Understanding Changing Demographic and Treatment Trends of Distal Radius Fractures: A TriNetX Database Contemporary Analysis of 32,912 Patients.

Purpose: Distal radius fractures (DRF) are among the most commonly encountered fractures. The population of the United States is rapidly growing, aging, and diversifying. This study was undertaken to better understand current incidences and treatment trends across all ages, gender, and races to inform resource allocation and to potentially address treatment inequities. Methods: The TriNetX US Collaborative Network was queried for all patients diagnosed with DRFs from 2017 to 2022. Cohorts were defined by inclusion and exclusion of Current Procedural Terminology procedure codes and categorized into operative and nonsurgical groups. Statistical analysis was performed to determine differences in management among demographic groups across the 6-year time period. Results: Incidence rates of operative intervention for DRF increased from 19.6% in 2017 to 23.6% in 2022. Incidence rates of operative intervention increased from 21.7% to 25.2% for females and from 15.3% to 19.7% for males. A bimodal distribution was observed in females with more fractures occurring in the pediatric and geriatric ages, but this distribution was not observed in males. All demographic groups had an overall higher incidence of nonsurgical intervention. Patients aged 40-64 years were more likely to undergo operative intervention than patients 18-39 years. Females were more likely to undergo operative intervention than males. White patients were more likely to undergo operative intervention than Black patients and Asian patients. Conclusions: The incidence of DRFs continues to climb, as does their rate of operative management. The classic bimodal distribution was observed in females, but not males. However, differences in management of DRFs were also observed across different demographic groups with ongoing racial disparities. Future consideration should be taken into optimizing treatment disparities relative to demographic status. Type of Study/Level of Evidence: Prognosis IV.

Incidence and Treatment of Carpal Tunnel Syndrome Following Distal Radius Fractures: A TriNetX Analysis of 39,603 Patients.

Purpose: Distal radius fractures (DRFs) are among the most common fractures and occur among all age groups. Carpal tunnel syndrome (CTS) is a known sequela of DRFs, but its incidence is poorly understood. This study was undertaken to determine the incidence of CTS following a DRF, with the hypothesis being that CTS occurs more commonly after nonsurgical treatment of a DRF. Methods: The TriNetX US Collaborative Network was queried for all patients diagnosed with DRFs from January 2016 to December 2022. Cohorts were defined by inclusion and exclusion of the procedure Current Procedural Terminology codes into surgical and nonsurgical groups and subsequent ICD-10 diagnosis codes of CTS. Statistical analysis was performed to determine differences in management across the study period. Results: A total of 39,603 patients met inclusion with a diagnosis of a DRF. The incidence of CTS within one year of a DRF was 5.3%. Among all DRF cases, 10,279 (26%) patients underwent surgical treatment, whereas 29,324 (74%) patients underwent nonsurgical treatment. The incidence of CTS in the surgical group was 1194 (12%), whereas the incidence of CTS in the nonsurgical group was 915 (3%). Patients undergoing surgical treatment for a DRF had a 9% risk of developing CTS, whereas patients undergoing nonsurgical treatment had a 5% risk. Among all the patients having been diagnosed with CTS, 63% of those with an operatively treated DRF underwent surgical release, whereas 23% of those with a nonoperatively treated DRF underwent surgical release for CTS. Conclusions: Patients having undergone surgical treatment for DRF had a four times higher rate of developing CTS, compared with those having undergone nonsurgical treatment. Among patients who underwent surgical treatment of a DRF with the subsequent development of CTS, there was a nearly three times higher rate of surgical release of CTS. Type of study/level of evidence: Prognostic III.

Understanding the Orthopedic Conditions for Which Patients Are Seeking Medical Cannabis Certification.

BACKGROUND: Amid the ongoing national crisis of opioid misuse in the United States, medical cannabis (MC) has emerged as a potential alternative for chronic pain conditions. This study was performed to understand which orthopedic conditions patients are seeking MC certification for. METHODS: This prospective study was conducted at the Department of Medical Cannabis, Rothman Orthopaedic Institute, Philadelphia, PA, USA. It included consecutive patients with chronic musculoskeletal noncancer pain who were certified for MC, following the Pennsylvania state certification process. Data collected included demographic data, diagnoses, anatomic site of pain, and Patient-Reported Outcomes Measurement Information System (PROMIS) global health scale. The outcome measures from the PROMIS global health scale were used to generate Global Physical Health (GPH) quality of life (QoL) T scores and Global Mental Health (GMH) QoL T scores. RESULTS: A total of 78 patients were available for analysis following initial MC certification, with 50 (64%) being female and 28 (36%) male. The average age was 63 years with 60% of patients in the 65+ age group. Ethnically, 73 (92%) identified as White, and 70 (90%) were not of Hispanic or Latino origin. The most common reason for seeking MC certification was low back pain (56%), followed by neck pain (21%) and then extremity complaints. The mean GPH QoL T score was 43.71 with a standard deviation of ± 9.86 (p-value = 0.001), while the mean GMH QoL T score was 46.85 with a standard deviation of 8.28 (p-value = 0.0015). CONCLUSION: MC cannabis certification was more often sought by women than men and most common for spinal complaints, specifically lower back followed by cervical spine concerns.. This cohort of patients had lower GPH QoL and GMH QoL T scores compared the US general population, representing a significant reduction in the overall physical and mental health.

