</b> All systems led to satisfactory radiological and clinical outcomes, with the LARS™ band showing particular effectiveness in chronic ACJ dislocations. While all techniques provided good results, the TightRope^® system demonstrated the most favorable overall profile in our cohort and may therefore be considered a promising contemporary option. Further studies are needed to determine the optimal treatment for moderate ACJ dislocations and to assess the cost-effectiveness of these surgical techniques.

Shibo Wei, So Jeong Park, Eunah Choi et al.

ABSTRACT Background β2‐Microglobulin (B2M) has garnered considerable interest as a potential pro‐ageing factor, leading to speculation about its involvement in muscle metabolism and the development of sarcopenia, a key component of ageing phenotypes. To explore this hypothesis, we conducted a comprehensive investigation into the impact of B2M on cellular and animal muscle biology, as well as its clinical implications concerning sarcopenia parameters in older individuals. Methods In vitro myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. For in vivo research, C57BL/6 mice aged 3 months were intraperitoneally given 250 μg of B2M daily, and muscular alterations were assessed one month later. Human blood samples were obtained from 158 participants who underwent assessments of muscle mass and function at an outpatient geriatric clinic affiliated with a teaching hospital. Sarcopenia and associated parameters were assessed using cut‐off values specifically tailored for the Asian population. The concentration of serum B2M was quantified through an enzyme‐linked immunosorbent assay. Results Recombinant B2M inhibited in vitro myogenesis by increasing intracellular reactive oxygen species (ROS) production. Furthermore, B2M significantly induced differential myotube atrophy via ROS‐mediated ITGB1 downregulation, leading to impaired activation of the FAK/AKT/ERK signalling cascade and enhanced nuclear translocation of FoxO transcription factors. Animal experiments showed that mice with systemic B2M treatment exhibited significantly smaller cross‐sectional area of tibialis anterior and soleus muscle, weaker grip strength, shorter grid hanging time, and decreased latency time to fall off the rotating rod, compared to untreated controls. In a clinical study, serum B2M levels were inversely associated with grip strength, usual gait speed and short physical performance battery (SPPB) total score after adjustment for age, sex, and body mass index, whereas sarcopenia phenotype score showed a positive association. Consistently, higher serum B2M levels were associated with higher risk for weak grip strength, slow gait speed, low SPPB total score, and poor physical performance. Conclusion These results provide experimental evidence that B2M exerted detrimental effects on muscle metabolism mainly by increasing oxidative stress. Furthermore, we made an effort to translate the results of in vitro and animal research into clinical implication and found that circulating B2M could be one of blood‐based biomarkers to assess poor muscle health in older adults.

Francisco A. Ferreira, Catarina C. Santos, António L. Palmeira et al.

Background/Objectives: Swimming is a popular and cost-effective way to prevent sedentary behavior and improve physical conditioning and health during early adolescence. However, information on its impact and benefits on daily life activities is lacking. This systematic review aims to summarize the chronic effects of swimming on physical conditioning and physical health outcomes in early adolescents. Methods: The PRISMA 2020 guidelines were followed and PubMed, Scopus, Web of Science, and International Symposium of Biomechanics and Medicine in Swimming proceedings databases were searched. Eligibility criteria were defined on the PICOS framework (healthy adolescents in early puberty, swimming programmes or training, passive or active control groups, general effects on physical conditioning or health, longitudinal) and risk of bias was assessed using RoBANS 2. Results: From 2365 records, 20 non-randomized studies met the defined criteria. High heterogeneity in sample size and intervention was observed. While studies related to physical conditioning (<i>n</i> = 5) focused on physiological variables and muscular function, the evidence regarding physical health outcomes (<i>n</i> = 15) explored bone accrual, haemodynamics, body composition, musculoskeletal system, and lung growth. High overall risk of bias (70%) was observed due to strict criteria. Conclusions: Swimming exercise seems to improve cardiorespiratory fitness, cardiac output, haemodynamics, heart growth, motor performance, and body composition of early adolescents. Despite clear evidence that exists on these chronic effects, research on bone health, postural deficit, motor skills, and sleep quality is still missing.

