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To investigate differences in proprioception using four proprioceptive tests in children with and without hypermobility. Additionally, it was tested if the results on one proprioceptive test predict the results on the other tests. Of the children (8-11years), 100 were classified as normal mobile (Beighton score 0–4) and 50 as hypermobile (Beighton score 5–9). To test proprioception, in the upper extremity the unilateral and bilateral joint position reproduction tasks were used and for the lower extremity the loaded and unloaded wedges task. No differences were found in any of the proprioception tests between the two groups. Estimating the height of the wedges was easier in the loaded position (mean penalty in standing and sitting position, 4.78 and 6.19, respectively). Recalling the elbow position in the same arm resulted in smaller errors compared to tasks reproducing the position with the contralateral arm. Of the four angles used (110°, 90°, 70°, 50°), the position recall in the 90° angle had the smallest position error (1.8°). Correlations between the proprioception tests were weak (Loaded and Unloaded (r 0. 28); Uni and Bilateral (r 0.39), Upper and Lower extremity not significant). No indication of poorer proprioception was found in children with hypermobile joints compared to their normal mobile peers. Loading gives extra information that leads to fewer errors in the wedges task performed while standing, but this effect is independent of joint mobility. Proprioception test outcomes are dependent on the test used; upper extremity results do not predict lower extremity outcomes or vice versa. [ABSTRACT FROM AUTHOR]

Background: Many patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC. Methods: Patients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys. Results: In this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p < 0.001), neurological (92.4% vs. 15.4%, p < 0.001), sleep (82.8% vs. 5.3%, p < 0.001), skin (69.8% vs. 0%, p < 0.001), and genitourinary (60.6% vs. 25.0%, p = 0.029) issues. 58% of LC patients screened positive for ME/CFS vs. 0% of controls (p < 0.001), 27% positive for GJH compared to 10% of controls (p = 0.026), and a positive average score of 4.0 on orthostatic intolerance vs. 0 (p < 0.001). The majority of LC patients with ME/CFS were women (77%). Conclusion: We found that comorbidities across 12 surveyed categories were increased in patients following SARS-CoV-2 infection. Our data also support the overlap of LC with ME/CFS, GJH, and orthostatic intolerance. We discuss the pathophysiologic, research, and clinical implications of identifying these conditions with LC. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Level of Evidence To determine whether there is a correlation between preoperative coronal varus or valgus laxity and patient‐reported outcome measures (PROMs) 2 years after individualised total knee arthroplasty (TKA).Records of 150 consecutive patients who received individualised TKA were retrospectively analysed, and 126 with complete pre‐ and postoperative data were included. Preoperative coronal varus and valgus stress radiographs (15 N load) were taken using a telos stress device with the knee in 5°–10° of flexion. Varus stress angles were positive if the joint opened on the lateral side, and valgus stress angles were positive if the joint opened on the medial side. The sum of varus and valgus stress angles indicated total joint laxity. During surgery, cases that required tibial recuts to balance the joint were recorded. Patients completed three PROMs and rated their satisfaction. Correlations between laxity and PROMs were evaluated using Pearson's correlation.Stress radiographs revealed varus stress angles of 6.3° ± 3.5° (range, −4.5° to 14.1°), valgus stress angles of 0.1° ± 3.7° (range, −8.0° to 10.9°), and the sum of the varus and valgus stress angle of 6.4° ± 3.3° (range, 0.1° to 17.1°). There were no correlations between laxity and PROMs: r < 0.160 for varus stress angle, r < 0.180 for valgus stress angle and r < 0.160 for the sum of stress angles. There were no statistically significant or clinically relevant differences in PROMs between knees without and those with tibial recuts.Preoperative coronal varus or valgus laxity was not correlated with PROMs following individualised TKA at a minimum 2‐year follow‐up. Individualised TKA with personalised alignment enables adequate accommodation of a broad spectrum of preoperative coronal varus–valgus laxities.IV [ABSTRACT FROM AUTHOR]

INTRODUCTION: We examined autoimmunity markers (AIM) and autonomic dysfunction in patients with chronic neurogastroenterological symptoms and their relationship to joint hypermobility/hypermobility spectrum disorder (JH/HSD). METHODS: AIM positivity was defined as a diagnosis of known autoimmune/autoinflammatory disorder with at least 1 positive seromarker of autoimmunity or at least 2 positive seromarkers by themselves. Three cohorts were studied: (i) retrospective (n = 300), (ii) prospective validation cohort (n = 133), and (iii) treatment cohort (n = 40), administered open-label intravenous immunoglobulin (IVIG). RESULTS: AIM positivity was found in 40% and 29% of the retrospective and prospective cohorts, the majority of whom (71% and 69%, respectively) had autoinflammatory disorder. Significantlymore patients with AIM had elevations of C-reactive protein (31% vs 15%, P < 0.001) along with an increased proportion of cardiovascular autonomic dysfunction (48% vs 29%; P < 0.001), small fiber neuropathy (20% vs 9%; P = 0.002), and HLADQ8 positivity (24% vs 13%, P = 0.01). Patients with JH/HSD were more likely to have AIM (43% vs 15%, P = 0.001) along with more severe autonomic and gastrointestinal (GI) symptom scores. IVIG treatment was associated with robust improvement in pain, GI, and autonomic symptoms, but adverse events were experienced by 62% of patients. DISCUSSION: Autoimmune markers and autonomic dysfunction are common in patients with unexplained GI symptoms, especially in those with JH/HSD. Many patients seem to respond to IVIG treatment, but this needs to be confirmed by controlled trials. These results highlight the need for vigilance for autoimmune and autonomic factors and JH/HSD in patients with neurogastroenterological disorders. Clinicaltrials. gov, NCT04859829. [ABSTRACT FROM AUTHOR]

Hypoglycemia in the absence of diabetes is often multifactorial and challenging to diagnose definitively. We present a case report and an expanded series of adult females with reactive hypoglycemia who were diagnosed with Ehlers-Danlos syndrome (EDS). These patients exhibited predominantly postprandial hypoglycemia, with some fasting and activity-induced episodes. Clinical findings included autonomic dysfunction, gastrointestinal symptoms, and joint hypermobility. Interventions focused on medical nutrition therapy, continuous glucose monitoring, and, in some cases, medication. Many patients continued to experience hypoglycemic episodes despite treatment. Key learning points include the potential association between hypermobile EDS and hypoglycemia, the importance of confirming the Whipple triad, and the need for multidisciplinary management. This case series highlights the need for further research into the prevalence and pathophysiology of hypoglycemia in EDS. [ABSTRACT FROM AUTHOR]

Purpose: To assess the outcomes of medial patellofemoral ligament (MPFL) reconstruction using synthetic suture tape in paediatric patients with patellofemoral instability (PFI). Methods: This ambispective comparative study, conducted from 2014 to 2022, included paediatric patients who underwent MPFL reconstruction with synthetic suture tape and had a minimum follow‐up of 1 year. Pre‐ and postoperative clinical and functional outcomes, patient satisfaction and complications were assessed. Results: The study comprised 22 patients (29 knees), with a median age at surgery of 14.4 years (interquartile range [IQR] 10.9–16.7) and a median follow‐up of 46.5 months (24.7–66). Notably, 13 knees (44.8%) had open growth plates at the time of surgery. The cohort included patients with Down syndrome (3 patients), Ehlers‐Danlos (2), arthrogryposis (1), generalized joint hypermobility (8) and previous unsuccessful PFI surgeries (8). Concomitant procedures were performed on 16 knees. Postoperatively, improvements were observed in all but one patient, who reported residual pain. There were two other complications: one suture‐tape rupture and one surgical wound infection. Functional scores significantly improved: Kujala, +14 points (7–29) (p < 0.001); IKDC, +10.5 points (5.2–25.3) (p < 0.001); Tegner, +2 points (0–4) (p < 0.001); Lysholm, +15 points (0–37.5) (p < 0.001). Most patients achieved excellent outcomes by Crosby‐Insall criteria (21 patients, 72.4%) and reported high satisfaction (23 patients, 79.3%). Conclusions: MPFL reconstruction using synthetic suture tape is a viable and effective treatment for paediatric patients with PFI, particularly for those with connective tissue disorders, generalized joint hypermobility or past surgical failures, significantly enhancing clinical and functional outcomes with an acceptable complication rate. Level of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