Therapeutic Effects of Non-Euphorigenic Cannabis Extracts in Osteoarthritis.

Introduction: Osteoarthritis (OA) is disabling and degenerative disease of the joints that is clinically characterized by pain and loss of function. With no disease-modifying treatment available, current therapies aim at pain management but are of limited efficacy. Cannabis products, specifically cannabinoids, are widely used to control pain and inflammation in many diseases with no scientific evidence demonstrating their efficacy in OA. Objective: We investigated the effects of non-euphorigenic cannabis extracts, CBD oil and cannabigerol oil (CBG oil), on pain and disease progression in OA mice. Methods and Results: Twelve-week-old male C57BL/6J mice received either sham or destabilization of the medial meniscus (DMM) surgery. DMM mice were treated with vehicle, CBD oil, or CBG oil. The gait of DMM mice was impaired as early as 2 weeks following surgery and continued deteriorating until week 8, which was restored by CBD oil and CBG oil treatments throughout the disease course. Mechanical allodynia developed in DMM mice, however, was not ameliorated by any of the treatments. On the other hand, both CBD oil and CBG oil ameliorated cold allodynia. In open field test, both oil treatments normalized changes in the locomotor activity of DMM mice. CBD oil and CBG oil treatments significantly reduced synovitis in DMM mice. Only CBG oil reduced cartilage degeneration, chondrocyte loss, and matrix metalloproteinase 13 expression, with a significant increase in the number of anabolic chondrocytes. Subchondral bone remodeling found in vehicle-treated DMM mice was not ameliorated by either CBD or CBG oil. Conclusions: Our results show evidence for the therapeutic efficacy of CBD oil and CBG oil, where both oils ameliorate pain and inflammation, and improve gait and locomotor activity in OA mice, representing clinical pain and function. Importantly, only CBG oil is chondroprotective, which may provide superior efficacy in future studies in OA patients.

Osteochondroma formation is independent of heparanase expression as revealed in a mouse model of hereditary multiple exostoses.

Hereditary multiple exostoses (HME) is a rare, pediatric disorder characterized by osteochondromas that form along growth plates and provoke significant musculoskeletal problems. HME is caused by mutations in heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2. Seemingly paradoxically, osteochondromas were found to contain excessive extracellular heparanase (Hpse) that could further reduce HS levels and exacerbate pathogenesis. To test Hpse roles, we asked whether its ablation would protect against osteochondroma formation in a conditional HME model consisting of mice bearing floxed Ext1 alleles in Agr-CreER background (Ext1f/f ;Agr-CreER mice). Mice were crossed with a new global Hpse-null (Hpse-/- ) mice to produce compound Hpse-/- ;Ext1f/f ;Agr-CreER mice. Tamoxifen injection of standard juvenile Ext1f/f ;Agr-CreER mice elicited stochastic Ext1 ablation in growth plate and perichondrium, followed by osteochondroma formation, as revealed by microcomputed tomography and histochemistry. When we examined companion conditional Ext1-deficient mice lacking Hpse also, we detected no major decreases in osteochondroma number, skeletal distribution, and overall structure by the analytical criteria above. The Ext1 mutants used here closely mimic human HME pathogenesis, but have not been previously tested for responsiveness to treatments. To exclude some innate therapeutic resistance in this stochastic model, tamoxifen-injected Ext1f/f ;Agr-CreER mice were administered daily doses of the retinoid Palovarotene, previously shown to prevent ectopic cartilage and bone formation in other mouse disease models. This treatment did inhibit osteochondroma formation compared with vehicle-treated mice. Our data indicate that heparanase is not a major factor in osteochondroma initiation and accumulation in mice. Possible roles of heparanase upregulation in disease severity in patients are discussed.