Gang Tan, Jia Li, Jing Xu et al.

Abstract Background There are a few studies on the effectiveness and safety of intravenous administration of tranexamic acid(TXA) in patients who underwent foot and ankle surgery, especially for preoperative hidden blood loss in patients with freshfoot and ankle fractures. Thus, the aim of this study was to investigate whether intravenous administration of different doses of TXA can effectively reduce perioperative blood loss and blood loss before surgery and to determine its safety. Methods A total of 150 patients with fresh closed foot and ankle fractures from July 2021 to July 2023 were randomly divided into a control group (placebo controlled [PC]), standard-dose group (low-dose group [LD], 1 g/24 h; medium-dose group [MD], 2 g/24 h), and high-dose group (HD, 3 g/24 h; ultrahigh-dose group [UD], 4 g/24 h). After admission, all patients completed hematological examinations as soon as possible and at multiple other time points postsurgery. Results There was a significant difference in the incidence of hidden blood loss before the operation between the TXA group and the control group, and the effect was greater in the overdose groups than in the standard-dose groups. There were significant differences in surgical blood loss (intraoperative and postoperative), postoperative HGB changes, and hidden blood loss among the groups. The TXA groups showed a significant decrease in blood loss compared to that of the control group, and the overdose groups had a more significant effect than the standard-dose groups. A total of 9 patients in the control group had early wound infection or poor healing, while only 1 patient in the other groups had this complication, and the difference among the groups was significant. No patients in any group suffered from late deep wound infection, cardiovascular or cerebrovascular events or symptomatic VTE. Conclusion This is the first study on whether TXA can reduce preoperative hidden blood loss in patients with freshfoot and ankle fractures. In our study, on the one hand, intravenous application of TXA after foot and ankle fractures as soon as possible can reduce preoperative blood loss and postoperative blood loss. On the other hand, TXA can also lower wound complications, and over-doses of TXA are more effective than standard doses. Moreover, overdoses of TXA do not increase the incidence of DVT.

Takahiro Maeda, Osamu Obayashi, Muneaki Ishijima et al.

Jaime Rodden, Dolores G. Ortega, Pablo B. Costa

(1) There is growing concern surrounding the adverse effects of prolonged sitting on health, yet its impact on post-exercise recovery remains relatively unexplored. This study aimed to better understand the potential influence of habitual prolonged sitting on recovery time and the unfavorable impact prolonged sitting may have on time to recovery, as assessed by muscle damage and inflammatory markers and an isokinetic dynamometer. (2) Nine college-age men (mean age ± <i>SD</i> = 22.1 ± 3.1 years, body mass = 80.9 ± 15.7 kg, height = 171 ± 9.0 cm, Body Mass Index (BMI) = 27.6 ± 4.9 kg·m²) participated in an exhaustive exercise protocol. Creatine Kinase (CK), Myoglobin (Mb), C-Reactive Protein (CRP), White Blood Cell Count (WBC), Peak Torque (PT), and muscle soreness were measured at baseline and 0, 24, 48, and 72 h post-exercise. Dietary and exercise logs were maintained during the 5-day testing procedure. (3) No significant differences were observed in muscle damage markers (CK [<i>p</i> = 0.068] and Mb [<i>p</i> = 0.128]), inflammatory markers (CRP [<i>p</i> = 0.814] and WBC [<i>p</i> = 0.140]), or PT [<i>p</i> = 0.255]) at any time point. However, a significant positive correlation was found between daily sitting time and the percent increase in CK concentration from 0 h to 72 h (<i>r</i> = 0.738, <i>p</i> = 0.023). Strong correlations were also noted between prolonged sitting and percent change in Mb concentration at 48 h (<i>r</i> = 0.71, <i>p</i> = 0.033) and 72 h (<i>r</i> = 0.889, <i>p</i> = 0.001). There was a significant two-way interaction for time × velocity (<i>p</i> = 0.043) for PT with a simple main effect for time at 60°·<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msup><mrow><mi mathvariant="normal">s</mi></mrow><mrow><mo>−</mo><mn>1</mn></mrow></msup></mrow></semantics></math></inline-formula> (<i>p</i> = 0.038). No significant associations were detected between daily carbohydrate or protein intake and recovery markers (<i>p</i> > 0.05). (4) The findings suggest minimizing daily sitting time may expedite and potentially aid muscle recovery after an intense exercise bout, although further research is warranted to validate these findings.

