Conjunctival epitheliopathy induced by topical exposure to bacterial peptidoglycan, muramyl dipeptide.

Noninfectious exudative conjunctivitis can be experimentally produced in rabbits by application of the apoptogenic bacterial cell wall peptidoglycan, muramyl dipeptide (MDP) to the ocular surface. The purpose of this study was to investigate the acute conjunctival cytopathology induced by unilateral ocular surface exposure to MDP. Hematoxylin and eosin staining assessed bilateral tear cytopathology and conjunctival histopathology. The caspases levels in conjunctival tissue and tears were measured in standard assays utilizing p-nitroanaline tagged caspase-specific substrates. Immunofluorescent antibody identified intracellular caspase-3, nuclear factor-κß (NF-κß), and oxidative DNA damage (8-OHdG; 8-oxo-2'-deoxyguanosine) in tear and conjunctiva cells. DNA extracted from conjunctival tissues and pooled tear fluids were visualized by ethydium bromide agarose gel electrophoresis. Onset of ipsilateral conjunctivitis was due to an epitheliopathy characterized by loss of conjunctival epithelial cell adherence, exuviation of conjunctival epithelial cells, and neutrophil infiltration. Caspase-3 levels were significantly higher in exuviated cells in ipsilateral than contralateral tear (p's ≤ 0.001) collected at 3-5 h post MDP. Significantly higher caspase-2, -3, -6, -8 and -9 (p's ≤ 0.03) levels were detected in ipsilateral than contralateral conjunctival tissue at 5 h. Polymeric DNA was detected in ipsilateral but not contralateral conjunctival tissue and tears. Caspase-3, NF-κß, and 8-OHdG positive neutrophils were detected in bilateral conjunctiva and tear. The caspase-3/NF-κß epithelial cells and polymeric DNA in conjunctival tissue and shedding of caspase positive cells and polymeric DNA into ipsilateral tears support MDP induction of acute programmed cell death in vivo. The results suggest that ipsilateral exudative conjunctivitis is due to acute caspase-mediated conjunctival epitheliopathy induced by topical exposure to the bacterial peptidoglycan MDP.

Donning Gloves Before Surgical Gown Eliminates Sleeve Contamination.

BACKGROUND: There are numerous studies in the literature that have recognized the importance of the glove-gown interface as a potential source of intraoperative bacterial contamination. It has been demonstrated that the methods with which one dons their surgical gown and gloves can alter the level of gown contamination. We hypothesize that donning undergloves before the surgical gown will decrease if not eliminate sleeve contamination. METHODS: We performed a comparative study to assess the differences in gown contamination between three different gown and glove donning techniques. Participants ranged in experience level from intern to attending. Each participant covered their hands with ultraviolet light disclosing lotion and then donned surgical gown and gloves with their preferred technique and with the proposed technique in a randomly assigned order. The gowns were then removed and analyzed under ultraviolet light for distance and quantity of sleeve contamination. RESULTS: The gloves-first technique demonstrated zero contamination in all samples. This is significantly less than both closed and open staff-assisted techniques (P < .0001). All samples of closed and open techniques demonstrated some level of contamination. The distance of contamination on the right sleeve is significantly greater than the left sleeve (P < .0001). DISCUSSION: The gloves-first technique demonstrates zero sleeve contamination throughout all samples, regardless of the experience level. We strongly recommend considering the use of this glove and gown donning technique as opposed to the currently accepted closed and open techniques in an effort to reduce gown contamination.

The James A. Rand Young Investigator's Award: Battling the Opioid Epidemic with Prospective Pain Threshold Measurement.

