Rising incidence of stair-related upper extremity fractures among older adults in the United States: a 10-year nationwide analysis.

Upper extremity (UE) fractures are prevalent age-related fractures, and stair-associated falls are a common mechanism for these injuries. Our study has identified an increasing incidence of stair-related UE fractures and associated hospitalization rates among the older United States population between 2012-2021. Targeted prevention efforts should be implemented by health systems. INTRODUCTION: To analyze United States (US) emergency department trends in upper extremity stair-related fractures among older adults and investigate risk factors associated with hospitalization. METHODS: We queried the National Electronic Injury Surveillance System (NEISS) for all stair-related fracture injuries between 2012 and 2021 among adults 65 years or older. The US Census Bureau International Database (IDB) was analyzed to calculate incidence rates. Descriptive analysis, linear regression analysis, and multivariate regression analysis were used to interpret the collected data. RESULTS: Our analysis estimated 251,041 (95% CI: 211,678-290,404) upper extremity stair-related fractures among older adults occurred between 2012 and 2021. The primary anatomical locations were the humeral shaft (27%), wrist (26%), and proximal humerus (18%). We found a 56% increase in injuries (R2 = 0.77, p < 0.001), 7% increase in incidence per 100,000 persons (R2 = 0.42, p < 0.05), and an 38% increase in hospitalization rate (R2 = 0.61, p < 0.01) during the 10-year study period. Women sustained the majority of fractures (76%) and most injuries occurred in homes (89%). Advanced age (p < 0.0001), males (p < 0.0001), proximal humerus fractures (p < 0.0001), humeral shaft fractures (p < 0.0001), and elbow fractures (p < 0.0001) were associated with increased odds of hospitalization after injury. CONCLUSION: Stair-related UE fracture injuries, incidence, and hospitalization rates among older adults are increasing significantly, particularly among older females. Improving bone health, optimizing functional muscle mass, and "fall-proofing" homes of older age groups may help mitigate the rising incidence of these injuries.

Displacement of diaphyseal clavicle fractures related to patient position and progressive displacement in the peri-injury period.

BACKGROUND: The purposes of this study were (1) to determine how supine versus upright patient position affects the measurement of diaphyseal clavicle fracture displacement, (2) to describe the incidence of progressive displacement in the peri-injury period, and (3) to investigate variables associated with the progressive displacement. METHODS: Between 2013 and 2015, patients aged 14 years or older presenting with a diaphyseal clavicle fracture within 7 days of injury were included (N = 50). A well-defined radiographic protocol was established. Nine patients underwent surgery after the second follow-up, and the remaining 41 patients, who did not undergo surgery, received the full complement of measures at the first, second, and third follow-up time points. The second follow-up (8-21 days after injury) and third follow-up (22-60 days after injury) had the same defined radiographic protocol as the first visit. The amount of displacement and angulation was measured in both the supine and upright positions on the initial injury radiographs and subsequent follow-up radiographs. RESULTS: Vertical translation was 2.4 mm (95% confidence interval, 1.8-3.0 mm) greater and angulation was 3.9° (95% confidence interval, 3.3°-4.6°) greater in the upright position. Progressive displacement occurred in 16 patients (32%). Older age (P = .015) and ipsilateral shoulder girdle or chest wall injury (P = .007) were significantly associated with progressive displacement. CONCLUSIONS: Upright radiographs evaluate maximal displacement in diaphyseal clavicle fractures. Close follow-up of nonoperatively treated clavicle fractures is warranted. Progressive displacement was more likely in older patients and/or those who had ipsilateral shoulder girdle or chest wall injury.

Hospital-Treated Falls and Comorbidities Among Older Adults in Minnesota, 2010-2014.