Michael Schirmer, Johannes Dominikus Pallua

Calcium pyrophosphate deposition disease is known as crowned dens syndrome or peripheral arthritis, especially of knees, hips and shoulders. The disease course is asymptomatic, with acute or chronic disease activity related to osteoarthritis, especially in the elderly. Other risk factors are joint injury, osteoarthritis and metabolic conditions such as primary hyperparathyroidism, hemochromatosis, hypophosphatasia and hypomagnesemia. Genetic background should be considered before the age of 55 years. Only recently was the value of signs and symptoms weighted, allowing the introduction of classification criteria. Biomarkers include compensated polarized light microscopy findings, laboratory values and imaging. Imaging evidence refers to calcification of the fibrocartilage or hyaline cartilage. Chondrocalcinosis defined as such cartilage calcification is most commonly due to calcium pyrophosphate deposition disease. Calcification of the synovial membrane, joint capsule, or tendon should not be scored. Ultrasonography detects calcium pyrophosphate deposits with more than 80% sensitivity rates, which is superior to conventional radiography. In the future, dual-energy computerized tomography and Raman spectroscopy are promising new techniques to assess disease activity. Currently, the primary therapeutic goal is controlling inflammatory reactions and preventing further episodes. However, only hydroxychloroquine and magnesium carbonate have shown some efficacy and reduction of pain intensity so far. As patients report more significant unmet treatment needs than patients with gout, education is an essential issue of care. The new classification criteria will allow the validation of standardized outcome parameters with the definition of remission and low disease activity for developing treat-to-target strategies to perform well-designed interventional trials evaluating new treatment options and strategies.

Zong-Ming Li

Abstract The carpal tunnel is a tightly bounded space, making the median nerve prone to compression and eventually leading to carpal tunnel syndrome. Carpal tunnel release surgery transects the transverse carpal ligament to expand the tunnel arch space, decompress the median nerve, and relieve the associated symptoms. However, the surgical procedure unavoidably disrupts essential anatomical, biomechanical and physiological functions of the wrist, potentially causing reduced grip strength, pillar pain, carpal bone instability, scar tissue formation, and perineural fibrosis. It is desirable to decompress the median nerve without surgically transecting the transverse carpal ligament. This paper is to review several approaches we have developed for nonsurgical carpal arch space augmentation (CASA), namely, radio ulnar wrist compression, muscle-ligament interaction, palmar pulling, and collagenolysis of the transverse carpal ligament. Briefly summarized is the research work on the CASA topic about theoretical considerations, in vitro and in situ experiment, computational modeling, and human subject studies with asymptomatic and carpal tunnel syndrome hands.

David A. O'Connell, Ricki S. Carroll, Angela L. Duker et al.