Background: Juvenile idiopathic arthritis (JIA) is common in pediatric rheumatology. Despite treatment, many patients experience persistent disease activity. Joint hypermobility (JH), defined by an excessive range of motion across multiple joints, is prevalent in children and adolescents and may influence disease outcomes in JIA. Objective: This study examines the impact of JH on symptoms in youth and young adults with JIA. Methods: Data were obtained from the PR-COIN network and included patients under 21 years old with a diagnosis of JIA. Patients with JIA and JH were matched with those having JIA-only based on age, sex assigned at birth, JIA subtype, and medication exposure. Clinical data, including disease activity measures, patient well-being, and pain ratings, were collected at baseline and follow-up visits. Results: The sample included 420 patients with JIA + JH and 2100 with JIA only. The JIA + JH group exhibited higher disease activity at baseline, more active arthritis joints, elevated physician global assessment of disease activity scores, and worse patient-reported well-being. These differences persisted over time. The JIA + JH group had a 19–20% greater likelihood of maintaining high disease activity scores and worsening over subsequent visits, indicating a significant impact of JH on disease progression. Conclusion: JH in youth with JIA is associated with higher and persistent disease activity, suggesting that JH significantly contributes to the disease burden in patients with JIA and should be considered in treatment strategies. Future research should further explore the mechanisms by which JH influences disease activity and investigate comprehensive management approaches to improve outcomes for this population. Key Points • Children with JIA and joint hypermobility (JH) exhibit significantly higher disease activity at baseline compared to those with JIA only, including more active arthritis joints and elevated physician global assessment scores. • The presence of JH in JIA patients is associated with poorer patient-reported well-being and higher overall disease activity scores, which persist over time despite treatment. • JIA + JH patients have a 19–20% greater likelihood of maintaining high disease activity and worsening over subsequent visits, indicating a significant impact of JH on disease progression. • The study suggests that JH should be considered an important clinical factor in the management of JIA, with targeted interventions needed to address the increased disease activity and improve overall patient outcomes. [ABSTRACT FROM AUTHOR]

Patients with joint-hypermobility and joint-hypermobility spectrum disorders (HSD), including hypermobile Ehlers-Danlos Syndromes (EDS) present numerous co-morbid concerns, and multidisciplinary care has been recommended. The complexity of these patient's needs and increased demand for medical services have resulted in long delays for diagnosis and treatment and exhausted extant clinical resources. Strategies must be considered to ensure patient needs are met in a timely fashion. This opinion piece discusses several potential models of care for joint-hypermobility disorders, several ways in which primary providers can be involved, and argues that primary providers should be an essential and integrated part of the management of these patients, in collaboration with multidisciplinary teams and pediatric subspecialists. We review several strategies and educational opportunities that may better incorporate primary providers into the care and management of these patients, and we also discuss some of the limitations and barriers that need to be addressed to improve provision of care. This includes establishing primary care physicians as the medical home, providing initial diagnostic and treatment referrals while connecting patients with specialty care, and collaboration and coordination with multi-disciplinary teams for more complex needs. Several barriers exist that may hamper these efforts, including a lack of available specialty trainings for providers interested in providing care to patients with EDS and HSD, a lack of expertly derived consensus guidelines, and limited time resources in extant primary care practices. Also, primary providers should have an active voice in the future for the further consideration and development of these presented strategies. [ABSTRACT FROM AUTHOR]

Measures of manganese (Mn) status in cattle vary among studies, and no single criterion accurately predicts or diagnoses Mn deficiency and pathologic outcomes. Mn deficiency causes congenital joint laxity and dwarfism (CJLD) when total dietary intake is <20 ppm Mn dry matter (DM) for most of the pregnancy. However, the recommended dietary intake of 40 ppm DM can also result in clinical Mn deficiency. Some studies have found that CJLD occurs in calves from cows fed red clover or silage but not in calves from cows fed hay. The concentration of Mn in the liver is the best indicator of Mn status in neonates and adults but cannot be interpreted in fetuses. Serum, plasma, and whole blood concentrations of Mn are unreliable indicators of bovine Mn status. The primary objective of our report is to present evidence linking CJLD to a primary or secondary Mn deficiency. To predict and diagnose Mn deficiency in cattle, we propose using a combination of clinical signs, dietary Mn, liver Mn at birth and beyond, positive response to Mn supplementation or the replacement of silage with other forages, and ruling out other causes of malformations. By following these recommendations, we expect that CJLD and gestational death will decrease as hepatic Mn concentrations increase at birth. Many publications we reviewed are not statistically sound, and future research should include a statistician from the initial discussions of the study through the final publication. [ABSTRACT FROM AUTHOR]

The development of the ulnar collateral ligament (UCL) guideline was undertaken in accordance with the British Society for Surgery of the Hand Evidence for Surgical Treatment (BEST) Process Manual, which has been accredited by the National Institute for Health and Care Excellence, UK. This review article serves as a summary of the systematic reviews and the final guideline. The group included two patients, a radiologist, a commissioner, an emergency medicine doctor, hand therapists and hand surgeons. The group's recommendations are that patients with acute UCL injuries should be assessed with a history, clinical examination and radiographs. Patients without significant joint laxity can be treated non-surgically. Patients with significant joint laxity on clinical examination may be treated with non-surgical joint immobilization or surgical repair and should reach a shared decision with their clinician about the definitive treatment within 2 weeks of presentation. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the characteristics of balance and gait functions in Generalized Joint Hypermobility (GJH) subjects residing in high-altitude areas. Methods: This study included 61 university students (28 with GJH and 33 healthy controls) all from the high-altitude region of Linzhi, Tibet Autonomous Region. The Riablo™ wearable intelligent rehabilitation assessment and training system was used to assess static balance (with eyes open and closed) and gait function (during flat walking) in both groups. Results: Compared to healthy subjects, GJH subjects exhibited significantly impaired balance, indicated by an increased distance of the center of pressure position from the ideal center of gravity(EO: P = 0.007, EC: P = 0.031) and greater amplitude of center of pressure displacements (EO: P = 0.043, EC: P = 0.032). Gait velocity(P = 0.007), stride length(P = 0.012), and swing stance phase of the gait cycle(P = 0.046) were significantly reduced in GJH subjects compared to healthy subjects. A significant increase in the flat-foot phase of the gait cycle(P = 0.022) was observed in GJH subjects compared to healthy subjects. Conclusion: The current study demonstrated that GJH subjects residing in high-altitude areas exhibit impairments in balance and gait, providing a basis for training and prevention strategies tailored for this population. And this study used the wearable intelligent rehabilitation evaluation and training system in high-altitude areas, providing methodological references for scientific research on balance and gait function under non laboratory conditions. Trial registration: Controlled Trials No.102772023RT133, Registered 13 October 2023. [ABSTRACT FROM AUTHOR]

Aim Method Results Interpretation To describe what is known about hip problems in individuals with developmental central hypotonia.Searches were conducted in five databases to October 2023. Down syndrome was excluded from this analysis of less well‐known genetic diagnoses. At least two reviewers independently screened titles, abstracts, read full‐text articles, and extracted data.Of 89 full‐text articles, 79 met inclusion criteria. Studies included 544 individuals aged 1 month to 63 years with Kabuki, 49, XXXXY, Prader–Willi, PURA, Koolen de Vries, Emanuel, TRPM3, Wolf–Hirschhorn, and other rare syndromes. Most diagnoses may be associated with a combination of differences in hip structure or stability that are evident at birth, or develop in early infancy, with increasing hip dysplasia and subluxation over time. Joint or ligamentous laxity was most reported along with hypotonia and hypermobility as risk factors. Limited data were identified about conservative or surgical intervention and outcomes in these populations.Children with significant hypotonia, with or without a confirmed genetic diagnosis, are at increased risk of hip problems that may be missed with standard neonatal screening. Ultrasound is recommended between 6 weeks and 6 months, and annual orthopaedic review with regular radiographs for older children and adults with significant and persistent hypotonia. [ABSTRACT FROM AUTHOR]

BackgroundPurposeMethodsResultsConclusionComparisons of talar cartilage and the anterior talofibular ligament (ATFL) profiles in individuals with different levels of chronic ankle instability (CAI) provide insight into early adaptation of tissue morphology.This study compared morphologic response and recovery of the talar cartilage and ATFL before and after 30-min of self-paced treadmill running between individuals with CAI, coper (full recovery from a first-time ankle sprain), and healthy controls.Sixty young males (24.8 years, 176.9 cm, 75.7 kg) were allocated into the CAI, coper, and healthy control group by their number of ankle sprains and scores on the self-reported ankle instability questionnaires (Cumberland Ankle Instability Tool, and Foot and Ankle Ability Measure-Activities of Daily Living). Ultrasonographic images in the cross-sectional area (CSA; overall, lateral, and medial) and ATFL length (unstressed and stressed and position) before and after treadmill running were recorded and analyzed.There were no group by time interactions in the talar cartilage CSA (F14,399 <1.09, p > .36 for all tests) and ATFL length (F14,399< .69, p > .79 for all tests). Regardless of time, CAIs had the largest overall (F2,399 = 42.68, p < .001), lateral (F2,399 = 37.16, p < .001), and medial (F2,399 = 36.57, p < .001) CSA of talar cartilage and the longest stressed-ATFL length (F2,399 = 54.42, p < .001), followed by copers and healthy controls.Morphologic features of the talar cartilage and ATFL appear to depend on the level of ankle instability (e.g. a history of recurrent ankle sprain). [ABSTRACT FROM AUTHOR]

This study aims to examine the effects of different attention focuses on muscle strength and balance performance in individuals with Generalized Joint Hypermobility (GJH). This randomized crossover trial included 32 individuals with GJH whose Beighton score was greater than 5. Subjects performed each task under external attentional focus, internal attentional focus, and neutral attentional focus condition. Knee extensor muscle strength was measured using the Isokinetic Dynamometer. Postural stability was evaluated using the Biodex Balance System, while dynamic balance was assessed using the Y Balance Test. The main effects of attentional focus on the outcomes were analyzed using repeated measures ANOVA and post-hoc corrections with a 95% confidence interval. Subjects produced significantly higher quadriceps peak torque during external focus instruction and internal focus instruction compared to neutral condition (p = .006). Postural stability performance were found to be better during external attention focus compared to the internal focus of attention and the neutral group (p = .008). In addition, an increase in Y balance composite score was observed during external condition compared to internal condition and neutral condition (p < .001). Whether internal or external, the use of attentional focus may be beneficial for optimal force production during training in individuals with GJH. External attention focus enabled better postural stability and dynamic balance performances. [ABSTRACT FROM AUTHOR]

The article focuses on an 11-year-old boy presenting with slurred speech and involuntary movements, later diagnosed with a neurological disorder. Topics include his clinical symptoms such as dysarthria and abnormal involuntary movements, his physical exam findings including hyperreflexia and abnormal gait, and the absence of significant prior medical or family history.