BACKGROUND: Responsible analgesic prescribing is paramount in the opioid epidemic era, yet no standardized protocol exists. We aim to (1) quantify and correlate outpatient opioid need after total knee and hip arthroplasties (TKA and THA) with preoperative objective pain pressure thresholds (PPTs) and subjective pain measures and (2) report incidence of nonsurgical opioid prescriptions 6 weeks postoperatively. METHODS: Prospectively, PPTs were measured using an algometer with a maximum force of 20 pounds in 160 consecutive patients (90 TKA and 70 THA). Two locations were tested: operative joint (medial epicondyle TKA and lateral iliac crest THA) and ipsilateral olecranon for systemic control. Visual Analog Score, Pain Severity Score, Pain Interference Score, and subjective pain threshold were obtained. Six-week outpatient narcotic consumption morphine equivalents recorded and prescriptions crosschecked with the state Controlled Substance Reporting System. Multivariate analysis was performed to evaluate local and/or systemic PPT and subjective measures with narcotic consumption. RESULTS: Average operative site and systemic PPT was 6.91 and 7.72 pounds force, respectively. Subjective averages: Visual Analog Score 7.14, Pain Severity Score 5.05, Pain Interference Score 5.16, and perceived threshold 6.77. Six-week average outpatient narcotic consumption was 314.9 morphine equivalents or 125 five milligram oxycodones. Twenty percent received opioids from outside providers. Linear regression revealed a negative correlation between operative site PPT (-0.26; P = .047) and systemic PPT (-0.31; P = .021). Subjective pain metrics failed to meet significance. CONCLUSION: This novel study demonstrated a statistically significant negative correlation between preoperative pain threshold and outpatient narcotic consumption. Twenty percent of patients received opioid prescriptions outside orthopedic providers in the 6 weeks after surgery highlighting the importance of interdisciplinary communication.

Survey response rates in health sciences education research: A 10-year meta-analysis.

Growth in the online survey market may be increasing response burden and possibly jeopardizing higher response rates. This meta-analysis evaluated survey trends over one decade (2011-2020) to determine: (1) changes in survey publication rates over time, (2) changes in response rates over time, (3) typical response rates within health sciences education research, (4) the factors influencing survey completion levels, and (5) common gaps in survey methods and outcomes reporting. Study I estimated survey publication trends between 2011 and 2020 using articles published in the top three health sciences education research journals. Study II searched the anatomical sciences education literature across six databases and extracted study/survey features and survey response rates. Time plots and a proportional meta-analysis were performed. Per 2926 research articles, the annual estimated proportion of studies with survey methodologies has remained constant, with no linear trend (p > 0.050) over time (Study I). Study II reported a pooled absolute response rate of 67% (95% CI = 63.9-69.0) across 360 studies (k), totaling 115,526 distributed surveys. Despite response rate oscillations over time, no significant linear trend (p = 0.995) was detected. Neither survey length, incentives, sponsorship, nor population type affected absolute response rates (p ≥ 0.070). Only 35% (120 of 339) of studies utilizing a Likert scale reported evidence of survey validity. Survey response rates and the prevalence of studies with survey methodologies have remained stable with no linear trends over time. We recommend researchers strive for a typical absolute response rate of 67% or higher and clearly document evidence of survey validity for empirical studies.

Biomechanical performance of a new device for medial malleolar fractures.

BACKGROUND: Displaced medial malleolus fractures require surgical repair because of the critical role the structure plays in normal joint function. Various approaches exist, but options are limited for small fragment fractures. This study compared repair with the Medial Malleolar Sled fixation system (Trimed, Inc, Valencia, CA) to lag screws in 2 modes of biomechanical loading in a cadaveric model. METHODS: A Müller type B medial malleolus fracture was simulated on matched pairs of cadaveric lower extremities and repaired with the sled or 2 cancellous lag screws. Tibial distraction (tension, n = 10) or internal rotation (torsion, n = 11) was applied. Fragment movement was measured in the sagittal (tension and torsion) and transverse (torsion-only) planes. Fragment movement at 1 mm and 2 mm (clinical malunion) of gapping during tension and at 2, 4, 6, and 8 N-m during torsion was analyzed via paired t tests. RESULTS: In tension, the load at the 2-mm gap was statistically lower for screws (P = .026). Opening angle was statistically larger for the sled at the 1-mm (P = .0004) and 2-mm (P = .008) gap. In torsion, gapping was statistically lower for the sled (ranging from P = .0013 at 4 N-m to P = .0187 at 8 N-m). No differences were detected for opening angle or transverse plane movement. CONCLUSION: The sled appeared stronger in tension and as effective as lag screws in torsion. The sled may be a viable option for fractures too small for 4.0- or 3.5-mm lag screws. CLINICAL RELEVANCE: The sled may be suitable in applications where a tension band would normally be considered and may provide stronger fixation in osteoporotic bone compared with lag screw fixation.

Bilateral ptosis/blepharitis due to lepromatous leprosy.

