A skeleton in a huff: insights in etiologies of osteosclerosis.

A 30-yr-old man developed right lower leg pain and a palpable solid mass. Radiographic imaging revealed a periosteal reaction with an exostotic mass arising from the right distal fibula. Generalized skeletal osteosclerosis with periosteal reaction was discovered on a radiographic skeletal survey. A biopsy of the right fibular mass revealed reactive woven bone. The patient was referred to a metabolic bone disease clinic, where laboratory values were consistent with secondary hyperparathyroidism and increased bone turnover. A DXA bone density scan revealed high bone density, with an L1-4 spine Z-score of +9.3, a left femoral neck Z-score of +8.5, and a total hip Z-score of +6.5. A dental exam revealed generalized gingival inflammation, teeth mobility, generalized horizontal alveolar bone loss and widening of the periodontal ligament space, increased bone density around the teeth, and thickening of the radicular lamina dura. An extensive evaluation was performed, with the result of a single test revealing the diagnosis. The differential diagnoses of osteosclerosis affecting the skeleton, teeth, and oral cavity are discussed.

A 30-yr-old man developed, over a short period, pain in his lower right leg accompanied by a hard mass. He also reported weight loss and night sweats for the past 6 months. After evaluation by his primary physician, an X-ray was ordered that reported a bony mass arising from the right fibula bone. A biopsy was performed of the mass, but no evidence of cancer or any other specific abnormality was found. The patient was then referred to a bone disease specialty clinic. Laboratory tests revealed a large increase in how quickly the patient's skeleton was remodeling, affecting the balance of bone formation and removal involved in maintaining a healthy skeleton. A bone density scan reported that the patient had very dense bones. Other unusual changes were also discovered in a dental exam, suggesting bone thickening. After an extensive evaluation, a single blood test revealed the cause of the fibular bone mass and dense bones.

Comparison of Outcomes at Midterm Follow-up of Operatively and Nonoperatively Treated Isolated Weber B Ankle Fractures.

OBJECTIVES: A novel protocol was previously presented for nonoperative management of Weber B (OTA/AO 44B) ankle fractures with criteria of medial clear space <7 mm on gravity stress (GS) radiographs and ipsilateral superior clear space and contralateral GS medial clear space within 2 mm. This study recruited an operative cohort for comparison of outcomes. DESIGN: Retrospective cohort study. SETTING: Level 1 academic center. PATIENT SELECTION CRITERIA: The recruited operative cohort consisted of patients who may have been considered for the nonoperative protocol, but underwent surgery instead. OUTCOME MEASURES AND COMPARISONS: Kellgren-Lawrence scale for evaluation of arthritis, American Orthopedic Foot and Ankle Society Hindfoot, Olerud Molander Ankle, Lower Extremity Functional Scale (LEFS), and PROMIS (physical function, depression, pain interference) scores for the current operative cohort were compared with that of the original nonoperative cohort. RESULTS: There were 20 patients in the operative cohort and 29 in the original nonoperative cohort. Mean follow-up was 6.9 and 6.7 years, respectively. The following outcome scores were better for the nonoperative cohort compared with the operative, respectively: LEFS, 75.2 and 68.1 ( P = 0.009); Olerud Molander Ankle, 94.1 and 89.0 ( P = 0.05); American Orthopedic Foot and Ankle Society, 98.5 and 91.7 ( P = 0.0003); PROMIS Physical Function, 58.2 and 50.4 ( P = 0.01); PROMIS Pain Interference, 42.2 and 49.7 ( P = 0.004). The PROMIS Depression, 42.8 and 45.4 ( P = 0.29), was not different between groups. All patients achieved union of their fracture. Surgical complications included implant removal (15%), SPN neurapraxia (5%), and delayed wound healing (5%). CONCLUSIONS: In carefully selected patients with isolated Weber B fractures, nonoperative management may be considered because it can lead to equivalent or superior outcomes with none of the risks typically associated with surgical intervention. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Midterm Outcomes of Operatively and Nonoperatively Managed Achilles Tendon Ruptures in Young Adults.