In the realm of research, the single case study has been recognized as a valuable tool for sharing insights, demonstrating new concepts, discovering novel phenomena, consolidating hypotheses, and sparking original ideas. In this physician-guided narrative, phenomena previously unreported in the clinical context are explored. These case studies aim to offer insights that may inform an existing theoretical model that encapsulates a distinct therapeutic intervention. Original research in fascia-focused therapies presents many challenges, including the lack of universal terminology, inconsistent techniques, and difficulties in quantifying treatment effects. Tensegrity-based approaches, which concentrate on tissue tension, also face challenges in establishing their validity within living organisms. For centuries, fascia was seen only as ribbons and sheets of soft, inert, mostly fatty tissue. Consequently, most anatomy textbooks provide a sterile view of anatomical structures devoid of the context of unifying fascia. Now, however, consensus of research describes fascia as an omnipresent, ubiquitous, body-wide tissue that acts as a system, transmitting mechanical information via tensional force changes. The clinical outcomes in the cases provided in this narrative report suggest that induction of thigh fascia resulted in immediate anatomically distant therapeutic benefit, as reported by the patients. Rather than measuring treatment efficacy, these two case studies utilize a specific myofascial induction performed at high velocity to elucidate the possibility of a fascia-based, tensegrity-mediated, mechanism for commonly managed, yet often incurable conditions – Benign Paroxysmal Positional Vertigo (BPPV) symptoms and Temporomandibular Joint (TMJ) pain (within the spectrum of Temporomandibular Disorder (TMD)). [ABSTRACT FROM AUTHOR]

Background: Ehlers-Danlos syndrome (EDS) is a hereditary disease characterised by joint hypermobility, skin hyperextensibility and tissue fragility. Hypermobile EDS (hEDS is the more frequent subtype. Joint surgery may benefit certain patients after failure of medical treatments, but there is no consensus on the optimal surgical management of patients with hEDS. The aims of this retrospective study were to chart the surgical management of patients with hEDS, to determine the role of arthroscopy and to evaluate the functional results of joint surgery, including the reintervention rates. Results: A total of 69 patients with non-vascular EDS were evaluated (60 female; 87%). Mean (SD) age at first surgery was 25.6 ± 11.1 years. Among the 69 patients, first surgeries were carried out on the knee (n = 50; 39.4%), ankle (n = 28; 22.0%), shoulder (n = 22; 17.3%), wrist (n = 18; 14.2%) and elbow (n = 9; 7.1%). One-fifth of all first operations (20.8%) were carried out by arthroscopy, most often on the knee (36% of knee surgery cases). At the time of primary surgery, the surgeon was alerted to the diagnosis or suspicion of hEDS in only 33.9% of patients. The rate of reoperations (2 to ≥ 5) was 35.7% (10/28) for the ankle, 40.9% (9/22) for the shoulder, 44.4% (4/9) for the elbow, 50% (9/18) for the wrist and 60% (30/50) for the knee. Local or regional anaesthesia was badly tolerated or ineffective in 27.8%, 36.4% and 66.6% of operations on the wrist, shoulder and elbow, respectively. Overall, the majority of patients (> 70%) were satisfied or very satisfied with their surgery, particularly on the non-dominant side. The lowest satisfaction rate was for shoulder surgery on the dominant side (58.3% dissatisfied). Conclusions: Surgery for joint instability has a greater chance of success when it is carried out in patients with a known diagnosis of EDS before surgery. The majority of patients were satisfied with their surgery and, with the exception of the knee, there was a low rate of reoperations (≤ 50%). Arthroscopic procedures have an important role to play in these patients, particularly when surgery is performed on the knee. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions Level of Evidence Intraoperative laxity assessments in total knee arthroplasty (TKA) are subjective, with few studies comparing against standardised preoperative and postoperative assessments. This study compares coronal knee laxity in TKA patients awake and anaesthetised, preprosthesis and postprosthesis implantation, evaluating relationships to patient‐reported outcome measures.A retrospective analysis of 49 TKA joints included preoperative and postoperative computed tomography scans, stress radiographs and knee injury and osteoarthritis outcome score (KOOS) questionnaire results preoperatively and 12 months postoperatively. The imaging was used to assess functional laxity (FL) in awake patients, whereas computer navigation measured intraoperative surgical laxity (SL) preimplantation and postimplantation, with patients anaesthetised. Varus and valgus stress states and their difference, joint laxity, were measured.SL was greater than FL in both preimplantation [8.1° (interquartile range, IQR 2.0°) and 3.8° (IQR 2.9°), respectively] and postimplantation [3.5° (IQR 2.3°) and 2.5° (IQR 2.7°), respectively]. Preimplantation, SL was more likely than FL to categorise knees as correctable to ±3° of the mechanical axis. Preoperative FL correlated with KOOS Symptoms (r = 0.33, p = .02) and quality of life (QOL) (r = 0.38, p = .01), whereas reducing medial laxity with TKA enhanced postoperative QOL outcomes (p = .02).Functional coronal knee laxity assessment of awake patients is generally lower than intraoperative surgical assessments of anaesthetised patients. Preoperative SL may result in overcorrection of coronal TKA alignment, whereas preoperative FL better predicts postoperative patient outcomes and reflects the patients' native and tolerable knee laxity. Preoperative FL assessment can be used to guide surgical planning.Level II. [ABSTRACT FROM AUTHOR]

Background: Human patients with Ehlers‐Danlos syndrome (EDS) are categorized into subtypes based on causative genetic variants and phenotypes. The classical form of EDS, primarily caused by variants in COL5A1 or COL5A2, is a very common subtype in people but is poorly characterized in dogs. Objective: Describe likely causal COL5A1 variants in dogs with classical EDS, summarize clinical histories, discuss potential disease mechanisms, and draw conclusions about disease prognosis. Animals: Seven client‐owned dogs that exhibited clinical signs of classical EDS. Methods: Clinical information was recorded from medical records and communication with attending veterinarians and dog owners. To identify potential causal gene sequence variants whole‐genome sequence analyses (n = 6) or Sanger sequencing (n = 1) were performed on DNA isolated from the probands. Pathological abnormalities in skin biopsy samples were assessed using histology and electron microscopy in 3 dogs. Results: Six distinct heterozygous COL5A1 sequence variants were identified. The most common clinical signs included fragile skin (n = 7), hyperextensible skin (n = 7), joint hypermobility (n = 6), and atrophic scars (n = 5). The median age at last follow‐up or death was 12 years (range, 6.5‐14 years). Ultrastructural abnormalities in dermal collagen differed among dogs with different COL5A1 variants. Conclusion and Clinical Importance: We describe the genotypic and phenotypic spectrum of the classical subtype of EDS by identifying 6 novel COL5A1 variants in conjunction with detailed clinical histories that included long‐term follow‐up information in 7 dogs. [ABSTRACT FROM AUTHOR]

Skeletal disorders encompass a wide array of conditions, many of which are associated with short stature. Among these, Desbuquois dysplasia is a rare but severe condition characterized by profound dwarfism, distinct facial features, joint hypermobility with multiple dislocations, and unique vertebral and metaphyseal anomalies. Desbuquois dysplasia is inherited in an autosomal recessive manner, with both the DBQD1 (MIM 251450) and DBQD2 (MIM 615777) forms resulting from biallelic mutations. Specifically, DBQD1 is associated with homozygous or compound heterozygous mutations in the CANT1 gene, while DBQD2 can result from mutations in either the CANT1 or XYLT1 genes. This review synthesizes the findings of 111 published case reports, including 54 cases of DBQD1, 39 cases of DBQD2, and 14 cases of the Kim variant (DDKV). Patients in this cohort had a median birth weight of 2505 g, a median length of 40 cm, and a median occipitofrontal circumference of 33 cm. The review highlights the phenotypic variations across Desbuquois dysplasia subtypes, particularly in facial characteristics, joint dislocations, and bone deformities. Genetic analyses revealed a considerable diversity in mutations, with over 35% of cases involving missense mutations, primarily affecting the CANT1 gene. Additionally, approximately 60% of patients had a history of parental consanguinity, indicating a potential genetic predisposition in certain populations. The identified mutations included deletions, insertions, and nucleotide substitutions, many of which resulted in premature stop codons and the production of truncated, likely nonfunctional proteins. These findings underscore the genetic and clinical complexity of Desbuquois dysplasia, highlighting the importance of early diagnosis and the potential for personalized therapeutic approaches. Continued research is essential to uncover the underlying mechanisms of this disorder and improve outcomes for affected individuals through targeted treatments. [ABSTRACT FROM AUTHOR]