Premature Growth Plate Closure Caused by a Hedgehog Cancer Drug Is Preventable by Co-Administration of a Retinoid Antagonist in Mice.

The growth plates are key engines of skeletal development and growth and contain a top reserve zone followed by maturation zones of proliferating, prehypertrophic, and hypertrophic/mineralizing chondrocytes. Trauma or drug treatment of certain disorders can derange the growth plates and cause accelerated maturation and premature closure, one example being anti-hedgehog drugs such as LDE225 (Sonidegib) used against pediatric brain malignancies. Here we tested whether such acceleration and closure in LDE225-treated mice could be prevented by co-administration of a selective retinoid antagonist, based on previous studies showing that retinoid antagonists can slow down chondrocyte maturation rates. Treatment of juvenile mice with an experimental dose of LDE225 for 2 days (100 mg/kg by gavage) initially caused a significant shortening of long bone growth plates, with concomitant decreases in chondrocyte proliferation; expression of Indian hedgehog, Sox9, and other key genes; and surprisingly, the number of reserve progenitors. Growth plate involution followed with time, leading to impaired long bone lengthening. Mechanistically, LDE225 treatment markedly decreased the expression of retinoid catabolic enzyme Cyp26b1 within growth plate, whereas it increased and broadened the expression of retinoid synthesizing enzyme Raldh3, thus subverting normal homeostatic retinoid circuitries and in turn accelerating maturation and closure. All such severe skeletal and molecular changes were prevented when LDE-treated mice were co-administered the selective retinoid antagonist CD2665 (1.5 mg/kg/d), a drug targeting retinoid acid receptor γ, which is most abundantly expressed in growth plate. When given alone, CD2665 elicited the expected maturation delay and growth plate expansion. In vitro data showed that LDE225 acted directly to dampen chondrogenic phenotypic expression, a response fully reversed by CD2665 co-treatment. In sum, our proof-of-principle data indicate that drug-induced premature growth plate closures can be prevented or delayed by targeting a separate phenotypic regulatory mechanism in chondrocytes. The translation applicability of the findings remains to be studied. © 2021 American Society for Bone and Mineral Research (ASBMR).

Activin A promotes the development of acquired heterotopic ossification and is an effective target for disease attenuation in mice.

Heterotopic ossification (HO) is a common, potentially debilitating pathology that is instigated by inflammation caused by tissue damage or other insults, which is followed by chondrogenesis, osteogenesis, and extraskeletal bone accumulation. Current remedies are not very effective and have side effects, including the risk of triggering additional HO. The TGF-ß family member activin A is produced by activated macrophages and other inflammatory cells and stimulates the intracellular effectors SMAD2 and SMAD3 (SMAD2/3). Because HO starts with inflammation and because SMAD2/3 activation is chondrogenic, we tested whether activin A stimulated HO development. Using mouse models of acquired intramuscular and subdermal HO, we found that blockage of endogenous activin A by a systemically administered neutralizing antibody reduced HO development and bone accumulation. Single-cell RNA-seq analysis and developmental trajectories showed that the antibody treatment reduced the recruitment of Sox9+ skeletal progenitors, many of which also expressed the gene encoding activin A (Inhba), to HO sites. Gain-of-function assays showed that activin A enhanced the chondrogenic differentiation of progenitor cells through SMAD2/3 signaling, and inclusion of activin A in HO-inducing implants enhanced HO development in vivo. Together, our data reveal that activin A is a critical upstream signaling stimulator of acquired HO in mice and could represent an effective therapeutic target against forms of this pathology in patients.

Human and mouse activin genes: Divergent expression of activin A protein variants and identification of a novel heparan sulfate-binding domain in activin B.

Activins are members of the transforming growth factor-ß (TGF-ß) superfamily of signaling proteins and were originally identified as components of follicular fluid. The proteins are now known to play critical roles in numerous normal and pathological processes and conditions, but less is clear about the relationships between their gene organization and protein variant expression and structure. The four human and mouse activin (Act) genes, termed INHßA, INHßB, INHßC and INHßE, differ in exon numbers. Human INHßA is the most complex with 7 exons and elicits production of three Act A variants (Act A X1, X2 and X3) differing in their pro-region, as we showed previously. Here we further analyzed the mouse INHßA gene and found that its 4 exons encode for a single open reading frame (mouse Act A), corresponding to the shortest human Act A X3 variant. Activins are synthesized and secreted as large complexes made of a long pro-region and a short mature C- terminal ligand and are known to interact with the heparan sulfate (HS) chains of cell surface and matrix proteoglycans. Human Act A X1 and X2 variants do have a HS-binding domain (HBD) with Cardin/Weintraub traits in their pro-region, while the X3 variant does not as shown previously. We found that the mouse Act A lacks a HBD as well. However, we identified a typical HBD in the pro-region of both mouse and human Act B, and synthetic peptides containing that domain interacted with immobilized HS and cell surface with nanomolar affinity. In sum, human and mouse Act A genes elicit expression of different variant sets, while there is concordance in Act B protein expression, reflecting possible evolutionary diversity in function of, and responses to, these signaling proteins in the two species.