Background: There continues to be controversy regarding treatment options for Achilles tendon ruptures (ATR). The aim of our study is to compare outcomes between operatively and nonoperatively managed Achilles ruptures in young adults (age 18-30 years), which has not been previously evaluated. Methods: At a single institution, all patients aged 18-30 years at time of injury who underwent treatment for an acute ATR from 2014 to 2021 were evaluated. Medical records were reviewed to collect demographics, dates of injury and treatment, smoking status, body mass index (BMI), Charlson Comorbidity Index (CCI), rate of deep venous thrombosis (DVT) after treatment, and rate of rerupture. Patients then completed Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) and pain interference (PI) questionnaires. Mann-Whitney nonparametric testing was used to evaluate for any statistical differences in PROMIS scores. Results: Sixty-six operative patients qualified and 28 (42%) participated. Thirty-seven nonoperative patients qualified and 14 (38%) participated. All patients had a CCI of 0. One patient in the operative cohort and 2 in the nonoperative reported active smoking. In the operative and nonoperative cohorts, respectively, the average age was 24.4 and 27.8 years; average BMI 26.5 (SD = 4.8) and 27.3 (SD = 4.3, P = .52); DVT rates 4 (6.1%) and 2 (5.4%); and rerupture rates 2 (3.0%) and 1 (2.7%), respectively. PROMIS scores did not differ in the operative and nonoperative groups: PROMIS PF mean of 60.4 (SD = 9.8) and 62.9 (SD = 9.1), respectively (P = .33); as well as PROMIS PI mean of 44.6 (SD = 5.9) and 43.9 (SD = 6.5), respectively (P = .59). Conclusion: This study should be interpreted with the understanding that we had a considerable loss to follow-up rate. In the study cohort, we found that young adults with ATR may be considered for either operative or nonoperative management. Rates of DVT, rates of rerupture, and PROMIS scores were not dissimilar between the 2 cohorts. Level of Evidence: Level III, retrospective cohort study.

Return to Sport After First Metatarsophalangeal Arthrodesis: A Systematic Review.

BACKGROUND: First metatarsophalangeal (MTP) arthrodesis is a common surgical intervention for addressing MTP pain and deformity. Despite great interest on the topic of return to sport (RTS) after first MTP arthrodesis in the literature, no systematic review exists on this topic. The purpose of this systematic review is to investigate RTS after first MTP arthrodesis. METHODS: This study is a systematic review using PubMed, Web of Science, CINAHL, and MEDLINE from database inception until May 10, 2023. Search algorithm used was (MTPJ OR MTP OR "hallux rigidus" OR cheilectomy OR metatarsal OR metatarsophalangeal) AND (arthrodesis OR fusion) AND sport. Inclusion criteria were surgical intervention of first MTP arthrodesis and outcomes related to sport. RESULTS: Ten articles were included out of 249 articles initially retrieved. Patients (n = 450) had a frequency weighted mean (FWM) age of 58.6 ± 5.1 years with a FWM follow-up time of 32.1 ± 18.9 months. A total of 153 patients (reported in 34.0% of patients) had a FWM postoperative Foot and Ankle Ability Measure Sport score of 70.4 ± 21.8 at final follow-up. For sporting activities reported by multiple studies (running, yoga, golf, hiking, tennis, elliptical, and biking), about 9.8% to 28.1% of patients (n = 69 reports) stated that sporting activity difficulty decreased, 67.2% to 87.5% of patients (n = 340 reports) stated that sporting activity remained the same, and 1.8% to 8.5% of patients (n = 23 reports) stated that sporting activity difficulty increased after first MTP arthrodesis depending on the sporting activity. One article reported RTS time of 11.7 ± 5.1 weeks after first MTP arthrodesis (n = 39). CONCLUSION: RTS after first MTP arthrodesis is highly variable depending on patient and sport. Numerous different sporting activities have high rates of RTS after first MTP arthrodesis, with a majority of patients reporting similar or increased ability to perform sporting activities after surgery.

Lateral Talar Subluxation Measurements in Nonoperatively Managed Weber B Ankle Fractures.

Background: Lateral talar subluxation (LTS) was introduced as a measurement tool for evaluating isolated Weber B ankle fractures, with LTS >4 mm on gravity stress (GS) radiographs possibly indicating need for surgery. This study reviews LTS measurements in nonoperatively managed isolated Weber B fibula fractures to further investigate the validity of this previously stated cutoff. Methods: The senior authors previously reported outcomes of a novel algorithm for nonoperative management of isolated Weber B ankle fractures. Outcome scores reported include American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot, Olerud-Molander (OMA), Foot and Ankle Ability Measure for activities of daily living (FAAM/ADL), and visual analog scale (VAS) scores. All patients achieved union of their fracture. LTS was measured on GS radiographs of both injured and contralateral uninjured extremities. Results: Forty-two patients were included with minimum 1-year follow-up. Average age was 49 years (range 19-72). Mean measurements on injury GS radiographs were as follows: medial clear space (MCS) 4.45 mm (SD = 0.93), superior clear space (SCS) 3.46 mm (SD = 0.70), and LTS 2.33 mm (SD = 1.57, range 0-4.7 mm), with 35 (83.3%) patients having injury LTS ≤4 mm. Mean measurements on contralateral (uninjured) GS radiographs were as follows: MCS 3.39 mm (SD = 0.63), SCS 3.15 mm (SD = 0.50), and LTS 1.30 mm (SD = 1.28, range 0-4.8 mm). There was no statistically significant difference in all outcome measures based on amount of LTS (<2 mm, 2-4 mm, >4 mm). Conclusion: Most patients had injury LTS ≤4 mm, although those with LTS >4 mm had excellent outcome scores. LTS measurements on normal ankles reveal a large range. LTS may be a useful adjunct in evaluating isolated Weber B ankle fractures but the 4-mm cutoff may not be entirely reliable. Further studies are required to validate LTS as a decision-making tool. Level of Evidence: Level IV, case series.