Falls are a serious concern for older adults as they frequently result in injury, disability and even death. In older adults in Minnesota, the number and rate of hospital-treated falls have been increasing, for both males and females. The purpose of this study was to estimate trends in falls among older adults in Minnesota, and to examine whether there is an association between severe outcomes of falls and predictors. We investigated hospital-treated (both emergency department treatment and hospitalizations) falls among adults 65 years and older in Minnesota between 2010 and 2014, using hospital discharge data from the Minnesota Hospital Association. In total, 199,364 cases were identified; this represents a rate of 5,281.4/100,000 during the five-year period. We found the number of hospital-treated falls increased each year by 1,820 cases on average, for an average rate increase of 108.3/100,000 per year. The rate for falls with no comorbidities decreased, while the rate for falls with one or more comorbidities increased: Also, comorbidities were more likely among hospitalized and/ or fatal cases than among nonhospitalized and/or nonfatal cases. The most frequent principal injury diagnoses associated with falls included fractures (31.7% of total hospital-treated falls), superficial wounds/contusions (14.7%), open wounds (10.9%) and traumatic brain injuries (TBIs) (3.9%). The most frequent type of fracture was hip fracture (29.1 %). Additional complications commonly occurring during hospital treatment of injury resulting from a fall included urinarytract infection (7.2%), pneumonia (2.2%), pressure ulcer (1.2%) and sepsis (0.9%). Among these, sepsis had the highest odds ratio of 9.9 for death. These data show the burden of falls is greatest among those who are 85 and older and/or who have one or more comorbidities.

Acute corneal toxicity of latanoprost with different preservatives.

PURPOSE: To investigate the corneal toxicity of Xalatan and three latanoprost generics using transepithelial electrical resistance (TER) and scanning electron microscopy (SEM). METHODS: Corneal TER changes after a 60-s exposure to Xalatan (latanoprost 0.005% preserved with 0.02% BAC), and latanoprost generics (Latanoprost PF BAC free, Latanoprost Nitten SB containing sodium benzoate and Latanoprost Towa containing 0.01% BAC with sodium chloride polysorbate 80 as additive) were measured in living rabbits. Corneal damage was also examined by SEM. Hank's balanced salt solution (HBSS) was used as a control. RESULTS: There was a significant decrease in the corneal TER after exposure of the cornea to Xalatan (p < 0.01) and all latanoprost generics (p < 0.01: Latanoprost PF, p < 0.05: Latanoprost Nitten SB, Latanoprost Towa) as compared to HBSS. All latanoprost generics showed less TER decrease in the corneal TER as compared to Xalatan (p < 0.01). SEM revealed that superficial cells of Xalatan-treated corneas were damaged and exhibited degenerated microvilli. Conversely, the superficial cells of corneas exposed to HBSS or all latanoprost generics appeared normal and had normal microvilli under SEM examinations. CONCLUSION: The corneal toxicity of Xalatan is greater than that of latanoprost generics. Xalatan contains 0.02% BAC, which may be responsible for the corneal toxicity.

Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation.

OBJECTIVE: To investigate the expression and function of Mohawk (MKX) in human adult anterior cruciate ligament (ACL) tissue and ligament cells from normal and osteoarthritis (OA)-affected knees. METHODS: Knee joints were obtained at autopsy (within 24-48 hours postmortem) from 13 donors with normal knees (mean ± SD age 36.9 ± 11.0 years), 16 donors with knee OA (age 79.7 ± 11.4 years), and 8 aging donors without knee OA (age 76.9 ± 12.9 years). All cartilage surfaces were graded macroscopically. MKX expression was analyzed by immunohistochemistry and quantitative polymerase chain reaction. ACL-derived cells were used to study regulation of MKX expression by interleukin-1ß (IL-1ß). MKX was knocked down with small interfering RNA (siRNA) to analyze the function of MKX in extracellular matrix (ECM) production and differentiation in ACL-derived cells. RESULTS: The expression of MKX was significantly decreased in ACL-derived cells from OA knees compared with normal knees. Consistent with this finding, immunohistochemistry analysis showed that MKX-positive cells were significantly reduced in ACL tissue from OA donors, in particular in cells located in disorientated fibers. In ACL-derived cells, IL-1ß strongly suppressed MKX expression and reduced expression of the ligament ECM genes COL1A1 and TNXB. In contrast, SOX9, a chondrocyte master transcription factor, was up-regulated by IL-1ß treatment. Importantly, knockdown of MKX expression with siRNA up-regulated SOX9 expression in ACL-derived cells, whereas the expression of COL1A1 and TNXB was reduced. CONCLUSION: Reduced expression of MKX is a feature of degenerated ACL in OA-affected joints, and this may be mediated in part by IL-1ß. MKX appears necessary to maintain the tissue-specific cellular differentiation status and ECM production in adult human tendons and ligaments.