Abstract The skeletal dysplasias are a heterogeneous group of genetic conditions caused by abnormalities of growth, development, and maintenance of bone and cartilage. Little is known about the roles that cytokines play in the inflammatory and non‐inflammatory pathophysiology of skeletal dysplasia. We sought to test our hypothesis that cytokines would be differentially expressed in children with skeletal dysplasia as compared to typically growing controls. Cytokine levels were analyzed using the Cytokine Human Magnetic 25‐Plex Panel (Invitrogen, Waltham, MA, USA); 136 growing individuals with skeletal dysplasia and compared to a cohort of 275 healthy pediatric control subjects. We focused on the expression of 12 cytokines across nine dysplasia cohorts. The most common skeletal dysplasia diagnoses were: achondroplasia (58), osteogenesis imperfecta (19), type II collagenopathies (11), multiple epiphyseal dysplasia (MED: 9), diastrophic dysplasia (8), metatropic dysplasia (8), and microcephalic osteodysplastic primordial dwarfism type II (MOPDII: 8). Of the 108 specific observations made, 45 (41.7%) demonstrated statistically significant differences of expression between controls and individuals with skeletal dysplasia. Four of the 12 analyzed cytokines demonstrated elevated expression above control levels in all of the dysplasia cohorts (interleukin 12 [IL‐12], IL‐13, interferon γ‐induced protein 10 kDa [IP‐10], regulated on activation, normal T cell expressed and secreted [RANTES]) and two demonstrated expression below control levels across all dysplasia cohorts (monocyte chemoattractant protein 1 [MCP‐1], macrophage inflammatory protein‐1β [MIP‐1β]). The highest levels of overexpression were seen in MOPDII, with expression levels of IP‐10 being increased 3.8‐fold (p < 0.0001). The lowest statistically significant levels of expressions were in type II collagenopathies, with expression levels of MCP‐1 being expressed 0.43‐fold lower (p < 0.005). With this data, we hope to lay the groundwork for future directions in dysplasia research that will enhance our understanding of these complex signaling pathways. Looking forward, validating these early trends in cytokine expression, and associating the observed variations with trends in the progression of dysplasia may offer new candidates for clinical biomarkers or even new therapeutics. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Lu Wang, Ge Yu, Xi Zhang et al.

Abstract Background About 15–60% of individuals with ankle sprains may develop functional ankle instability (FAI), which is characterised by ankle pain, decreased muscle strength, limited range of motion, and impaired balance, causing a decline in social activity and quality of life. However, the relationship between those characters is still unclear. This study aimed to investigate whether a relationship existed between ankle pain, active range of motion (AROM), strength and balance and if ankle pain, AROM and strength can predict balance in individuals with FAI. Methods Seventy-seven subjects (46 males; 31 females) with unilateral FAI participated in this study. Ankle pain was measured by the visual analogue scale (VAS), ankle AROM was measured using a universal goniometer, ankle strength was measured using a handheld dynamometer, the static balance was measured by the Time in Balance Test (TBT) and the dynamic balance was measured by the modified Star Excursion Balance Test (mSEBT). Pearson product-moment correlations were used to determine the correlations between ankle pain, AROM, strength and balance. Multiple linear regressions were used to investigate if ankle pain, AROM and strength can predict balance in individuals with FAI. Results VAS and AROM-plantarflexion predicted 25.6% of the TBT (f2 = 0.344, P < 0.001). AROM-dorsiflexion predicted 24.6% of the mSEBT-anterior reach (f2 = 0.326, P < 0.001). VAS, AROM-plantarflexion and strength-plantarflexion predicted 33.5% of the mSEBT-posteromedial reach (f2 = 0.504, P < 0.001). AROM-plantarflexion and strength-plantarflexion predicted 28.2% of the mSEBT-posterolateral reach (f2 = 0.393, P < 0.001). Conclusion This study shows that ankle plantarflexion strength, AROM of dorsiflexion and plantarflexion and pain are predictors of balance in individuals with FAI. These factors could be considered in the rehabilitation of FAI. Trial registration Trial registration number: ChiCTR2200063532.

Kenneth J Young, Jane Fitzgerald, Jonathan Field et al.