OBJECTIVE Evaluate whether total elbow replacement (TER) through a lateral approach is accurate and stable. ANIMALS 12 skeletally mature large-breed dog cadavers were used. METHODS Limb alignment, elbow joint motion, and collateral ligament laxity were evaluated preoperatively. The order of surgery (left or right) and the approach (lateral or medial) were randomly selected for TER in each dog. The other approach was used in the contralateral elbow. Intraoperative technical difficulties, duration of surgery, and anatomic complications were recorded. Limb alignment, elbow joint motion, collateral ligament laxity, and prosthetic component alignment were evaluated after surgery. Data were collected from June 11 to 15, 2023. RESULTS The duration of surgery using a lateral or medial approach did not differ (P = .499). Anatomic complications were not observed. The lateral approach resulted in 8° more elbow extension (P = .003), 1.58° less lateral collateral ligament constraint (P = .033), 2.80° less medial collateral ligament constraint (P = .002), 4.38° less frontal plane constraint (P = .004), 8° greater humeral component inclination (P = .033), and 5.6° greater radioulnar component varus (P = .001) than the medial approach. Varus of the radius, mechanical axis deviation, limb supination, elbow flexion, mediolateral humeral component and craniocaudal radioulnar component orientation did not differ among joints operated using a lateral or medial approach. In normal cadaveric elbows, a lateral approach for TER appears feasible, producing equivalent limb alignment, joint laxity, and joint motion to normal elbows and to TER placed using a medial approach. CLINICAL RELEVANCE In dogs, TER can be performed using a lateral surgical approach. [ABSTRACT FROM AUTHOR]

Ehlers–Danlos syndromes (EDS) are a group of multisystemic conditions that share soft and hyperextensible skin, abnormal wound healing, easy bruising, joint hypermobility, and chronic pain, with variable involvement of cardiovascular, musculoskeletal, and ocular systems. Alterations in collagen fibril morphology and organization are a unifying feature in all EDS types, despite a diverse range of underlying disease genes and molecular defects. A change in integrin receptors is found on the surface of dermal fibroblasts in most EDS types. Emerging insights from transcriptome profiling studies highlight a role for disturbed intracellular signaling pathways in some EDS types, such as the unfolded protein response (UPR) and impaired transforming growth factor β (TGFβ) signaling. The complete range of molecular mechanisms contributing to the pleotropic phenotype and the connection between different EDS types are incompletely understood. The Ehlers–Danlos syndromes (EDS) are a group of rare heritable connective tissue disorders, common hallmarks of which are skin hyperextensibility, joint hypermobility, and generalized connective tissue fragility. Currently, 13 EDS types are recognized, caused by defects in 20 genes which consequently alter biosynthesis, organization, and/or supramolecular assembly of collagen fibrils in the extracellular matrix (ECM). Molecular analyses on patient samples (mostly dermal fibroblast cultures), combined with studies on animal models, have highlighted that part of EDS pathogenesis can be attributed to impaired cellular dynamics. Although our understanding of the full extent of (extra)cellular consequences is still limited, this narrative review aims to provide a comprehensive overview of our current knowledge on the extracellular, pericellular, and intracellular alterations implicated in EDS pathogenesis. The Ehlers–Danlos syndromes (EDs) are a group of rare heritable connective tissue disorders, common hallmarks of which are skin hyperextensibility, joint hypermobility, and generalized connective tissue fragility. Currently, 13 EDS types are recognized, caused by defects in 20 genes which consequently alter biosynthesis, organization, and/or supramolecular assembly of collagen fibrils in the extracellular matrix (ECM). Molecular analyses on patient samples (mostly dermal fibroblast cultures), combined with studies on animal models, have highlighted that part of EDS pathogenesis can be attributed to impaired cellular dynamics. Although our understanding of the full extent of (extra)cellular consequences is still limited, this narrative review aims to provide a comprehensive overview of our current knowledge on the extracellular, pericellular, and intracellular alterations implicated in EDS pathogenesis. [ABSTRACT FROM AUTHOR]

Knee collateral ligaments play a vital role in providing frontal-plane stability in post-total knee arthroplasty (TKA) knees. Finite element models can utilize computationally efficient one-dimensional springs or more physiologically accurate three-dimensional continuum elements like the Holzapfel-Gasser-Ogden (HGO) formulation. However, there is limited literature defining subject-specific mechanical properties, particularly for the HGO model. In this study, we propose a co-simulation framework to obtain subject-specific material parameters for an HGO-based finite element ligament model integrated into a rigid-body model of the post-TKA knee. Our approach achieves comparable accuracy to spring formulations while significantly reducing coefficient calibration time and demonstrating improved correlation with reference knee kinematics and ligament strains throughout the tested loading range. [ABSTRACT FROM AUTHOR]

An 11-month-old Border Collie dog presented with recurrent fever since the age of 3 months. Clinical examination revealed stunted growth, facial dysmorphism, fever, oral and third eyelid ulcerations and stiff gait with tarsal hyperlaxity. Clinicopathologic testing revealed neutropenia with normal neutrophil maturation in the bone marrow, ulcerative neutrophilic stomatitis and glossitis and a nonperforating duodenal ulcer. Genetic testing showed a mutation in the vacuolar protein sorting-associated protein 13B gene, establishing a diagnosis of trapped neutrophil syndrome. Steroid therapy was not prescribed due to the presence of a duodenal ulcer. Two weeks later, antibiotics and omeprazole facilitated a mild clinical improvement with relapse; euthanasia was subsequently elected. This case highlights clinical signs not previously described in dogs but known in humans with Cohen syndrome, including buccal ulcerations or joint hyperlaxity. This is also the first description of this disease in France, where Border Collies are commonly bred. [ABSTRACT FROM AUTHOR]

Background: Dermatofibromas, also known as benign fibrous histiocytomas, are among the most common cutaneous soft-tissue lesions. Association of multiple dermatofibromas with some diseases was described and it has not been reported with Ehlers–Danlos syndrome before. We present a case with Ehlers–Danlos syndrome and multiple dermatofibromas. Case presentation: An 18-year-old Iranian woman presented with multiple purple nodules ranging from 0.5 to 1.5 cm in diameter, which were mobile and located on the proximal part of the lower limb. The dimple sign of these lesions was positive. During the physical examination, several features suggestive of Ehlers–Danlos syndrome were observed, including hyperextensibility and fragility of the skin, wide atrophic scars on the upper limb, hypermobility of joints and fingers, swan neck deformities of the digits, nodules on the knee, and striae alba on the leg. The patient was previously unaware of having Ehlers–Danlos syndrome. She had a history of asthma and atopic dermatitis. Family history was negative. A biopsy of the nodular lesions was performed, and the findings confirmed the diagnosis of dermatofibromas. Conclusion: We describe a patient with Ehlers–Danlos Syndrome who presented with multiple dermatofibromas. To our knowledge, this combination of findings is a previously unreported occurrence. [ABSTRACT FROM AUTHOR]

Emotional feelings are putatively ascribed to central representation of bodily states in the context of expectation and uncertainty in both internal state and external world. Neurodivergent people are more likely to experience co-occurring mental health challenges, although mechanistic insights underpinning this association are scarce. We therefore undertook a study to test whether imprecise processing of proprioceptive error signals may underlie the connection between neurodivergence and emotional dysregulation. In a cohort of people with complex chronic conditions, including chronic pain/fatigue, and complex trauma, and in a comparison group, we assessed presence of neurodivergence, variant connective tissue manifested through joint hypermobility, and emotional dysregulation. We present a data-informed conceptual model showing that variant connective tissue determines whether proprioceptive surprise is linked with emotional dysregulation in neurodivergent individuals. We suggest that future research in this area may have important clinical implications for the interaction of mental and physical wellbeing in neurodivergent people. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'. [ABSTRACT FROM AUTHOR]