Cross-cultural Adaptation and Psychometric Evaluation of the Persian Version of the Satisfaction and Recovery Index (SRI): Structural Validity, Construct Validity, Internal Consistency, and Test-retest Reliability.

Background: The Satisfaction and Recovery Index (SRI) is a generic importance-weighted health satisfaction tool to measure the process and state of recovery following musculoskeletal injuries. The objectives of this study are (1) to translate and cross-culturally adapt the SRI to Persian and (2) evaluate its psychometric properties. Methods: The forward-backward translation technique was used for translation, and two rounds of cognitive interviews were conducted to assess cultural appropriateness. Participants (n=100, mean age=32.5, 82%male) had acute (i.e., <30 days) musculoskeletal injuries of any etiology. Structural validity, construct validity, internal consistency, and test-retest reliability were evaluated. Results: Participants identified issues in 3/6 areas of a coding system during the cognitive interviews: comprehension/clarity, relevance, and inadequate response definition. These issues informed subsequent changes to arrive at the final version of the SRI-P. The SRI-P had adequate construct validity (P<0.001), the confirmatory factor analysis demonstrated a two-factor structure, the internal consistency was acceptable (Cronbach's α=0.83), and it was deemed reliable (ICC2, 1=0.72). Conclusion: The psychometric evaluation revealed that the SRI-P has adequate construct validity, internal consistency, and test-retest reliability. Unlike the original English version, the SRI-P has a two-factor structure, which appears to be related to cultural differences in interpreting some of the items. The clinical importance of this study is that the SRI (which captures the state of recovery and how important the various items of the tool are to each patient and how satisfied they are with their recovery) can now be available to surgeons and therapists in the orthopedic and rehabilitation realms in Persian populations.

MYB insufficiency disrupts proteostasis in hematopoietic stem cells, leading to age-related neoplasia.

MYB plays a key role in gene regulation throughout the hematopoietic hierarchy and is critical for the maintenance of normal hematopoietic stem cells (HSC). Acquired genetic dysregulation of MYB is involved in the etiology of a number of leukemias, although inherited noncoding variants of the MYB gene are a susceptibility factor for many hematological conditions, including myeloproliferative neoplasms (MPN). The mechanisms that connect variations in MYB levels to disease predisposition, especially concerning age dependency in disease initiation, are completely unknown. Here, we describe a model of Myb insufficiency in mice that leads to MPN, myelodysplasia, and leukemia in later life, mirroring the age profile of equivalent human diseases. We show that this age dependency is intrinsic to HSC, involving a combination of an initial defective cellular state resulting from small effects on the expression of multiple genes and a progressive accumulation of further subtle changes. Similar to previous studies showing the importance of proteostasis in HSC maintenance, we observed altered proteasomal activity and elevated proliferation indicators, followed by elevated ribosome activity in young Myb-insufficient mice. We propose that these alterations combine to cause an imbalance in proteostasis, potentially creating a cellular milieu favoring disease initiation.

Mouse Phenome Database: towards a more FAIR-compliant and TRUST-worthy data repository and tool suite for phenotypes and genotypes.

The Mouse Phenome Database (MPD; https://phenome.jax.org; RRID:SCR_003212), supported by the US National Institutes of Health, is a Biomedical Data Repository listed in the Trans-NIH Biomedical Informatics Coordinating Committee registry. As an increasingly FAIR-compliant and TRUST-worthy data repository, MPD accepts phenotype and genotype data from mouse experiments and curates, organizes, integrates, archives, and distributes those data using community standards. Data are accompanied by rich metadata, including widely used ontologies and detailed protocols. Data are from all over the world and represent genetic, behavioral, morphological, and physiological disease-related characteristics in mice at baseline or those exposed to drugs or other treatments. MPD houses data from over 6000 strains and populations, representing many reproducible strain types and heterogenous populations such as the Diversity Outbred where each mouse is unique but can be genotyped throughout the genome. A suite of analysis tools is available to aggregate, visualize, and analyze these data within and across studies and populations in an increasingly traceable and reproducible manner. We have refined existing resources and developed new tools to continue to provide users with access to consistent, high-quality data that has translational relevance in a modernized infrastructure that enables interaction with a suite of bioinformatics analytic and data services.