The Mohawk homeobox transcription factor regulates the differentiation of tendons and volar plates.

BACKGROUND: Mohawk (Mkx) is a homeodomain-containing transcription factor that is expressed in various mesoderm-derived tissues, particularly in developing tendons. In this study, we investigate the exact expression pattern and functions of Mkx in forelimbs. METHODS: We analyzed the forelimbs of Mkx knockout mice [from embryonic day (E) 18.5 to postnatal day (P) 28 weeks] by using knocked-in Venus signals, Masson trichrome staining, and hematoxylin and eosin (H&E) staining. RESULTS: We detected Venus signals in forelimb tendons, pulleys, and volar plates (VPs) in P21 mice. In-depth histological analysis showed that compared to the wild-type mice, the Mkx knockout mice showed significant hypoplasia in the flexor digitorum profundus tendons from E18.5. The VPs and pulleys appeared normal until P0; however, by P14, they became increasingly thicker in Mkx-null mice compared to wild-type mice. The fiber alignment was particularly disrupted in VPs of Mkx-null mice. CONCLUSIONS: These results suggest that Mkx is an important regulator of the differentiation of VPs and pulleys, as well as of tendon differentiation.

Disparities in Osteoporosis Prevention and Care: Understanding Gender, Racial, and Ethnic Dynamics.

PURPOSE: Osteoporosis, the most prevalent metabolic bone disease, significantly impacts global public health by increasing fracture risks, particularly among post-menopausal women and the elderly. Osteoporosis is characterized by decreased bone mineral density (BMD) and deterioration of bone tissue, which leads to enhanced fragility. The disease is predominantly diagnosed using dual X-ray absorptiometry (DXA) and is significantly influenced by demographic factors such as age and hormonal changes. This chapter delves into the condition's complex nature, emphasizing the pervasive gender and racial disparities in its screening, diagnosis, and treatment. RECENT FINDINGS: Recent findings highlight a substantial gap in the management of osteoporosis, with many individuals remaining under-screened and under-treated. Factors contributing to this include the asymptomatic early stages of the disease, lack of awareness, economic barriers, and inconsistent screening practices, especially in under-resourced areas. These challenges are compounded by disparities that affect different genders and races unevenly, influencing both the prevalence of the disease and the likelihood of receiving adequate healthcare services. The summary of this chapter underscores the urgent need for targeted strategies to overcome these barriers and improve health equity in osteoporosis care. Proposed strategies include enhancing public and healthcare provider awareness of osteoporosis, broadening access to diagnostic screenings, and integrating personalized treatment approaches. These efforts aim to align with global health objectives to mitigate the impacts of osteoporosis and ensure equitable health outcomes across all demographic groups.

Timing of Complications Following Surgery for Distal Femur Fractures in Older Adults.

Introduction: The purpose of this study was to identify the timing and nature of complications associated with distal femur fracture surgery in patients aged 65 and older using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Methods: The ACS NSQIP database was queried for adults aged 65 and older who received surgical treatment for a distal femur fracture between 01 January 2015 and 31 December 2021. Cox regression models and risk tables adjusted for baseline clinical characteristics were created for 14 complications (Superficial Surgical Site Infection (SSI), Deep SSI, Organ/Space SSI, Pneumonia, Pulmonary Embolism (PE), Deep Venous Thrombosis (DVT), Urinary Tract Infection (UTI), Stroke/Cerebrovascular accident (CVA), Myocardial Infarction (MI), Renal Failure, Cardiac Arrest (CA), Re-operation, Sepsis, and Death within 30 days of surgery). Model summaries were used to identify significant variables with a Bonferroni correction applied. Results: A total of 3956 adults met inclusion criteria and were included in analysis. The most common complications were UTI (5.2%), death (4.1%), and pneumonia (3.4%). Complications typically occurred within 14 days after surgery, except for SSI, which occurred between post-op days 11 and 24. Conclusions: Distal femur fractures are a substantial source of morbidity and mortality in the older adult population. Our findings underscore the need for comprehensive preoperative risk assessment and patient management strategies to mitigate the impact of identified risk factors in this vulnerable population.