PURPOSE: To underscore the importance of histopathological evaluation in cases presenting with a constellation of unusual ocular inflammation and physical findings. OBSERVATION: A 51-year-old male, presented with a chief complaint of worsening visual field loss due to droopy eyelids two months post excision of a right upper eyelid squamous cell carcinoma. His past medical history included chronic edematous facial features, chronic sinusitis, unexplained peripheral neuropathy, and worsening fatigue. Pre-blepharoplasty work-up revealed mechanical ptosis from lid edema, madarosis, a concave nasal bridge, pancytopenia, and numerous burn marks due to inadvertent injuries. Bilateral blepharoplasty was performed, and the excised tissue submitted for histopathological evaluation that revealed non-caseating granulomatous perineural inflammation with numerous acid-fast bacilli in dermal layers and nerves. These findings prompted a diagnosis of lepromatous leprosy with suspected bone marrow involvement. The source of the infection was unknown. The blepharoplasty restored his visual fields and multi-drug therapy (MDT) improved his general health and wellbeing with concomitant reductions of pancytopenia, fatigue, and facial edema. CONCLUSIONS AND IMPORTANCE: Biopsy histopathology, in patients with longstanding ocular adnexal inflammation, can facilitate diagnosis and treatment. To the authors' knowledge, this is an unusual ocular leprosy presentation and represents the first leprosy case diagnosed via blepharoplasty.

The effects of phylogeny, body size, and locomotor behavior on the three-dimensional shape of the pelvis in extant carnivorans.

The mammalian pelvis is thought to exhibit adaptations to the functional demands of locomotor behaviors. Previous work in primates has identified form-function relationships between pelvic shape and locomotor behavior; few studies have documented such relationships in carnivorans, instead focusing on long bones. Most work on the functional morphology of the carnivoran pelvis, in particular, has used univariate measures, with only a few previous studies incorporating a three-dimensional (3D) analysis. Here we test the hypothesis that carnivoran taxa that are characterized by different locomotor modes also differ in 3D shape of the os coxae. Using 3D geometric morphometrics and phylogenetic comparative methods, we evaluate the phylogenetic, functional, and size-related effects on 3D pelvis shape in a sample of 33 species of carnivorans. Using surface models derived from laser scans, we collected a suite of landmarks (N = 24) and curve semilandmarks (N = 147). Principal component analysis on Procrustes coordinates demonstrates patterns of shape change in the ischiopubis and ilium likely related to allometry. Phylogenetic generalized least squares analysis on principal component scores demonstrates that phylogeny and body size have greater effects on pelvic shape than locomotor function. Our results corroborate recent research finding little evidence of locomotor specialization in the pelvis of carnivorans. More research on pelvic morphological integration and evolvability is necessary to understand the factors driving pelvic evolution in carnivorans.

Orbital metastasis of keratinizing squamous cell cervical carcinoma with giant cells. A case report.

A case of orbital metastasis of cervical keratinizing squamous cell carcinoma is presented. The patient, in remission from primary cervical and ovarian cancers, presented with complaints of left eye ptosis and pain. Examination revealed the presence of a moderately tender mass along the left supra-temporal orbital rim and downward displacement of the left globe. Computed tomography revealed a poorly circumscribed mass with superior lateral wall bone loss. Excised tissue contained invasive, poorly differentiated nests of pan keratin and epithelial membrane antigen-positive squamous cells with numerous pleomorphic multinucleated giant cells. Multiple treatment regimes were unsuccessful, and the patient expired due to disease complications after 3 months.

A Review of FOXI3 Regulation of Development and Possible Roles in Cancer Progression and Metastasis.

Development and cancer share a variety of functional traits such as EMT, cell migration, angiogenesis, and tissue remodeling. In addition, many cellular signaling pathways are noted to coordinate developmental processes and facilitate aspects of tumor progression. The Forkhead box superfamily of transcription factors consists of a highly conserved DNA binding domain, which binds to specific DNA sequences and play significant roles during adult tissue homoeostasis and embryogenesis including development, differentiation, metabolism, proliferation, apoptosis, migration, and invasion. Interestingly, various studies have implicated the role of key Fox family members such as FOXP, FOXO, and FOXA during cancer initiation and metastases. FOXI3, a member of the Forkhead family affects embryogenesis, development, and bone remodeling; however, no studies have reported a role in cancer. In this review, we summarize the role of FOXI3 in embryogenesis and bone development and discuss its potential involvement in cancer progression with a focus on the bone metastasis. Moreover, we hypothesize possible mechanisms underlying the role of FOXI3 in the development of solid tumor bone metastasis.