Hammer Toe Correction with Proximal Interphalangeal Joint Arthrodesis.

Background: First described by Soule in 1910, arthrodesis of the proximal interphalangeal joint is a common operative method of treatment of hammer toe, or fixed-flexion deformity of the proximal interphalangeal joint of the lesser toes1. The deformity is often caused by imbalance in intrinsic and extrinsic muscle function across the interphalangeal joint and metatarsophalangeal joint2,3, which can be effectively addressed through proximal interphalangeal joint straightening and arthrodesis in conjunction with soft-tissue balancing of the metatarsophalangeal joint. Description: Following longitudinal skin incision over the joint, a transverse extensor tenotomy and capsulotomy reveal the proximal interphalangeal joint and provide appropriate exposure of the head of the proximal phalanx. With the soft tissues protected, the proximal and middle phalanges undergo resection of the articular surfaces to allow osseous apposition. This step can be performed with a rongeur sagittal saw or with osteotomes4,5. The head of the proximal phalanx is resected proximal to the head-neck junction, and the proximal portion of the middle phalanx is removed to expose the subchondral bone. Often, there is a dorsal contracture of the metatarsophalangeal joint that is elevating the toe, which is addressed with use of a longitudinal incision over the metatarsophalangeal joint, a Z-lengthening of the long extensor tendon to the toe, and a subsequent capsulectomy. If there is an angular component to the deformity, the collateral ligaments are released from the metatarsal neck, and the toe can be balanced. If there is residual subluxation of the joint that is incompletely corrected by soft-tissue procedures, a metatarsal osteotomy should be considered. Fixation is then performed with use of a smooth Kirschner wire. The wire is inserted from the middle phalanx out the tip of the toe and subsequently inserted retrograde across the proximal interphalangeal joint, often into the metatarsal head and neck, holding the metatarsophalangeal joint in appropriate position. This step can also be completed with use of novel methods including screws, bioabsorbable pins, or intramedullary implants6-8. Alternatives: Nonoperative treatments for hammer toe deformity are generally pursued prior to surgery and include shoe modifications such as a wide toe-box, soft uppers, and padding of osseous prominences3,9,10. Alternative surgical treatments include proximal interphalangeal arthroplasty, soft-tissue capsulotomy, extensor tendon lengthening, and amputation11. Rationale: Although nonoperative treatment can alleviate symptoms temporarily, surgical treatment is often necessary for definitive treatment of hammer toe. Soft-tissue procedures such as tendon lengthening can provide a stabilizing benefit, but the degenerative bone changes associated with hammer toe are better addressed with use of resection of the proximal interphalangeal joint3. Arthroplasty allows for some retained motion; however, this motion may lead to deformity and pain over time2. Arthrodesis provides less painful and more reliable fixation as well as equal outcomes compared with other operative techniques. Patient satisfaction rates after this procedure are high, with pain relief in up to 92% of patients and rare complications7-12. Expected Outcomes: Outcomes of this procedure are favorable, with rates of osseous fusion ranging from 83% to 98%2,4,11,13. Patient satisfaction rates range from 83% to 100%4,11. Historically, patients have expressed dissatisfaction with pain and the appearance of exposed hardware, but novel internal fixative devices provide a more natural appearance to the toe without the need for secondary surgical procedures for pin removal8,14. Patients are often able to return to regular activity at 6 weeks postoperatively; however, there may be persistent pain or swelling in the toe. Wide shoes and activity modifications are frequently continued for several more weeks postoperatively, and some patients may benefit from formal physical therapy and at-home rehabilitation. Important Tips: Avoid vascular compromise by ensuring adequate resection of bone at the proximal interphalangeal joint.A longitudinal incision across the joint provides greater exposure but can lead to scar contracture that elevates the toe. One alternative is the use of an elliptically shaped incision over the proximal interphalangeal joint, which can improve cosmesis but does restrict exposure.Excessive osseous resection can lead to a cosmetically undesirable short toe.If using an implant for the arthrodesis, ensure the implant is not too big for the toe. Most implants are too big for fifth-toe arthrodesis.In toes with severe deformity, fixation with a Kirschner wire is often preferred because excessive stretching of the neurovascular bundle can lead to toe compromise and if Kirschner wire is used the pin can easily be removed at bedside.For flexible deformities, a nonoperative approach is recommended, such as stretching exercises, shoe-wear modifications, and metatarsal pads. A tenotomy of the flexor digitorum brevis is a soft-tissue procedure that can be considered if nonoperative treatment is insufficient to correct the deformity. If flexor digitorum brevis tenotomy does not adequately treat proximal interphalangeal joint deformity, a proximal interphalangeal joint arthrodesis should be the next step. Acronyms and Abbreviations: MTP = metatarsophalangealPIP = proximal interphalangeal.