Background: Ehlers–Danlos syndrome (EDS) is a rare inherited connective tissue disease characterized by hyperextensibility of the skin and joints and tissue fragility of the skin and blood vessels, Vascular EDS is the most severe form of EDS, with abnormal arterial fragility. There have been no reports of breast cancer occurring in patients with vascular EDS. Here, we report here a very rare case of breast cancer in a patient with vascular EDS. Case presentation: A 46-year-old woman with vascular EDS underwent partial left mastectomy and sentinel lymph node biopsy for left breast cancer (cStage 0) detected by medical examination. The final pathological diagnosis was invasive ductal carcinoma of the breast (pStage IA) [hormone receptor-positive, HER2 score 2 equivocal (FISH-positive), Ki-67LI 18%, luminal-HER2 type]. BluePrint was submitted as an aid in determining the postoperative treatment strategy, BluePrint Molecular Subtype HER2-type. However, the 10-year breast cancer mortality risk using Predict was low (5%). After consultation with the patient, the decision was made to administer postoperative radiation to the preserved breast along with hormone therapy only. There was no delay in postoperative wound healing, and the patient was free of metastatic recurrence for 9 months after surgery. Conclusion: We performed surgery, postoperative radiotherapy, and hormonal therapy in a breast cancer patient with vascular EDS without major complications. [ABSTRACT FROM AUTHOR]

Canine hip dysplasia (CHD) is a common orthopedic condition, influenced by both genetic and environmental factors. While current breeding programs often rely on ventrodorsal hip-extended (VDHE) radiographs, it is known they fail to accurately assess hip joint laxity. Therefore additional laxity-oriented diagnostic techniques have been developed. This study aims to evaluate the effectiveness of the Vezzoni modified Bädertscher distension device (VMBDD) technique, which quantifies hip joint laxity with the laxity index (LI), as a screening tool in two breeding programs. Data from a Belgian population of assistance dogs (population A) and a French population of guide dogs (population B) were analyzed. The heritability estimates of the LI, estimated using Bayesian statistical methods, were high in both populations (0.83 in population A and 0.82 in population B). Improved screening of parents by combining the VMBDD technique with the VDHE, significantly decreased LI and the prevalence of CHD in their offspring. In population A, when two parents were screened with the VMBDD compared to one, there was an average LI decrease of 0.03 (P<0.05). In population B, when one or both parents were screened with the VMBDD compared to none, the average LI decrease was 0.04 (P< 0.05) and 0.05 (P<0.01), respectively. In population A, screening both parents with the VMBDD in addition to the VDHE, resulted in 82.7% (P< 0.05) lower odds of CHD compared to screening only one parent. In population B, screening one parent led to 72.3% (P<0.05) lower odds of CHD compared to none of the parents being screened. In population B, when both parents were screened with the VMBDD, not a single case of CHD was observed in the puppies. In conclusion, based on these results, the VMBDD technique has the potential to drastically reduce CHD prevalence and is as such an excellent tool for breeding programs. [ABSTRACT FROM AUTHOR]

Vascular Ehlers–Danlos syndrome or Ehlers–Danlos syndrome type IV (vEDS) is a connective tissue disorder characterised by skin hyperextensibility, joint hypermobility and fatal vascular rupture caused by COL3A1 mutations that affect collagen III expression, homo-trimer assembly and secretion. Along with collagens I, II, V and XI, collagen III plays an important role in the extracellular matrix, particularly in the inner organs. To date, only symptomatic treatment for vEDS patients is available. Fibroblasts derived from vEDS patients carrying dominant negative and/or haploinsufficiency mutations in COL3A1 deposit reduced collagen III in the extracellular matrix. This study explored the potential of an antisense oligonucleotide (ASO)-mediated splice modulating strategy to bypass disease-causing COL3A1 mutations reported in the in-frame exons 10 and 15. Antisense oligonucleotides designed to redirect COL3A1 pre-mRNA processing and excise exons 10 or 15 were transfected into dermal fibroblasts derived from vEDS patients and a healthy control subject. Efficient exon 10 or 15 excision from the mature COL3A1 mRNA was achieved and intracellular collagen III expression was increased after treatment with ASOs; however, collagen III deposition into the extracellular matrix was reduced in patient cells. The region encoded by exon 10 includes a glycosylation site, and exon 15 encodes hydroxyproline and hydroxylysine-containing triplet repeats, predicted to be crucial for collagen III assembly. These results emphasize the importance of post-translational modification for collagen III homo-trimer assembly. In conclusion, while efficient skipping of target COL3A1 exons was achieved, the induced collagen III isoforms generated showed defects in extracellular matrix formation. While therapeutic ASO-mediated exon skipping is not indicated for the patients in this study, the observations are restricted to exons 10 and 15 and may not be applicable to other collagen III in-frame exons. [ABSTRACT FROM AUTHOR]

We report an index patient with complete insensitivity to pain and a history of painless fractures, joint hypermobility, and behavioral problems. The index patient descends froma familywith notable cases among hismaternal relatives, including his aunt and his mother's first cousin, both of whom suffer from congenital insensitivity to pain. The patient had normal results for prior genetic testing: fragile-X syndrome testing, chromosomal microarray analysis, and exome sequencing. Optical genome mapping detected a homozygous deletion affecting the noncoding 5' untranslated region (UTR) and the first non-coding exon of the SCN9A gene in all affected family members, compatiblewith recessive disease transmission. Pathogenic homozygous loss-of-function variants in the SCN9A gene are associated with impaired pain sensation in humans. Optical genome mapping can thus detect pathogenic structural variants in patients without molecular etiology by standard diagnostic procedures and is a more accessible diagnostic tool than short-read or long-read whole-genome sequencing. [ABSTRACT FROM AUTHOR]

Purpose Materials and Methods Results Conclusion Level of Evidence Robotic‐assisted technology in medial unicompartmental knee arthroplasty (mUKA) allows for customized adjustments of joint laxity through virtual preoperative component positioning before bone preparation. Nevertheless, the optimal balancing curve has yet to be delineated. This study sought to investigate if varying intraoperative knee laxity patterns had any impact on postoperative patient outcomes.A retrospective analysis was conducted on prospectively collected data from 326 fixed‐bearing RAUKA procedures performed between 2018 and 2022 with a minimum 2‐year follow‐up. Patients were categorized into three cohorts based on intraoperative joint laxity patterns (millimetres of joint gap during valgus stress) imparted at 20°, 60°, 90° and 120° of knee flexion: cohort 1 < +0.5 mm (tight); cohort 2 between 0.6 and 1.9 mm (physiologic); cohort 3 > 2 mm (loose). Wilcoxon and Kruskal–Wallis tests were conducted to assess patient‐reported outcome measure (PROM) improvements and preoperative and postoperative differences across the cohorts. A Spearman's test evaluated the correlation between knee balance at all degrees of flexion and preoperative and postoperative HKA.No differences in preoperative and postoperative PROMs were identified across the cohorts (p > 0.05). All three cohorts with different joint laxity patterns showed a significant improvement in the postoperative PROMS (p < 0.05). The preoperative or postoperative limb alignment did not significantly affect clinical outcomes relative to different laxity patterns.No differences were found in the outcomes across different joint laxity patterns in robotic‐assisted medial UKA using fixed‐bearing mUKAs. There was no evident advantage for maintaining a closer to physiologic laxity compared to tighter or looser balancing.Level III therapeutic study. [ABSTRACT FROM AUTHOR]

Background: Acute knee injuries represent a prevalent cause of morbidity among athletes and, if overlooked, could potentially lead to the development of chronic functional limitations. This study aimed to identify marrow contusion patterns around the knee and find the relation between each pattern and the intra- and extra-articular soft tissue injuries. This was a retrospective cross-sectional study carried out on 109 patients who presented to the hospital where the study was held with recent knee joint injury, for which magnetic resonance imaging was requested from January 2017 to January 2019. Results: The entire patient population under investigation had a mean age of 30.2 ± 9.7 years. Regarding gender distribution, the study comprised 90 males (82.6%) and 19 females (17.4%). Regarding bone marrow contusion patterns in all studied patients, it was pivot shift in 58 patients (53.2%), clip injury in 11 patients (10.1%), dashboard injury in 7 patients (6.4%), hyperextension injury in 3 patients (2.8%), lateral patellar dislocation in 15 patients (13.8%), and others in 15 patients (13.8%). In the pivot shift pattern group, anterior cruciate ligament (ACL), medial meniscus, and medial collateral ligament (MCL) injuries were most commonly seen in 94.8, 50, and 44.8% of patients, respectively. Among the clip pattern group, MCL, ACL, and medial meniscus injuries were most common in 90.9, 36.4, and 36.4%, respectively. Regarding the dashboard injury group, posterior cruciate ligament (PCL), ACL, and medial and lateral menisci were the most common injury structures (100, 57.1, 42.9, and 42.9%, respectively). Despite the hyperextension pattern being found in a small number of patients, it shows 100% medial meniscal and 66.7% PCL injuries. Within the group of lateral patellar dislocation patterns, 100% of cases exhibited injuries to the medial patellofemoral ligament. Conclusions: Precise localization of the marrow contusion around the knee and defining its pattern help to anticipate the most probable associated soft tissue injuries and, thus, can increase our sensitivity in their detection. This can have a better impact on patients' management outcomes. [ABSTRACT FROM AUTHOR]