Abstract Background Databases have become an important tool in understanding trends and correlations in health care by collecting demographic and clinical information. Analysis of data collected from large cohorts of patients can have the potential to generate insights into factors identifying treatments and the characteristics of subgroups of patients who respond to certain types of care. The Care Response (CR) database was designed to capture patient-reported outcome measures (PROMs) for chiropractic patients internationally. Although several papers have been published analysing some of the data, its contents have not yet been comprehensively documented. The primary aim of this study was to describe the information in the CR database. The secondary aim was to determine whether there was suitable information available to better understand subgroups of chiropractic patients and responsiveness to care. This would be achieved by enabling correlations among patient demographics, diagnoses, and therapeutic interventions with machine learning approaches. Methods Data in all available fields were requested with no date restriction. Data were collected on 12 April 2022. The output was manually scanned for scope and completeness. Tables were created with categories of information. Descriptive statistics were applied. Results The CR database collects information from patients at the first clinical visit, 14, 30, and 90 days subsequently. There were 32,468 patient responses; 3210 patients completed all fields through the 90 day follow up period. 45% of respondents were male; 54% were female; the average age was 49. There was little demographic information, and no information on diagnoses or therapeutic interventions. We received StartBack, numerical pain scale, patient global impression of change, and Bournemouth questionnaire data, but no other PROMs. Conclusions The CR database is a large set of PROMs for chiropractic patients internationally. We found it unsuitable for machine learning analysis for our purposes; its utility is limited by a lack of demographic information, diagnoses, and therapeutic interventions. However, it can offer information about chiropractic care in general and patient satisfaction. It could form the basis for a useful clinical tool in the future, if reformed to be more accessible to researchers and expanded with more information collected.

Federico Canavese

Karch M. Smith, BA, J. Cade Wheelwright, BS, Garrett V. Christensen, MD et al.

Background: Although nonoperative treatment is effective for degenerative rotator cuff tears (RCTs), it remains unclear whether the delay created by a trial of nonoperative treatment negatively influences the outcome of a subsequent surgical repair. In March 2020, the COVID-19 pandemic resulted in an involuntary delay in the surgical treatment of rotator cuff disease, creating a natural experiment. The purpose of this study was to evaluate the outcomes and healing of patients who underwent delayed surgical treatment of chronic degenerative RCTs as compared with the nondelayed surgical treatment of RCTs. Methods: This was a prospective study of two groups: patients planned to undergo arthroscopic rotator cuff repair between March 16, 2020 and May 1, 2020—the end of the ban on elective surgery—and patients who underwent rotator cuff repair starting six weeks after the ban on elective surgery had been lifted. Preoperatively and at six months postoperatively, we collected the Simple Shoulder Test, the American Shoulder and Elbow Surgeons (ASES) score, and the visual analog scale for pain. We also obtained magnetic resonance imaging (MRI) at six months postoperatively. A power analysis was conducted, and assuming a mean ± standard deviation ASES score of 93.1 ± 13.9 points and a minimum clinically important difference in the ASES score of 27.1 points, 7 patients per group (14 patients in total) would be necessary to have 90% chance of finding a difference. Results: We included 15 patients within each group and obtained 100% follow-up at six months. In the delay group, the mean ± standard deviation delay was 63 ± 24 days. There were no significant preoperative differences between groups in demographics or tear characteristics. Intraoperatively, there were no differences between groups in repair characteristics. Using a repeated-measures analysis of variance, there were significant preoperative vs. postoperative differences in ASES scores (P < .001), visual analog scale scores (P < .001), and Simple Shoulder Test scores (P < .001), but no differences between groups (P = .910, .519, and 0.852, respectively). On MRI, within the delay group, 58% had healed, whereas within the control group, 85% had healed (P = .202). Conclusion: COVID-19 caused a two-month delay in the operative treatment of RCTs. This delay did not significantly alter patient-reported outcomes. This delay resulted in a 27% difference in MRI healing rates, which was not statistically significant in this small study. Larger studies should be conducted as our results suggest that a delay in treatment may negatively impact healing rates.