Recovery Trajectories Following Complex Elbow Injuries and Radial Head Arthroplasty: A Longitudinal Study Over 8 Years.

PURPOSE: Radial head arthroplasty (RHA) is commonly performed to manage comminuted unreconstructible radial head fractures. Although the outcomes of RHA are often satisfactory, revisions are usually considered when pain intensity is higher than expected. Therefore, it is important to investigate the recovery trajectories of patients following RHA over an extended period and the characteristics that may lead to unfavorable outcomes. METHODS: The Patient-Rated Elbow Evaluation (PREE) was used to assess recovery in 94 patients at baseline (within 2-7 days after surgery); 3 and 6 months; and 1, 2, 3, 4, 5, and 8 years after RHA. Lower PREE values indicate lower pain and disability. Latent growth curve analysis was used to determine classes of recovery. The characteristics of the participants in the identified recovery trajectory classes were then compared. RESULTS: Two distinct recovery trajectories were identified: optimal and suboptimal recoveries. Most patients (84%) belonged to the optimal recovery class, which exhibited significantly lower baseline PREE scores, a consistent pattern of recovery, and a relatively high rate of change. Patients in the suboptimal recovery class (16%) had significantly higher baseline PREE scores and continued to experience relatively higher levels of pain and disability for the duration of the study; their rate of recovery was much slower. Patients belonging to the 2 recovery trajectories did not differ based on age or sex. Although we had low power in other variables, a qualitative exploration showed that the number of current or previous smokers was higher in the suboptimal recovery trajectory class. CONCLUSIONS: In this longitudinal cohort study, we show that high postsurgical pain and disability, and potentially smoking, may adversely affect the recovery trajectory following RHA. Clinicians are recommended to assess these potential factors while considering revision surgeries. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

How Is the Probability of Reporting Various Levels of Pain 12 Months After Noncatastrophic Injuries Associated with the Level of Peritraumatic Distress?