Background: Total joint arthroplasty (TJA) is an orthopedic procedure commonly used to treat damaged joints. Despite the efficacy of TJA, postoperative complications, including aseptic prosthesis loosening and infections, are common. Moreover, the effects of individual genetic susceptibility and modifiable risk factors on these complications are unclear. This study analyzed these effects to enhance patient prognosis and postoperative management. Methods: We conducted an extensive genome-wide association study (GWAS) and Mendelian randomization (MR) study using UK Biobank data. The cohort included 2964 patients with mechanical complications post-TJA, 957 with periprosthetic joint infection (PJI), and a control group of 398,708 individuals. Genetic loci associated with postoperative complications were identified by a GWAS analysis, and the causal relationships of 11 modifiable risk factors with complications were assessed using MR. Results: The GWAS analysis identified nine loci associated with post-TJA complications. Two loci near the PPP1R3B and RBM26 genes were significantly linked to mechanical complications and PJI, respectively. The MR analysis demonstrated that body mass index was positively associated with the risk of mechanical complications (odds ratio [OR]: 1.42; p < 0.001). Higher educational attainment was associated with a decreased risk of mechanical complications (OR: 0.55; p < 0.001) and PJI (OR: 0.43; p = 0.001). Type 2 diabetes was suggestively associated with mechanical complications (OR, 1.18, p = 0.02), and hypertension was suggestively associated with PJI (OR, 1.41, p = 0.008). Other lifestyle factors, including smoking and alcohol consumption, were not causally related to postoperative complications. Conclusions: The genetic loci near PPP1R3B and RBM26 influenced the risk of post-TJA mechanical complications and infections, respectively. The effects of genetic and modifiable risk factors, including body mass index and educational attainment, underscore the need to perform personalized preoperative assessments and the postoperative management of surgical patients. These results indicate that integrating genetic screening and lifestyle interventions into patient care can improve the outcomes of TJA and patient quality of life. [ABSTRACT FROM AUTHOR]

Current international consensus of the appropriate Beighton score cut-off to define if a child has generalised joint hypermobile or not is based upon expert opinion. Our aim was to determine the prevalence of Beighton scores of children worldwide to provide a recommendation for establishing the Beighton score cut-off to identify generalised joint hypermobility in children. We used AMED, OVID Medline, Embase and CINAHL to find published articles from inception to April 2024 describing Beighton scores of children up to and including 18 years from the general population. We extracted study demographics including country of publication, total number of participants, summary data about the age and sex of participant, Beighton scores and any cut-off used where authors deemed children hypermobile and how many children were rated at the corresponding Beighton scores. There were 37 articles reporting on the prevalence or incidence of hypermobility at cut-off scores from 28,868 participants. Using the cut-off of ≥ 6 resulted in a prevalence of 6% for studies reporting male data and 13% for studies reporting female data. Limited data reporting availability precluded further sub-analysis at a Beighton score of ≥ 7, age, pubertal status and ethnicity. Conclusion: The working threshold for identifying generalised joint hypermobility in children should be a Beighton score of 6 or more. Our analysis also suggests a Beighton score of 7 or greater may be appropriate in childhood, particularly for females. What is Known: • The working threshold for identifying generalised joint hypermobility in children previously was set based on expert opinion. What is New: • The threshold to identify hypermobility in children should be at a minimum of ≥ 6 on the Beighton score. [ABSTRACT FROM AUTHOR]

An increasing number of reports suggest an association between a newly recognized disease cluster and significant and often disabling gastrointestinal (GI) symptoms. This cluster is composed of diagnoses of hypermobility spectrum disorders (HSDs) such as joint hypermobility and hypermobile variant Ehlers-Danlos syndrome (hEDS), postural orthostatic tachycardia syndrome (POTS), and mast cell activation syndrome (MCAS). The diagnosis of these entities remains a challenge, as the pathophysiology of each has not been completely elucidated and the diagnostic criteria continue to evolve. This article describes a cohort of young adult females who shared similar GI symptoms, with intractable nausea and vomiting being most prominent and gastroesophageal reflux disease and constipation also occurring. Most strikingly, these females also exhibited or reported a history of HSD, hEDS, POTS, and/or MCAS. The clinical course of their GI symptoms was remarkable for considerable challenges in management, and artificial nutritional support proved necessary for some. This article describes the clinical features and outcomes of their GI manifestations, examines how these manifestations might be linked to their systemic syndromes, and discusses whether a shared pathophysiology exists. Pending the definition of a common thread between these conditions, this article seeks to raise awareness of their clinical definitions and foster research that will hopefully improve outcomes for these patients. [ABSTRACT FROM AUTHOR]

Rabbits are mainly bred for human consumption and medical research. However, it has been recently showed that several rabbit breeds are also kept as pets for human leisure. The Netherlands dwarf rabbit is currently in the immense interest of many Vietnamese customers due to its personality and miniature stature. However, 12.1 kb deletion from position 44,709,089 to 44,721,236 bp in the high mobility AT‐hook 2 (HMGA2) gene on chromosome 4 was identified as the structural variant causing dwarfism and altered craniofacial development in this breed. It has been documented that HMGA2 plays an important role in regulating growth and individuals with genotype HMGA2 del/del are fatal several days after birth. Despite the economically high value of the Netherlands dwarf rabbit, there has been no study on the genetic survey of lethal alleles in this breed in Vietnam. The aim of this study is to develop a fast and reliable method to screen the frequency of lethal alleles of HMGA2 in the South of Vietnam. Rabbit saliva was collected, and DNA extraction was followed. Multiplex polymerase chain reaction (PCR) with three primers was optimized and performed to detect the presence of 12.1 kb deletion within the HMGA2 sequence. Our data showed that the 12.1 kb deletion in the Netherlands dwarf rabbit population was detected by our optimized multiplex PCR. In 100 rabbit animals, 34 and 16 individuals were homozygous wild type (+/+) and homozygous mutant (del/del), respectively, while 50 rabbits were heterozygous. The frequency of HMGA2 lethal allele carrier was 66% (66/100 individuals). Our results indicated that we successfully developed a fast, accurate multiplex PCR to detect carrier individuals. Verification of the genotypes was followed by sequencing. We recommend implementing our multiplex PCR procedure in genetic selection for carrier and homozygous wild‐type animals in the mating scheme to prevent the lethality of the rabbit offspring. Additionally, awareness should be raised among rabbit breeders to monitor the genetic makeup of the Netherlands dwarf rabbit populations. However, due to the limitation of the sample size, more samples should be taken in future studies to obtain the genetic frequency of the HMGA2 lethal allele more accurately. [ABSTRACT FROM AUTHOR]

Introduction: Ehlers-Danlos syndromes (EDS) is an umbrella term for a group of hereditary connective tissue disorders usually featuring hyperextensible skin, easy bruising, poor healing, and joint hypermobility. According to international Ehlers-Danlos support groups, the average time to diagnosis of this rare genetic condition is 10–12 years. Consequently, the journey to diagnosis can potentially be traumatic. This pilot study aims to explore female patients' journey to a diagnosis of EDS while living in Australia. Materials and methods: Over six weeks, from January to February 2023, a survey was distributed on EDS social media platforms including Facebook and LinkedIn. Ethical approval was obtained through the Ulster University Institute of Nursing and Health Research Ethics Filter Committee (FCNUR). Thematic and statistical analysis of the anonymous data was completed during March 2023. Results: 152 women completed the survey. More than half of the respondents first noticed symptoms of EDS more than 15 years prior to diagnosis and more than three quarters of respondents received other diagnoses prior to their EDS diagnosis. Most respondents saw their general practitioner, a physiotherapist and/or a rheumatologist prior to being correctly diagnosed with the condition. While some respondents had positive experiences with these health professionals, many felt that they were not listened to and, after doing their own research, had to educate their health professional/s about EDS. Conclusion: This pilot survey demonstrated that the journey to diagnosis of EDS for women in Australia is frequently long and traumatic. Participants indicated that more EDS education and training is needed for health professionals, especially GPs, to improve the diagnostic process. Implications for practice: Participants called for their self-reported symptoms to be listened to by health professionals and to be met with empathy and an open mind instead of being dismissed. Additional education and training to health professionals about connective tissue disorders including EDS may aid earlier diagnosis in Australia. [ABSTRACT FROM AUTHOR]