Darko Jekauc, Sabine Rayling, Sara Klopp et al.

Abstract Background Rehabilitation is seen as crucial in dealing with the demographic change in many European countries. In Germany, for example, after having stayed in a rehabilitation center, patients have the possibility to participate in aftercare programs aimed at promoting long-term health behaviour. Despite the relevance of follow-up support for patients’ long-term health and work ability, participation rates in aftercare programs are quite low. Here, web-based aftercare programs can be a viable alternative to the traditional face-to-face programs due to their flexibility in time and location. This research project aims to use quantitative and qualitative methods to gain more insight into the potential of web-based aftercare programs. Methods The goal is to recruit up to 1150 patients at baseline in five rehabilitation centers across Germany. For ethical reasons, partially randomized experimental study design is used to quantitatively assess the effectiveness of web-based aftercare programs. All patients are offered the traditional face-to-face aftercare treatment (IRENA). When patients deny to participate in traditional face-to-face aftercare, they are randomly distributed into either web-based aftercare (digIRENA) or a control group. In all three groups, the SF-12, which measures subjective health, and the WAI, which measures working ability, will be used at baseline, 13 weeks, 26 weeks and 43 weeks after the patients have left the rehabilitation center. BREQ-2, which measures motivation, is used only in the traditional aftercare group and the web-based aftercare group. A multivariate analysis of variance with repeated measurement and latent growth curve models will be used to compare the development of the variables in the three groups. For the qualitative part of the study, interviews with patients and therapists will be conducted to shed light on the applicability, acceptance, and usability of web-based aftercare programs. Discussion This study may provide valuable insight into the potential of web-based rehabilitation aftercare programs as a way to supplement traditional face-to-face programs. This seems particularly promising if it can manage to reach those patients who do not currently participate in traditional face-to-face rehabilitation aftercare programs due to time and location constraints. Trial registration The trial has been registered at the German Register of Clinical Studies (DRKS) with the registration number: DRKS00022467 .

Mario M. Zaiss, Christopher Hall, Neil W. A. McGowan et al.

Objective The association between inflammation and dysregulated bone remodeling is apparent in rheumatoid arthritis and is recapitulated in the human tumor necrosis factor transgenic (hTNFtg) mouse model. We investigated whether extracellular binding immunoglobulin protein (BiP) would protect the hTNFtg mouse from both inflammatory arthritis as well as extensive systemic bone loss and whether BiP had direct antiosteoclast properties in vitro. Methods hTNFtg mice received a single intraperitoneal administration of BiP at onset of arthritis. Clinical disease parameters were measured weekly. Bone analysis was performed by microcomputed tomography and histomorphometry. Mouse bone marrow macrophage and human peripheral blood monocyte precursors were used to study the direct effect of BiP on osteoclast differentiation and function in vitro. Monocyte and osteoclast signaling was analyzed by Western blotting, flow cytometry, and imaging flow cytometry. Results BiP‐treated mice showed reduced inflammation and cartilage destruction, and histomorphometric analysis revealed a decrease in osteoclast number with protection from systemic bone loss. Abrogation of osteoclast function was also observed in an ex vivo murine calvarial model. BiP inhibited differentiation of osteoclast precursors and prevented bone resorption by mature osteoclasts in vitro. BiP also induced downregulation of CD115/c‐Fms and Receptor Activator of NF‐κB (RANK) messenger RNA and protein, causing reduced phosphorylation of the p38 mitogen–activated protein kinases, extracellular signal–regulated kinases 1/2 and p38, with suppression of essential osteoclast transcription factors, c‐Fos and NFATc1. BiP directly inhibited TNF‐α– or Receptor Activator of NF–κB Ligand (RANKL)–induced NF‐κB nuclear translocation in THP‐1 monocytic cells and preosteoclasts by the canonical and noncanonical pathways. Conclusion BiP combines an anti‐inflammatory function with antiosteoclast activity, which establishes it as a potential novel therapeutic for inflammatory disorders associated with bone loss.