BACKGROUND: Psychological factors have been shown to be consistent predictors of chronic pain in people with musculoskeletal injuries. However, few prognostic studies have considered multiple risk factors including peritraumatic distress. In addition, previous research has not considered that the associations between peritraumatic distress and pain levels can vary across pain outcomes. QUESTION/PURPOSE: To determine whether an easily measurable level of baseline distress is associated with pain levels 1 year after noncatastrophic traumatic injuries when the outcome to be assessed is not normally distributed. METHODS: This was a prospective cohort study. The data were captured from two cohorts in London, Ontario, Canada, and Chicago, IL, USA. Participants were adults with acute noncatastrophic (that is, not treated with surgery or hospitalization) musculoskeletal injuries of any etiology with various injury locations (60% [145 of 241] spinal and 40% [96 of 241] peripheral) that presented to local urgent care centers. Other inclusion criteria included English/French speakers and having no other disorder that would affect their pain levels. In total, between the years 2015 and 2018, 241 participants were recruited based on the inclusion criteria. Ninety-three percent (225 of 241) of participants provided baseline data, and of these, 48% (109 of 225) were lost to follow-up in 1 year. Based on a complete case approach, this study included 116 participants who ranged in age from 18 to 66 years and 69% (80) of whom were women. The Traumatic Injuries Distress Scale (TIDS) was used to evaluate distress at baseline (within 4 weeks of injury). The TIDS is a validated, reliable 12-item risk prognosis screening tool that takes less than 3 minutes to complete with questions regarding uncontrolled pain, negative affect, and intrusion/hyperarousal. The minimum and maximum possible scores are 0 and 24, with higher scores indicating higher levels of distress. The Numeric Pain Rating Scale (NPRS) was used to assess the pain level at baseline and again 12 months postinjury. To complete the NPRS, participants rate the severity of their pain on a scale of 0 to 10, with 0 indicating no pain and 10 indicating the worst pain imaginable. NPRS scores of 1 to 3 indicate mild pain, 4 to 6 indicate moderate pain and 7 or higher indicate severe pain. As a preliminary analysis, to assess whether the participants as a group experienced recovery, a paired samples t-test was used to compare NPRS scores at baseline and 12 months. In all, 52% (60 of 116) of participants reported no pain (NPRS = 0), and mean pain intensity scores improved from 4.8 ± 2.1 at baseline to 1.6 ± 1.6 at 12-month follow-up (p < 0.001). Quantile regression was used to describe the association between baseline distress and pain levels 1 year after the injury. This technique was used because it reveals the relationships at different quantiles of the pain outcome distribution. RESULTS: The results indicate some people (52% [60 of 116]) recovered regardless of their baseline level of distress (30th quantile of the NPRS: ß = 0). However, in those with persisting pain, higher levels of baseline distress are associated with greater levels of pain 12 months after the injury (50th quantile of the NPRS: ß = 0.11; p = 0.01; 70th quantile of the NPRS: ß = 0.27; p < 0.001; 90th quantile of the NPRS: ß = 0.31; p = 0.01). According to this model, with a baseline TIDS score of 5, there is 10% probability that patients will report moderate or greater levels of pain (4 or higher of 10) 12 months later. This probability then increases as the TIDS score increases. For instance, at a score of 13 on the TIDS, the probability of a patient reporting moderate or higher levels of pain increases to 30%, and the probability of reporting severe pain (higher than 6 of 10) is 10%. CONCLUSION: Clinicians and surgeons in orthopaedic settings can screen for the presence of peritraumatic distress using the TIDS, which is an easily administered tool that does not require extensive knowledge of psychology, and by using it they can identify those with higher levels of distress who are more likely to have persistent, long-term pain. A score of 4 or less indicates a low risk of persistent pain, a score between 5 and 12 (endpoints included) indicates moderate risk, and a score of 13 or higher indicates high risk. Future studies should investigate whether certain immediate interventions for peritraumatic distress in the aftermath of trauma can decrease the likelihood that a patient will develop chronic pain after injury. As an analysis technique, quantile regression is useful to assess complex associations in many orthopaedic settings in which a certain outcome is expected to occur in most patients leading to non-normally distributed data. LEVEL OF EVIDENCE: Level II, therapeutic study.

Infantile Aphakic Glaucoma: A Proposed Mechanism.

PURPOSE: To review information pertaining to secondary glaucoma following infant lensectomy and provide evidence to support the mechanism responsible for this condition. METHODS: Reported risk factors and proposed mechanisms for infantile aphakic glaucoma are reviewed. Laboratory studies and clinical observations in affected patients with glaucoma are described. Evidence of postoperative anterior chamber fibrosis is reviewed and interpreted. RESULTS: Clinical evidence demonstrated the development of anterior chamber fibrosis following infant cataract surgery. Laboratory studies showed liberated lens epithelial cell transition to fibroblasts. CONCLUSIONS: The review and assessment of laboratory and clinical evidence support the proposal that infantile aphakic glaucoma is caused, in part, by postoperative anterior chamber fibroization related to lens cell dispersion, cytokine activation, and epithelial-mesenchymal transition with resultant filtration angle fibrosis and secondary loss of filtration function. [J Pediatr Ophthalmol Strabismus. 2022;59(4):236-242.].

Glaucoma following Infant Lensectomy: 2021 Update.

PURPOSE: To review information pertaining to glaucoma following infant lensectomy surgery and to provide evidence to support the responsible mechanism of this condition. METHODS AND RESULTS: Described risk factors and proposed mechanisms for infantile aphakic glaucoma were assessed. The clinical evidence observed in affected glaucoma patients was analyzed, and evidence of postoperative anterior chamber fibrosis was reviewed and interpreted. CONCLUSION: The review and assessment of laboratory and clinical evidence support the proposal that infantile aphakic glaucoma is caused, in part, by postoperative anterior chamber fibroization related to lens cell dispersion and active epithelial-mesenchymal transition with resultant filtration angle tissue injury and loss of function.

An Exploration of Blood Marker×Environment Interaction Effects on Pain Severity and Interference Scores in People With Acute Musculoskeletal Trauma.