Background: For children with Osteogenesis Imperfecta (OI), a rare genetic bone disease, walking can be difficult to carry out due to a combination of bone fragility and deformity, muscle weakness, joint hypermobility, and pain. Bisphosphonate treatment has facilitated more children being able to walk, but for many, foot and ankle hypermobility is a limiting factor. Current evidence on foot orthoses in children with OI is sparse. This study aimed to evaluate gait characteristics in children with OI walking barefoot as compared to walking with foot orthoses. Methods: Twenty-three children with OI and hypermobility (mean age 8.3 ± 3.0 years) were included in this cross-sectional study. Children conducted three-dimensional gait analysis barefoot, and with foot orthoses and appropriate foot wear (stable yet light-weight), respectively. Walking speed, step length, lower limb kinematics and kinetics were collected. Differences in gait characteristics between test conditions were evaluated using paired sample t-tests. Results: When walking with foot orthoses, the external foot progression angle was reduced, peak ankle dorsiflexion angle increased, and peak plantarflexion moment increased as compared to barefoot. No difference was found in walking speed between test conditions, however, children with OI walked with longer steps with foot orthoses as compared to barefoot. Conclusion: The observed gait alterations suggest that foot orthoses, aiming to support the foot and ankle joint, contributed to reduced overall foot rotation as measured by external foot progression, increased peak plantarflexion moment, and increased step length. In a wider perspective, the ability to walk provides the opportunity to be physically active, and thereby increase skeletal loading and prevent fractures, thus, foot orthoses may be an important treatment option to consider in children with OI. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Simple Summary: This case report highlights two wild juvenile American black bears that were admitted to a rehabilitation facility but were euthanized due to severe immobility and joint laxity. Known musculoskeletal diseases of young bears are usually caused by trauma in the wild, or potentially rickets (a form of malnutrition) if raised in captivity. However, Case 1 was diagnosed with abnormal cartilage development (chondrodysplasia), likely of genetic origin, and Case 2 had osteoporosis and unidentified collagen abnormalities which are both unique to the current literature. With growing black bear populations, and increasing wildlife–human interface, we advise wildlife biologists and veterinarians to monitor and evaluate similar cases to help us further understand these uncommon diseases. Severe musculoskeletal disease characterized by marked joint laxity was the cause of euthanasia in two wild juvenile American black bears (Ursus americanus) admitted to a rehabilitation facility in eastern Tennessee in 2023. Previously, almost all reported musculoskeletal diseases in this population were of traumatic etiology, even in malnourished yearlings. Case 1 was an orphaned 11-month-old male cub exhibiting disproportionate dwarfism, progressive immobility, and joint laxity. Necropsy findings suggested either chondrodysplasia or rickets, and imaging findings supported a skeletal dysplasia. Case 2 was a 14-month-old emaciated male yearling exhibiting joint laxity and immobility. Necropsy findings showed osteoporosis and serous atrophy of fat, and imaging findings were inconsistent with a skeletal dysplasia. Both cases were clinically inconsistent with rickets based on normal calcium, phosphorous, and parathyroid hormone concentrations; however, Case 1 had hypovitaminosis D (9 nmol/L) compared to healthy juvenile black bears. We hypothesize that Case 1 had a genetic chondrodysplasia while the osteoporosis of Case 2 was due to chronic malnutrition. The goal of this case report is to inform wildlife agencies and facilities to monitor for similar, non-trauma-related debilitating musculoskeletal disease in free-ranging bears and evaluate cases that allow us to further understand the disease processes involved. [ABSTRACT FROM AUTHOR]

It is not entirely clear how the interaction between joint inflammation and the central nervous system (CNS) response in rheumatoid arthritis (RA) works, and what pathophysiology underlies the sex differences in coexisting neuropsychiatric comorbidities. It is known that estrogen hormones reduce inflammation in RA and that this occurs mainly via the stimulation of G protein-coupled receptor-30 (GPR30), also known as G protein-coupled estrogen receptor (GPER) 1. However, changes in GPR30 expression and sex differences induced by local and systemic inflammation in RA are not yet known. Our aim was to reveal sex differences in the expression and association of joint GPR30 with local and systemic inflammation, clinical course and furthermore with hippocampal GPR30 expression during pristane-induced arthritis (PIA) in Dark Agouti (DA) rats, an animal model of RA. Furthermore, we demonstrated sex-specific differences in the association between joint and systemic inflammation and hippocampal microglia during PIA. Our results suggest sex-specific differences not only in the clinical course and serum levels of pro-inflammatory cytokines but also in the expression of GPR30. Female rats show greater synovial inflammation and greater damage to the articular cartilage compared to males during PIA attack. Male rats express higher levels of synovial and cartilaginous GPR30 than females during PIA, which correlates with a less severe clinical course. The correlation between synovial and cartilaginous GPR30 and joint inflammation scores (Krenn and Mankin) in male rats suggests that the more severe the joint inflammation, the higher the GPR30 expression. At the same time, there is no particular upregulation of hippocampal GPR30 in males. On the other hand, female rats express higher levels of neuroprotective GPR30 in the hippocampus than male rats at the basic level and during PIA attack. In addition, females have a higher number of Iba-1+ cells in the hippocampus during PIA attack that strongly correlates with the clinical score, serum levels of IL-17A, and Krenn and Mankin scores. These results suggest that male rats are better protected from inflammation in the joints and female rats are better protected from the inflammation in the hippocampus during a PIA attack, independently of microglia proliferation. However, in the remission phase, synovial GPR30 expression suddenly increases in female rats, as does hippocampal GPR30 expression in males. Further experiments with a longer remission period are needed to investigate the molecular background of these sex differences, as well as microglia phenotype profiling. [ABSTRACT FROM AUTHOR]

Leucine zipper-like transcription regulator 1 (LZTR1) acts as a negative factor that suppresses RAS function and MAPK signaling; mutations in this protein may dysregulate RAS ubiquitination and lead to impaired degradation of RAS superfamily proteins. Germline LZTR1 variants are reported in Noonan syndrome, either autosomal dominant or autosomal recessive, and in susceptibility to schwannomatosis. This article explores the genetic and phenotypic diversity of the autosomal dominant LZTR1-related disorders, compiling a cohort of previously published patients (51 with the Noonan phenotype and 123 with schwannomatosis) and presenting two additional adult-onset cases: a male with schwannomatosis and Parkinson's disease and a female with Noonan syndrome, generalized joint hypermobility, and breast cancer. This review confirms that autosomal dominant LZTR1-related disorders exhibit an extreme phenotypic variability, ranging from relatively mild manifestations to severe and multi-systemic involvement, and offers updated frequences of each clinical feature. The aim is to precisely define the clinical spectrum of LZTR1-related diseases, using also two new emblematic clinical cases. Gaining insight into the mechanisms underneath this variability is crucial to achieve precision diagnostics and the development of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Volar plate injuries of the proximal interphalangeal (PIP) finger joint are common. Conservative treatment involves orthoses to limit hyperextension at the PIP joint yet allow movement of the joints to prevent joint stiffness and deformity. Custom-made dorsal blocking orthoses are recommended treatments. Previous research also supports the use of a figure-of-8 orthosis, although the comparative effectiveness of these orthoses is not currently known. This study aimed to compare the figure-of-8 orthosis and dorsal blocking orthosis for changes in the range of movement, pain, and function following stable volar plate PIP joint injuries and to compare the number of hand therapy appointments required. A parallel-group pilot randomized controlled trial. This trial was registered with the Australian and New Zealand Clinical Trials Registry (Trial ID: CTRN12619000449134). Participants aged 13-65 years were recruited from an outpatient hand therapy service and randomly assigned to experimental or control groups. The experimental group of 20 participants received a custom-made thermoplastic figure-of-8 orthosis limiting the extension to 15-20 degrees. The control group of 22 participants had a dorsal blocking orthosis, which was serially extended by 10 degrees weekly starting at 30 degrees flexion. Participants were blinded to their group allocation. Outcome measures included range of movement, edema, pain, function, and number of hand therapy appointments. Data collection was completed by the treating therapist who was not blinded to group assignment. Data analysis included a series of mixed-model analyses of variance to examine changes over time. Forty-two participants were recruited and had their data analyzed. No significant between-group differences were observed for DIP flexion, PIP flexion, pain, and function from baseline to follow-up. Both groups exhibited significant improvements in these outcomes over time (p < 0.001); effect sizes ranged from small to large (0.28-0.79). On average, the intervention group required 4 (±1.5) appointments compared to 6 (±1.5) in the control group over the same period representing a significant difference (p < 0.001). Both dorsal blocking and figure-of-8 orthoses provide similar outcomes. The use of a figure-of-8 orthosis, or a dorsal block orthosis fabricated in maximal comfortable extension depending on severity, could reduce the number of appointments and increase convenience for patients. • Dorsal blocking and figure-of-8 orthoses are effective for volar plate injuries. • Improvements in movement, edema, pain, and function were observed in both groups. • Figure-of-8 orthosis, or a dorsal block orthosis fabricated in maximal comfortable extension, could reduce the number of appointments. [ABSTRACT FROM AUTHOR]

Purpose: One of the most common types of coronal plane alignment of the knee (CPAK) is type I, which is characterised by varus alignment and apex distal joint line obliquity. The purpose of this study was to evaluate the association of changes in arithmetic hip–knee–ankle angle (aHKA) with both postoperative joint laxity and patient‐reported outcome measures (PROMs) in patients with CPAK type I following mechanical alignment (MA) total knee arthroplasty (TKA). Methods: Of 111 consecutive knees in 92 patients with osteoarthritis who underwent primary TKA, 80 knees (72.0%) with CPAK type I phenotype preoperatively were evaluated. All TKAs were performed to achieve neutral MA by a medial stabilising gap balancing technique. Pre‐ to postoperative change in aHKA was defined as ΔaHKA. The 80 CPAK type I knees were divided into a larger ΔaHKA group (>7°) and a smaller ΔaHKA group (≤7°). PROMs, including the Knee Society Score and Forgotten Joint Score‐12, were assessed before and 2 years after surgery. Pre‐ and postoperative joint laxity was assessed using a Telos arthrometer. Results: Twenty‐two knees showed a larger ΔaHKA, and postoperative lateral joint laxity in varus stress was significantly greater in these patients than in those with a smaller ΔaHKA (6.8° vs. 4.5°, p = 0.006). There were no significant differences between the groups in PROMs (p = n.s.). Conclusions: Postoperative lateral laxity was associated with larger aHKA changes than smaller aHKA changes in CPAK type I knees after TKA. However, no statistically significant differences in PROMs were found according to the amount of change in aHKA. Level of Evidence: Level III. [ABSTRACT FROM AUTHOR]