Medial femoral circumflex artery pseudoaneurysm following intramedullary nailing for intertrochanteric fracture.

CASE: We present the case of a 92-year-old woman who developed a medial femoral circumflex artery (MFCA) pseudoaneurysm intraoperatively while obtaining reduction during intramedullary nailing (IMN) for intertrochanteric fracture. CONCLUSIONS: Pseudoaneurysms are rare vascular complications in hip fracture surgery. Early recognition of signs and symptoms of this phenomenon are essential for diagnosis and treatment. Close post-operative monitoring and serial hemoglobin should be considered for unexplained intra-operative bleeding. A low threshold for angiography should be entertained if active bleeding and clinical decompensation occur during instrumented percutaneous pertrochanteric fracture reduction. This patient underwent conventional angiography with successful coil embolization and exclusion of the MFCA pseudoaneurysm.

Hip fracture care during the COVID-19 pandemic: retrospective cohort and literature review.

OBJECTIVES: The goal of this study was to investigate whether the COVID-19 pandemic has affected hip fracture care at a Level I Trauma hospital. The secondary goal was to summarize the published hip fracture reports during the pandemic. DESIGN: A retrospective cohort study. SETTING: Level I Trauma Center. PATIENTS/PARTICIPANTS: Eighty-six operatively treated hip fracture patients age ≥65 years, occurring from January 17 to July 2, 2020. INTERVENTION IF ANY: N/A. MAIN OUTCOME MEASUREMENTS: We defined 3 phases of healthcare system response: pre-COVID-19 (period A), acute phase (period B), and subacute phase (period C). The primary outcome was 30-day mortality. Clinical outcomes including time to surgery (TTS) and length of stay (LOS) were extracted from the electronic medical record. RESULTS: Twenty-seven patients from Period A, 27 patients from Period B, and 32 patients from Period C were included. The 30-day mortality was not statistically different. The mean TTS was 20.0 +/- 14.3 hours and was the longest in Period C (22.1 +/- 9.8 hours), but the difference was not statistically significant. The mean LOS was 113.0 +/- 66.2 hours and was longest in Period B (120.9 +/- 100.6 hours). However, the difference was not statistically significant. CONCLUSIONS: The 30-day mortality, TTS, and LOS were not statistically different across multiple phases of pandemic at a level 1 trauma center. Our results suggest that we successfully adapted new protocol changes and continued to provide evidence-based care for hip fracture patients. Our results were comparable with that of other authors around the world.

Low-energy suspiciously open proximal humerus fracture management in older adult patient: A case report.

Although fractures of the proximal humerus are common among older adults, open fractures following low-energy trauma are exceptionally rare. Prior studies have alluded to the existence of this injury, but there are no detailed reports on its presentation, management, or long-term follow-up. We present the case of a 78-year-old man that sustained a suspiciously open proximal humerus fracture of the dominant hand following a fall down a few stairs. Management consisted of early intravenous antibiotics followed by open reduction and internal fixation with irrigation and debridement. Intraoperative soft tissue assessment revealed a wound extending from bone to skin. The patient suffered no complications, regained full function of his arm, and is pain free. Considering the rarity of this injury and its potential for highly morbid complications, this case serves as a reminder that we should continue to have a low suspicion threshold for open fracture when punctures or lesions are present around proximal humerus fractures, even for low-energy injuries. Prompt and thorough examination, initiation of antibiotics, and surgical intervention are keys to providing best care for this uncommon injury.

Outcomes After Revision Fixation With Cement Augmentation for Failed Intertrochanteric Fracture Fixation in Older Adult Patients.