OBJECTIVES: Explore the moderating effects of psychological or social variables on associations between biomarkers of inflammation/stress and clinical reports of pain. METHODS: This is a cross-sectional exploratory study. Data were drawn from the Systematic Merging of Biology, Mental Health and Environment (SYMBIOME) longitudinal study (clinicaltrials.gov ID no. NCT02711085). Eligible participants were adults who presented to an Urgent Care Centre in Ontario, Canada within 3 weeks of a noncatastrophic musculoskeletal trauma (no surgery or hospitalization). A questionnaire package was given that included the Brief Pain Inventory (capturing pain severity and pain interference) and relevant person-level variables. Blood samples were also drawn for serum analysis of 8 target biomarkers (brain-derived neurotrophic factor, transforming growth factor beta 1 [TGF-ß1], c-reactive protein, tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, IL-10, and cortisol). RESULTS: Employment before trauma (employed for pay/not employed for pay) fully moderated the association between tumor necrosis factor-α and pain severity (∆R2=4.4%). Pre-existing psychopathology (yes/no) fully moderated the association between TGF-ß1 and pain severity (∆R2=8.0%). Sex (male/female) fully moderated the association between c-reactive protein and pain severity (∆R2=6.3%). A pre-existing pain condition (yes/no) was significantly associated with worse pain interference (R2=7.2%), and partially moderated the effect of IL-1ß on pain interference (∆R2=6.9%). Higher peritraumatic life stress significantly explained 8.9% of variance in pain interference alone, and partially moderated the effect of TGF-ß1 on interference (∆R2=4.4%). DISCUSSION: Simple bivariate associations between blood-based markers and clinical symptoms are unlikely to reveal meaningful relationships. However, when stratified by existing person-level or "metadata" variables, an association may exist for at least 1 clinically relevant subgroup.

Perioperative Management of Antirheumatic Medications in Patients with RA and SLE Undergoing Elective Foot and Ankle Surgery: A Critical Analysis Review.

¼: Recent literature has shown that continued use rather than discontinuation of various antirheumatic agents throughout the perioperative period may present an opportunity to mitigate the risks of elective surgery. ¼: For patients with rheumatoid arthritis and systemic lupus erythematosus, perioperative management of medication weighs the risk of infection against the risk of disease flare when immunosuppressive medications are withheld. ¼: Broadly speaking, current evidence, although limited in quality, supports perioperative continuation of disease-modifying antirheumatic drugs, whereas biologic drugs should be withheld perioperatively, based on the dosing interval of the specific drug. ¼: For any withheld biologic drug, it is generally safe to restart these medications approximately 2 weeks after surgery, once the wound shows evidence of healing, all sutures and staples have been removed, and there is no clinical evidence of infection. The focus of this recommendation applies to the optimization of wound-healing, not bone-healing. ¼: In most cases, the usual daily dose of glucocorticoids is administered in the perioperative period rather than administering "stress-dose steroids" on the day of surgery.

Latent profile analysis of blood marker phenotypes and their relationships with clinical pain and interference reports in people with acute musculoskeletal trauma.

Background: The prevalence of inadequate treatments for chronic pain has necessitated the search for biological factors that influence the transition to chronicity. Methods: Antecubital blood was drawn from those who experienced acute, noncatastrophic musculoskeletal trauma. Follow-up occurred at 1, 3, 6, and 12 months with the primary outcome being Brief Pain Inventory (BPI) Functional Interference scores. Eight markers were chosen for latent profile analysis: brain-derived neurotrophic factor (BDNF); transforming growth factor-beta 1 (TGF-ß1); C-reactive protein (CRP); tumor necrosis factor-alpha (TNF-α); interleukins (ILs) 1-beta, 6, and 10; and the stress hormone cortisol. Results: Mean age of the 106 participants was 44.6 years and 58.5% were female. The final model indicated a three-class solution that could be adequately described by three of the eight markers: class 1 = low concentration of all markers (33.9% of the sample), class 2 = average concentration of all markers (47.7%), and class 3 = high concentration of BDNF and TGF-ß1 (18.3%). BPI Pain Interference scores captured at both inception and 6-month follow-up were compared across the three groups. Mean scores were significantly higher in class 3 for the BPI Interference subscale at inception (27.0 [SD 16.4] vs. 35.8 [SD 17.3], P = 0.05) and at 6-month follow-up (2.2 [SD 4.8] vs. 7.3 [SD 10.7], P = 0.03) compared to those of the other two classes. Conclusions: Although recovered populations are not significantly different in BDNF and TGF-ß1 levels, those who experience persisting disability are more likely to have moderate to high levels in serum.