O-Sung Lee, Seung Hoon Lee, Su Jung Mok et al.

Abstract Background It is unclear whether postoperative outcomes are associated with the cartilage regeneration after open wedge high tibial osteotomy (OWHTO) combined with microfracture. The purpose of this study was to evaluate the regeneration of the articular cartilage, radiologic, and clinical outcomes after OWHTO with and without microfracture. Methods Eighty-seven patients who underwent OWHTO from 2014 to 2015 were retrospectively included in this study. Fifty-seven OWHTOs with microfracture on medial femoral condyle (MFC) (group 1) and 30 OWHTOs without microfracture (group 2) were compared at a mean 2-year follow-up. The regeneration of the articular cartilage was evaluated using International Cartilage Repair Society (ICRS) grade on the second-look arthroscopy and the magnetic resonance observation of cartilage repair tissue (MOCART) score on magnetic resonance imaging (MRI). The weight-bearing line (WBL) ratio, hip-knee-ankle (HKA) angle, joint line convergence angle (JLCA) and Ahlbäck grade were evaluated. The clinical outcomes were evaluated using the Western Ontario and McMaster University (WOMAC) scores and the Knee Society (KS). Results The articular cartilage in the MFC were regenerated in 67.8% of group 1 (43/57) and 58.6% of group 2 (16/30), respectively (p = 0.014). However, change of the ICRS grades of the medial tibial plateau, lateral and patellofemoral compartments showed no statistical difference between the groups. Total MOCART score in group 1 was superior to that in the group 2 at postoperative 2 years (41.8 ± 18.6 vs. 31.8 ± 19.8, p = 0.023). Regarding MOCART score, microfracture was only effective in the defect filling and integration to the border zone of the MFC (p < 0.001 and p = 0.035, respectively). Other radiologic and clinical outcomes showed no statistical differences between the groups. Conclusion Microfracture of the MFC during OWHTO only helped the filling of the degenerative cartilage defect and the integration of the cartilage with adjacent cartilage. However, the clinical and radiologic outcome could not be improved by mircrofracture in the OWHTO.

Dora Montiel Jarolin, Patricia Sobarzo

Introducción: La hemorragia alveolar difusa (HAD) sigue siendo una complicación pulmo- nar poco frecuente del lupus eritematoso sistémico (LES), pero potencialmente mortal me parece que así quedaría mejor. Objetivo: presentar las características clínicas, tratamiento y la evolución de dos pacientes con LES con hemorragia alveolar y nefritis lupica asociada como forma de debut del LES. Material y Método: serie de dos casos de pacientes con diagnóstico de LES con hemor- ragia alveolar difusa como forma de debut del LES, internadas en el Departamento de Medicina interna del Hospital Nacional de itaugua en el periodo 2007-2018. Resultados: de 500 pacientes con LES en seguimiento, 2 mujeres presentaron hemo- rragia alveolar como forma de debut del LES (0,4%), edad media 22 años ± 4,2., tiempo  de enfermedad media de 60 días ± 42,4. Ambas pacientes presentaron disnea, fiebre, hemoptisis, disminución de la Hb, infiltrado pulmonar bilateral en la Radiografía de tórax, nefritis, insuficiencia respiratoria aguda, asistencia respiratoria mecánica (ARM). Solo una paciente se realizó biopsia renal, NL clase 3/C. Así mismo las dos pacientes recibieron pulsos de metilprednisolona 1g/d/3 días, seguidas de ciclofosfamida, con buena respuesta al tratamiento en una paciente y un óbito en la otra paciente. Comentario: Ambas debutaron con HAD, presentaron nefropatía asociada y necesidad  de asistencia respiratoria mecánica. El óbito se presentó en la paciente con nefropatía e insuficiencia renal aguda.