Introduction: Intertrochanteric (IT) fractures that fail fixation are traditionally treated with arthroplasty, introducing significant risk of morbidity and mortality in frail older adult patients. Revision fixation with cement augmentation is a relatively novel technique that has been reported in several small scale international studies. Here we report a clinical series of 22 patients that underwent revision fixation with cement augmentation for IT fracture fixation failure. Methods: This retrospective case series identified all patients that underwent revision intramedullary nailing from 2018 to 2021 at two institutions within a large metropolitan healthcare system. Demographics, injury characteristics, Charlson Comorbidity Index score, and surgical characteristics were extracted from the electronic medical record. Outcomes were extracted from the electronic medical record and included radiographic findings, pain, functional outcomes, complications, and mortality. Results: Average follow-up after revision surgery was 15.2 ± 10.6 months. Twenty patients (90.9%) reported improved pain and achieved union or progressive healing after surgery. Most of these patients regained some degree of independent ambulation (19 patients, 86.4%), with only 5 patients (22.7%) requiring increased assistance for their activities of daily living (ADLs). One-year mortality was 13.6% (3 patients). Of the 5 patients (22.7%) that experienced complications, 2 patients (9.1%) required revision hemiarthroplasty for subsequent fixation failure. The other 3 patients did well when complications resolved. Conclusions: Revision fixation with cement augmentation can be an effective, safe, cost-effective alternative to arthroplasty for the management of cases involving non-infected failed IT fracture fixation with implant cut-out or cut-through limited to the femoral head in older adult patients that have appropriate acetabular bone stock.

A quality improvement project addressing the underreporting of delirium in hip fracture patients.

INTRODUCTION: After discovering a low incidence of delirium for hip fracture patients at our institution, we evaluated if this was due to underreporting and, if so, where process errors occurred. METHODS: Hip fracture patients aged ≥60 with a diagnosis of delirium were identified. Chart-Based Delirium Identification Instrument (CHART-DEL) identified missed diagnoses of delirium. Process maps were created based off staff interviews and observations. RESULTS: The incidence of delirium was 15.3% (N = 176). Within a random sample (n = 98), 15 patients (15.5%) were diagnosed, while 20 (24.7%) went undiagnosed despite evidence of delirium. Including missed diagnoses, delirium prevalence was higher in the sample compared to all patients (35.7% vs 15.3%, p < 0.001). Most missed diagnoses were due to failure in identifying delirium (60%) or failure in documenting/coding diagnosis (20%). The prevalence of baseline cognitive impairment was higher in undiagnosed delirium patients versus correctly diagnosed patients (80% vs 20%, p = 0.001). CONCLUSIONS: Our institution significantly underreports delirium among hip fracture patients mainly due to; (1) failure to identify delirium by the clinical staff, and (2) failure to document/code diagnosis despite correct identification. Baseline cognitive impairment can render delirium diagnosis challenging. These serve as targets for quality improvement and hip fracture care enhancement.

Management of Geriatric Elbow Injury.

Approximately 4.1% of all fractures in the elderly involve the elbow. Most elbow injuries in geriatric patients occur as the result of low-energy mechanisms such as falls from standing height. Elbow injuries in elderly patients present complex challenges because of insufficient bone quality, comminution, articular fragmentation, and preexisting conditions, such as arthritis. Medical comorbidities and baseline level of function must be heavily considered in surgical decision making.

Outcomes of COVID-19 Negative Hip Fracture Patients During the Acute and Subacute Pandemic.