Contexte: La prévalence des traitements inadéquats pour la douleur chronique a nécessité la recherche des facteurs biologiques qui influencent le passage à la chronicité.Méthodes: Du sang du pli du coude a été prélevé sur des personnes ayant subi des traumatismes musculo-squelettiques aigus non invalidants. Le suivi a eu lieu à 1, 3, 6 et 12 mois avec les scores d'interférence fonctionnelle du Questionnaire concis de la douleur (QCD) comme résultat principal. Huit marqueurs ont été choisis pour l'analyse du profil latent : le facteur neurotrophique dérivé du cerveau (BDNF); le facteur de croissance transformant-bêta 1 (TGF-ß1); la protéine C-réactive (CRP); le facteur de nécrose tumorale alpha (TNF-a); les interleukines (IL) 1-bêta, 6 et 10; et le cortisol, l'hormone du stress.Résultats: L'âge moyen des 106 participants était de 44,6 ans et 58,5% étaient des femmes. Le modèle final a indiqué une solution à trois classes qui pourrait être correctement décrite par trois des huit marqueurs : classe 1 = faible concentration de tous les marqueurs (33,9 % de l'échantillon), classe 2 = concentration moyenne de tous les marqueurs (47,7 %), et classe 3 = concentration élevée de BDNF et TGF-ß1 (18,3 %). Les scores d'interférence de la douleur BPI relevés à la fois au début et au suivi à 6 mois ont été comparés entre les trois groupes. Les scores moyens étaient significativement plus élevés dans la classe 3 pour la sous-échelle d'interférence BPI au début (27,0 [SD 16,4] comparativement à 35,8 [SD 17,3], p = 0,05) et à 6 mois de suivi (2,2 [SD 4,8] comparativement à 7,3 [SD 10,7], P = 0,03) par rapport à ceux des deux autres classes.Conclusions: Bien que les populations rétablies ne soient pas significativement différentes en ce qui a trait aux niveaux de BDNF et de TGF-ß1, celles qui souffrent d'une incapacité persistante sont plus susceptibles d'avoir des taux sériques modérés à élevés.

Long-term Follow-up of Lisfranc Injuries Treated With Open Reduction Internal Fixation Patient-Reported Outcomes.

BACKGROUND: There remains a paucity of data regarding long-term patient-reported outcomes following Lisfranc injuries. We sought to collect long-term clinical outcome data following Lisfranc injuries using PROMIS Physical Function (PROMIS-PF) and visual analog scale-foot and ankle (VAS-FA). METHODS: A chart review was performed to identify all patients who had surgical treatment of an acute Lisfranc injury at our institution from 2005 to 2014. Of the 45 patients identified, we were able to recruit 19 for a follow-up clinic visit consisting of physical examination, administration of questionnaires addressing pain and medication usage, radiographs, and completion of outcome surveys including PROMIS-Physical Function and visual analog scale-foot and ankle. RESULTS: There were 14 female and 5 male patients enrolled in the study with a mean time of 6.25 years from the time of injury. Within this cohort, the mean PROMIS-PF score was 52.4±8.2 and the mean VAS-foot and ankle score was 76.6±22.3. CONCLUSION: We report satisfactory long-term patient-reported outcomes using PROMIS-PF and VAS-FA. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Failure of Goniosurgery for Glaucoma Associated With Sturge-Weber Syndrome.

PURPOSE: To report the surgical results of goniosurgery for children with glaucoma associated with Sturge-Weber syndrome. METHODS: Retrospective review of medical records of patients who had initial goniosurgery for glaucoma associated with Sturge-Weber syndrome. RESULTS: A total of 46 eyes of 42 patients who had glaucoma associated with Sturge-Weber syndrome and were treated with initial goniosurgery were identified to determine the efficacy of therapeutic goniotomy and trabeculotomy (goniosurgery). The average age at the time of goniosurgery was 1.5 years (range: 1 month to 23 years). Office intraocular pressure (IOP) measurements before goniosurgery were recorded in 76% of patients (32 of 42 patients) with an average measurement of 35 mm Hg (range: 25 to 50 mm Hg). The average interval to failure was 4 months (range: 1 to 48 months). Forty-six eyes underwent goniosurgery with a rate of failure of 98% (45 of 46 eyes) and a qualified success rate of 2% (1 of 46 eyes). Fifty-one goniotomy and 11 trabeculotomy procedures were performed. On gonioscopy, the filtration angles were all abnormal with variable width and visibility of the ciliary body band and less visible scleral spur. The trabecular meshwork was seen preoperatively in 100% of eyes (41 of 41 eyes) examined, all of which underwent goniosurgery. Five eyes underwent goniosurgery without documented gonioscopy. The ciliary body band was seen in 39% of eyes (16 of 41 eyes) and the scleral spur was visible in 10% of eyes (4 of 41 eyes). CONCLUSIONS: Goniosurgery is not an effective initial glaucoma surgery for glaucoma associated with Sturge-Weber syndrome. It can be used to temporize the IOP, but ultimately other forms of glaucoma surgery must be considered when indicated. [J Pediatr Ophthalmol Strabismus. 2020;57(6):384-387.].