Outcomes of surgical bleb revision for late-onset bleb leaks after trabeculectomy.

PURPOSE: To describe the outcome of surgical bleb revision for late-onset bleb leaks after trabeculectomy. PATIENTS AND METHODS: Appropriate cases were identified. Qualified and complete success required intraocular pressure of 21 mm Hg or less with and without glaucoma medication use, respectively. Bleb survival was determined using Kaplan-Meier survival analysis, and overall success rate was defined as qualified success at last follow-up. Preoperative and postoperative ocular parameters were compared using the signed-rank test. Age, sex, ethnicity, time between leak and revision, and surgeon type (attending vs. surgeons in training) were entered into a logistic regression analysis to assess the impact on surgical outcome. RESULTS: Seventy-eight eyes of 75 patients were included. The overall rate of successful bleb revision was 77%, and qualified and complete success at 24 months was 71% and 34%, respectively. Postoperative complications included early and late bleb leaks in 6% and 9% of the eyes, respectively; bleb-related infections in 4% of the eyes; and the need for additional glaucoma surgery in 10% of the eyes. There was no difference in preoperative and postoperative visual acuity (P=0.34) but there was an increase in intraocular pressure (P<0.0001) and the number of medications used (P<0.0001). The number of eyes that did not require glaucoma medication decreased (P=0.002). None of the variables examined had a significant impact on successful surgical outcome. CONCLUSION: Bleb revision showed a high success rate. About two-thirds of eyes required medication, 10% of eyes required additional glaucoma surgery, and there was a low risk for bleb-related infection following bleb revision.

Midface lifting as an adjunct procedure in ectropion repair.

PURPOSE: To evaluate the efficacy of ectropion repair with adjunctive midface lift. METHODS: Retrospective chart review of patients with cicatricial, involutional, or paralytic ectropion with midface descent. Ectropion repair with adjunctive supraperiosteal midface lifting was performed on each patient. Surgical indications included lower eyelid ectropion, lagophthalmos, and/or cosmetic deformity. Outcomes analyzed were recurrence or adequacy of ectropion correction, complications, and need for further surgery. Surgical success was determined by the need for further surgery. RESULTS: A total of 32 procedures performed on 22 patients undergoing ectropion repair with adjunctive supraperiosteal midface lift were reviewed. Of the 15 procedures for patients with cicatricial ectropion, 80% (12 of 15 procedures) had improvement of lower eyelid position, without the need for further surgery; 71.4% of procedures for involutional ectropion (10 of 14 procedures) resulted in improvement in lower eyelid position, without the need for further surgery. There was improvement in ectropion in all patients with paralytic ectropion and no recurrences. A total of 5 patients had recurrences after ectropion repair with midface lift secondary to perioperative complications, a shortage of anterior lamella, or due to a heavy midface. CONCLUSIONS: We demonstrated that most patients undergoing midface lift in addition to ectropion repair have a favorable result. This is to be expected, given the close anatomic relationship between the lower eyelid and the midface. A midface lift should be considered in all patients who have both ectropion and significant midface descent.

Estimates of ocular and visual retention following treatment of extra-large uveal melanomas by proton beam radiotherapy.