Introduction: 2p15p16.1 microdeletion syndrome was described for the first time in 2007. The size of the microdeletion is variable and encompasses several genes, like XPO1, USP34, BCL11A, REL, PAPOLG, PEX13, COMMD1, B3GNT2, and EHBP1. Features of the syndrome include short stature, microcephaly, hypotonia, psychomotor developmental delay, anomalies of the fingers of the upper and lower limbs, dysmorphic features like receding forehead, broad nasal bridge, telecanthus, ptosis, flat philtrum, small mouth with a high, narrow palate and everted lower lip. The precise genotype–phenotype correlation in 2p15 deletion syndrome is not understood. The aim of the study is to present the patient's medical history and the diagnostic process. Case Presentation: A boy aged 9 was admitted to the Genetic Outpatient Clinic due to dysmorphic features and mild mental retardation. Full lips, broad nasal root, very light hair, excessively developed subcutaneous tissue, joint laxity, postural defect, flat-valgus foot with sandal gap, brachydactyly, and problems with concentration, memory, and counting were found. Diagnosis was based on microarray testing, and copy-number variation analysis was performed using CytoScan 750K array. Genetic imbalance in the form of a deletion within the short arm of chromosome 2 in the 2p15 region (containing 50 kbp) was shown. The microdeletion covers 2 genes: USP34 and XPO1. Parents were not carriers of that mutation. Conclusion: The phenotypic features presented by the patient were reflected in the genetic test. 2p15 microdeletion syndrome is genetically heterogeneous with possible de novo occurrence, as in the presented case. The precise genotype–phenotype correlation in 2p15 deletion syndrome should be widely studied because in the literature there is mainly mentioned 2p15p16.1 syndrome. Even though 2p15 microdeletion syndrome is a rare discovery and its features are mainly mild, it is necessary to pay special attention to them to refer patients to genetic counseling to make an accurate diagnosis. [ABSTRACT FROM AUTHOR]

AbstractClinical onset and exacerbation of autosomal dominant SPG9A hereditary spastic paraplegia, including reversible wasting, has been described during pregnancy. SPG9A is due to ALDH18A1 mutations resulting in proline and ornithine deficiency. We present the case of a 29 year old primagravida at 32 weeks who presented with six months of upper limb amyotrophic wasting on a background unrecognized progressive spasticity due to SPG9A. The wasting reversed significantly following delivery. Our report highlights the unusual clinical features including cataract and joint laxity which may suggest SPG9A, echoes the existing descriptions of pregnancy-related provocation of amyotrophy in this condition and documents the outcome of two subsequent pregnancies following dietary intervention. [ABSTRACT FROM AUTHOR]

Background: Generalized Joint hypermobility (GJH) is predominantly non-symptomatic. In fact, individuals with joint flexibility usually perform better than their non-hypermobile counterparts during physical activities. Notwithstanding, strength and balance are essential to maintain the control of the extra range of motion during activities and to prevent musculoskeletal complications. There are limited and conflicting pieces of evidence in literature regarding the association between strength and balance in children with GJH. Objectives: The purpose of this study was to examine differences in functional strength, dynamic balance, proprioception, and isometric strength in children with and without joint hypermobility and determine the association between strength outcomes and dynamic balance. Method: A cross-sectional study was conducted among children aged 6 to 11. Hypermobility was determined using the Beighton Score, with scores ≥6 representing hypermobility. Functional strength was assessed with the Functional Strength Measure (FSM), isometric strength was determined with a handheld dynamometer (HHD), the Y-Balance Test (YBT) was used to assess dynamic balance and the Wedges test to measure proprioception. Results: This study included 588 participants (age: 7.97 ± 1.3 years; height: 128±10.1 cm; mass: 27.18 ± 7.98 kg). 402 children were classified as having normal mobility and 186 as being hypermobile. Hypermobile children had better functional strength in the lower extremities than children with normal range mobility but lower reach distance in the YBT. No differences in proprioception, functional strength of the upper extremity or isometric strength in the hands were found. However, isometric lower extremity force was less in hypermobile children than children with normal range mobility. Irrespective of their joint mobility, a fair significant correlation existed between total Y-balance distance and FSM items r = 0.16–0.37, p = 0.01. Correlations between total Y-balance distance and isometric strength of knee and ankle muscles ranged between r = 0.26–0.42, p = 0.001. Conclusion: Hypermobile joints seem to co-occur with lower extremity isometric strength, more functional strength in the lower extremities and less reaching distance in dynamic balance. The opposing direction of the results on functional and isometric strength tests highlights the importance of the type of outcome measures used to describe the association of strength and the range of motion. [ABSTRACT FROM AUTHOR]

Physical and cognitive decline at an older age is preceded by changes that accumulate over time until they become clinically evident difficulties. These changes, frequently overlooked by patients and health professionals, may respond better than fully established conditions to strategies designed to prevent disabilities and dependence in later life. The objective of this study was twofold; to provide further support for the need to screen for early functional changes in older adults and to look for an early association between decline in mobility and cognition. A cross-sectional cohort study was conducted on 95 active functionally independent community-dwelling older adults in Havana, Cuba. We measured their gait speed at the usual pace and the cognitive status using the MMSE. A value of 0.8 m/s was used as the cut-off point to decide whether they presented a decline in gait speed. A quantitative analysis of their EEG at rest was also performed to look for an associated subclinical decline in brain function. Results show that 70% of the sample had a gait speed deterioration (i.e., lower than 0.8 m/s), of which 80% also had an abnormal EEG frequency composition for their age. While there was no statistically significant difference in the MMSE score between participants with a gait speed above and below the selected cut-off, individuals with MMSE scores below 25 also had a gait speed<0.8 m/s and an abnormal EEG frequency composition. Our results provide further evidence of early decline in older adults–even if still independent and active—and point to the need for clinical pathways that incorporate screening and early intervention targeted at early deterioration to prolong the years of functional life in older age. [ABSTRACT FROM AUTHOR]

An objective of a total knee arthroplasty (TKA) is to restore native (i.e. healthy) function, and a crucial step is determining the correct insert thickness for each patient. If the insert is too thick, then stiffness results, and if too thin, then instability results. Two methods to determine the insert thickness are by manually assessing the joint laxity and by using a trial insert with goniometric markings that measures the internal-external rotation of the trial with respect to a mark on the femoral component. The former is qualitative and depends on the surgeon's experience and 'feel' and while the latter is quantitative, it can be used only with an insert with medial ball-in-socket conformity. An unexplored method is to measure the force required to push a trial insert into position. To determine whether this method has merit, the push force was measured in 30 patients undergoing unrestricted kinematically aligned TKA using an insert with ball-in-socket medial conformity, a flat lateral surface, and retention of the posterior cruciate ligament. During surgery, the surgeon determined three appropriate thicknesses to test from a selection ranging from 10 mm to 14 mm in 1 mm increments. The peak push forces going from an insert 1 mm thinner than the correct thickness as determined by an insert goniometer and from the correct thickness to 1 mm thicker were measured. Mean peak forces for the different insert thicknesses were 127 ± 104 N, 127 ± 95 N, and 144 ± 96 N for 1 mm thinner, correct, and 1 mm thicker, respectively, and did not differ (p = 0.3210). As a result, measurement of peak force during trial positioning of a tibial insert cannot be used to identify the correct thickness for all insert designs. [ABSTRACT FROM AUTHOR]

The biallelic variants of the POP1 gene are associated with the anauxetic dysplasia (AAD OMIM 607095), a rare skeletal dysplasia, characterized by prenatal rhizomelic shortening of limbs and generalized joint hypermobility. Affected individuals usually have normal neurodevelopmental milestones. Here we present three cases from the same family with likely pathogenic homozygous POP1 variant and a completely novel phenotype: a girl with global developmental delay and autism, microcephaly, peculiar dysmorphic features and multiple congenital anomalies. Two subsequent pregnancies were terminated due to multiple congenital malformations. Fetal DNA samples revealed the same homozygous variant in the POP1 gene. Expression of the RMRP was reduced in the proband compared with control and slightly reduced in both heterozygous parents, carriers for this variant. To our knowledge, this is the first report of this new phenotype, associated with a novel likely pathogenic variant in POP1. Our findings expand the phenotypic spectrum of POP1‐related disorders. [ABSTRACT FROM AUTHOR]