OBJECTIVES: To better elucidate how the COVID-19 pandemic has affected the operatively treated geriatric hip fracture population and how the health care system adapted to pandemic dictated procedures. DESIGN: Retrospective cohort study. SETTING: A community hospital. PARTICIPANTS: Individuals ≥65 years of age presented with a proximal femoral fracture from a low-energy mechanism undergoing operative treatment from January 17, 2020 to July 2, 2020 (N = 125). MEASUREMENTS: We defined 3 phases of healthcare system response: pre-COVID-19, acute phase, and subacute phase. Thirty-day mortality, time to operating room (OR), length of stay, time to start physical therapy, perioperative complications, delirium rate, hospice admission rate, discharge dispositions, readmission rate, and the reason of surgery delay were assessed. RESULTS: The number of hip fractures has remained constant during the pandemic. The 30-day mortality rate, time to OR, and length of stay were higher in the pandemic compared to the pre-pandemic. Those who had a longer wait time to OR (≥ 24 hours) had more complications and increased 30-day mortality rates. Some of the surgery delays were related to OR unavailability as a consequence of the COVID-19 pandemic. Surgery was delayed in 3 patients who were on direct oral anticoagulants (DOACs) in pandemic but none for pre-pandemic period. CONCLUSION: This is the first study to compare the effect of the acute and subacute phases of the pandemic on uninfected hip fracture patients. In the age of COVID-19, to provide the best care for the vulnerable geriatric orthopedic populations, the healthcare system must adopt new protocols. We should still aim to promote prompt surgical care when indicated. It is important to ensure adequate resource availability, such as OR time and staff so that hip fracture patients may continue to receive rapid access to surgery. A multidisciplinary approach remains the key to the management of fragility hip fracture patients during the pandemic.

Evaluation of retinal blood flow before and after panretinal photocoagulation using pattern scan laser for diabetic retinopathy.

PURPOSE: Laser speckle flowgraphy (LSFG) can measure blood flow in the ocular fundus. We analyzed the relationship between retinal blood flow and panretinal photocoagulation (PRP) in diabetic retinopathy. METHODS: This retrospective observational study examined the eyes of 35 patients with proliferative diabetic retinopathy (PDR) or non-PDR (NPDR). PRP was performed using a pattern scan laser. Using LSFG, blood flow was evaluated as the mean blur rate (MBR) or the relative flow volume (RFV). We also evaluated MBR in the vessels of the optic nerve head (MBR-V), RFV at the first retinal artery (RFV-A), and RFV at the first retinal vein (RFV-V) before bifurcation. Blood flows were measured prior to treatment initiation, during each PRP session, and after PRP. RESULTS: The total number of laser spots created was 4258 ± 461. Regression of neovascular activity at 6 months after PRP occurred in 29 (82.85%) eyes. MBR-V significantly decreased to 83.9 ± 16% (p = .0039), 79.3 ± 21% (p = .0001), and 73.5 ± 26% (p = .0001) after the first, second, and third PRP treatment sessions. MBR-V was also reduced to 75.0 ± 25% (p = .0001), 75.0 ± 25% (p = .0001), and 80.3 ± 22% (p = .0001) at 1, 3, and 6 months following PRP. During and at 6 months after the PRP treatments, RFV-A and RFV-V were also significantly reduced (p< .01). CONCLUSIONS: During and after PRP treatments using pattern scan laser, retinal blood flow was reduced. Retinal blood flow may be an auxiliary measurement for effectively evaluating PRP or PDR.

[Effects of implementing clinical pathways for the care of patients undergoing ophthalmic surgery for cataract, glaucoma, and vitreoretinal disorder].

PURPOSE: To evaluate the actual use of clinical pathways and variances, and compare the length of hospital stay for surgery of cataract, glaucoma, and vitreoretinal disorder. METHODS: We designed eight types of clinical pathways for the treatment of cataract, glaucoma, and retinal-vitreous disease. We performed 102 phacoemulsifications and intraocular lens (IOL) implantations, 19 glaucoma or combined trabeculotomy and phacoemulsification/IOL, and 69 retinal-vitreous surgeries during a 1-year period from February 2002. We compared the length of the hospital stay before and after clinical pathway implementation. RESULTS: We applied the clinical pathways to 102 eyes (100%) of 67 patients undergoing phacoemulsification/IOL, to 17 eyes (89.5%) of those undergoing glaucoma surgery, and to 69 eyes (100%) of those undergoing retinal-vitreous surgery. The vaiances occurred in 20 eyes (29.9%) of 67 phacoemulsification/IOLs, 6 eyes (31.6%) of glaucoma, and 24 eyes (34.2%) of retinal-vitreous surgery. The length of hospital stay was shortened in phacomulsification/IOL after clinical pathway implemenation: 7.8 +/- 3.3 to 6.7 +/- 2.5 (mean +/- standard deviation) days. Glaucoma patients had a significantly shorter stay, from 16.4 +/- 5.0 to 12.6 +/- 3.3 days Mann-Whitney U test ; p = 0.032), and the hospital tay for retinal-vitreous surgery was shortened rom 22.8 +/- 11.1 to 17.9 +/- 6.2 days (p = 0.001). CONCLUSIONS: The application of clinical pathways resulted in substantially reduced hospital stay.