OBJECTIVE: To assess outcomes of proton beam radiotherapy for the treatment of extra-large uveal melanomas in patients specifically referred to the University of California, San Francisco, for ocular conservation therapy. Series patients uniformly refused enucleation both at an outside institution and again as a treatment option after extensive discussion at the University of California, San Francisco. DESIGN: In a retrospective, nonrandomized cohort study, 21 patients with extra-large choroidal or ciliochoroidal melanomas measuring at least 10 mm in maximum thickness or 20 mm in maximum basal diameter or tumors located within 3 mm of the optic nerve measuring at least 8 mm in maximum thickness or 16 mm in maximum basal diameter met inclusion criteria. Main outcome measures were frequency of (1) anterior segment complications (lash loss, keratopathy, cataract, and neovascular glaucoma), (2) posterior segment complications (vitreous hemorrhage, radiation retinopathy, and radiation papillopathy), (3) treatment failure (tumor growth, enucleation, or metastases), and (4) final visual acuity. RESULTS: Median follow-up was 28 months. Mean age at treatment was 58.3 years. The frequencies of hypertension and diabetes mellitus were 14.3% and 9.5%, respectively. Mean tumor thickness and mean basal diameter were 8.6 mm and 18.7 mm, respectively. Lash loss occurred in 52.4%; dry eye, in 23.8%; cataract, in 28.6%; neovascular glaucoma, in 38.1% (100% in patients with diabetes mellitus); radiation retinopathy, in 9.5%; and radiation papillopathy, in 9.5%. No patient developed radiation-associated scleral necrosis or vitreous hemorrhage. The 2-year Kaplan-Meier estimate of local tumor growth after treatment was 33%, and the rate of distant metastasis was 10%. Visual acuity of 20/200 or better was preserved in 25% of patients, including 4 patients (19%) who experienced an average of 4 lines of Snellen visual acuity improvement. Development of neovascular glaucoma was associated with tumors in close proximity to the optic nerve (P = .04), while cataract (P = .03) and lash loss (P = .02) occurred with more anteriorly located tumors. Proton beam radiotherapy provided a 67% probability of local control and 90% probability of clinically discernible metastases-free survival at 24 months after treatment. CONCLUSION: Proton beam radiotherapy is an ocular-conserving option that may be considered for the treatment of extra-large uveal melanoma in carefully selected patients.

Optical coherence tomography in unilateral resolved central serous chorioretinopathy.

PURPOSE: To evaluate the correlation between optical coherence tomographic evaluations of foveal thickness and anatomical changes within the fovea and visual acuity in patients who have unilateral resolved central serous chorioretinopathy. METHODS: A retrospective review of cases of unilateral resolved central serous chorioretinopathy imaged with high-resolution optical coherence tomography was performed. The foveal thickness of the involved eye was normalized by dividing its thickness by that of the uninvolved fellow eye. The best-corrected visual acuity of the involved eye was normalized as well. The normalized foveal thickness was compared with the normalized visual acuity. The anatomical findings of the fovea were compared with the visual acuity. RESULTS: Twenty patients were evaluated (11 men and 9 women; age range, 31-66 years [mean, 46.8 years]). The mean foveal thickness was 135.8 mum in the involved eyes and 184.4 mum in the uninvolved eyes (P < 0.001). There was a correlation between the normalized foveal thickness and the normalized visual acuity (Spearman rho, 0.67; P = 0.001). The external limiting membrane was visible in 7 (35%) of the involved eyes compared with 19 uninvolved eyes (95%) (P < 0.001). In the involved eyes, those with a visible external limiting membrane had better visual acuity than did those that did not (P = 0.001). It was possible to visualize the boundary between the photoreceptor cell bodies and the outer segments in 8 (40%) of the involved eyes and in the 17 uninvolved eyes (85%) (P < 0.001). In the involved eyes, those with a visible boundary between the photoreceptor bodies and the outer segments had a better visual acuity than did those that did not (P = 0.019). CONCLUSIONS: Patients with unilateral resolved central serous chorioretinopathy had a decrease in the central foveal thickness in the involved eyes, and there was a statistically significant correlation between the foveal thickness and the visual acuity, even in eyes with relatively good visual acuity. The inability to observe a discrete signal corresponding to the external limiting membrane layer was more common in involved eyes and was significantly associated with decreased visual acuity. This same relationship was seen with the ability to visualize the boundary between the photoreceptor bodies and the outer segments; this boundary was less commonly observed in involved eyes and was associated with decreased visual acuity. Resolved central serous chorioretinopathy causes a number of morphologic changes in the fovea that are associated with visual acuity.

Intraretinal silicone oil vacuoles after macular hole surgery with internal limiting membrane peeling.

PURPOSE: To report the detection of intraretinal silicone oil vacuoles after the use of a silicone oil tamponade for macular hole surgery with internal limiting membrane (ILM) peeling. DESIGN: Observational case report. METHODS: A 57-year-old woman with a recurrent macular hole in the left eye underwent macular hole surgery with ILM peeling and silicone oil tamponade. After early silicone oil emulsification was detected, the silicone oil was removed. RESULTS: Follow-up ophthalmoscopic examination and optical coherence tomography imaging revealed intraretinal silicone oil vacuoles in the area of ILM peeling. CONCLUSIONS: Internal limiting membrane defects may facilitate the entry of silicone oil into the retina, leading to accumulation of oil vacuoles. The use of silicone oil in macular hole surgery with ILM peeling may complicate the postoperative outcome.