Acute Corneal Toxicity of Combined Antiglaucoma Topical Eyedrops.

PURPOSE: To investigate the corneal toxicity of three combined antiglaucoma topical eyedrops using transepithelial electrical resistance (TER) and scanning electron microscopy (SEM). METHODS: Corneal TER changes after a 60-s exposure to latanoprost/timolol with 0.02% benzalkonium chloride (BAC), travoprost/timolol with polyquaternium-1, and dorzolamide/timolol with 0.005% BAC were measured in living rabbits. Corneal damage was also examined by SEM. Hank's balanced salt solution (HBSS) was used as a control. RESULTS: There was a significant decrease in the corneal TER after exposure of the cornea to latanoprost/timolol with 0.02% BAC. Travoprost/timolol with polyquaternium-1 and dorzolamide/timolol with 0.005% BAC did not produce any significant decrease in the corneal TER as compared to HBSS control eyes. SEM revealed that superficial cells of corneas treated with latanoprost/timolol with 0.02% BAC were damaged and exhibited degenerated microvilli. Conversely, the superficial cells of corneas exposed to travoprost/timolol with polyquaternium-1 or dorzolamide/timolol with 0.005% BAC appeared normal and had normal microvilli under SEM examinations. CONCLUSION: The corneal toxicity of latanoprost/timolol with 0.02% BAC is greater than that of travoprost/timolol with polyquaternium-1 and dorzolamide/timolol with 0.005% BAC. Latanoprost/timolol contains 0.02% BAC, which may be responsible for the corneal toxicity.

Less Invasive Corneal Transepithelial Electrical Resistance Measurement Method.

PURPOSE: To evaluate acute corneal permeability changes after instillation of benzalkonium chloride (BAC) using a newly developed in vivo less invasive corneal transepithelial electrical resistance (TER) measurement method in animals and humans. METHODS: We previously developed an in vivo method for measuring corneal TER using intraocular electrodes in animals. This method can be used to precisely measure the decline of the corneal barrier function after instillation of BAC. To lessen the invasiveness of that procedure, we further refined the method for measuring the corneal TER by developing electrodes that could be placed on the surface of the cornea and in the conjunctival sac instead of inserting them into the anterior chamber. Corneal TER changes before and after exposure to 0.02% BAC were determined in this study using the new device in both rabbits and humans. RESULTS: There was a significant decrease in the corneal TER after exposure of the cornea to 0.02% BAC solution in both rabbits and humans (P<.01). The results of this new less invasive method agreed with those of formerly established anterior chamber methods in rabbit experiments. CONCLUSION: This new less invasive corneal TER measurement method enables us for the first time to measure TER of the human cornea, allowing safe and reliable investigation of the direct effect of different eye drop treatments on the corneal epithelium.

Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs.

The main pathogenesis of intervertebral disc (IVD) herniation involves disruption of the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and the resulting prolapse of the nucleus pulposus. Owing to the avascular nature of the IVD and lack of understanding the mechanisms that maintain the IVD, current therapies do not lead to tissue regeneration. Here we show that homeobox protein Mohawk (Mkx) is a key transcription factor that regulates AF development, maintenance and regeneration. Mkx is mainly expressed in the outer AF (OAF) of humans and mice. In Mkx(-/-) mice, the OAF displays a deficiency of multiple tendon/ligament-related genes, a smaller OAF collagen fibril diameter and a more rapid progression of IVD degeneration compared with the wild type. Mesenchymal stem cells overexpressing Mkx promote functional AF regeneration in a mouse AF defect model, with abundant collagen fibril formation. Our results indicate a therapeutic strategy for AF regeneration.