Influence of Trainee Experience on Choice of Orthopaedic Subspecialty Fellowship.

INTRODUCTION: Most orthopaedic surgery residents elect to pursue additional subspecialty training; however, factors influencing the choice of subspecialty and the ways that these factors change during training are not well understood. The aim of this investigation was to determine, on the basis of a trainee's postgraduate year (PGY), whether variability exists in factors valued when choosing a specific subspecialty. METHODS: We emailed an online survey (intended for distribution to current trainees) to a list of orthopaedic surgery residency program coordinators in the United States. The survey queried demographic information, PGY level, and the importance of 14 discrete factors in the selection of fellowship specialty according to a Likert scale rating from 1 to 4. RESULTS: There were 359 respondents representing an even distribution of PGY levels. Junior trainees assigned greater relative value to geographic location, on-call responsibilities, financial compensation, and the tradition of the residency program, whereas senior trainees assigned greater relative value to variety of cases and intellectual stimulation (all P < 0.05). DISCUSSION: The differences seen in factors valued based on trainee experience may highlight the relative importance of greater exposure to the breadth of orthopaedic surgical practice during training and increasing awareness of clinical competencies and responsibilities. CONCLUSIONS: When deciding on orthopaedic subspecialty choice, junior trainees value lifestyle factors relatively more than do senior trainees, whereas senior trainees value case variety and stimulation relatively more than junior trainees do.

Trigeminal hypertrophic interstitial neuropathy presenting as unilateral proptosis, ptosis, tearing, and facial neuralgia.

PURPOSE: To show the utility of MRI and histology in diagnosing rare cases of trigeminal hypertrophic interstitial neuropathy (HIN). OBSERVATIONS: A 57-year-old African-American woman presented with a 4-year history of right eye proptosis with tearing, headaches, and worsening right-sided trigeminal neuralgia symptoms and jaw pain. HIV and diabetes tests were negative and thyroid function was normal. MRI identified abnormal thickening of all trigeminal nerve divisions and proptosis secondary to right trigeminal nerve V1 division enlargement. The excised tissue contained S-100 positive Schwann cells in an onion-bulb pattern. Headaches resolved, but proptosis and mild trigeminal neuralgia remained 1 year post-surgery. CONCLUSIONS AND IMPORTANCE: Trigeminal HIN is very rare, but presents as chronic progressive ocular symptoms with trigeminal neuralgia. Trigeminal nerve hypertrophy is identified by MRI and confirmed histopathologically by detection of Schwann cells in an onion bulb formation.

Factors Influencing Orthopedic Surgery Residents' Choice of Subspecialty Fellowship.

In the setting of increasing student debt, a rapidly changing health care system, and growing transparency in the age of outcome reporting, residents have many factors to consider when determining which fellowship to pursue. An institutional review board-approved link to an online survey was emailed to orthopedic surgery trainees across the United States. Demographics were collected, and 14 fellowship influences were assessed using a Likert scale. A total of 360 responses were received. Of the respondents, 85.5% (n=308) were male and 14.5% (n=52) were female. Responses were received from every region of the United States and from every postgraduate year. Respondents represented the gamut of relationship status and indebtedness. Respondents were interested in all of the current major subspecialties. Pursuit of an intellectually stimulating subspecialty had the highest average Likert score (3.38), followed by variety of cases (3.26). The lowest scores were for residency program with a strong tradition of placing into a particular subspecialty (2.08) and potential to conduct research in that subspecialty (2.09). Marital status, number of children, and level of debt did not significantly affect the importance of factors in selecting a fellowship. Choice of subspecialty did influence the level of importance of various factors. Intellectual stimulation and a strong mentor were the most influential factors in the decision to pursue a given fellowship. Because fellowship is now the norm, it is important to understand the motives behind young orthopedic surgeons' career aspirations. [Orthopedics. 2017; 40(5):e820-e824.].

Orbital sporadic Burkitt lymphoma in an adult diabetic African American female and a review of adult orbital cases.

A case of sporadic Burkitt lymphoma (sBL) presenting with jaw and lid involvement in a diabetic adult African American female and a review of adult orbital Burkitt lymphoma cases are presented. Lid edema, visual loss, ophthalmoparesis, proptosis, and sinusitis progressed over 4 weeks despite antibiotic and steroid treatment. Upper lid biopsy histopathological evaluation and immunophenotyping revealed a homogenous mass of atypical CD10 and CD20-negative B-cells and tingible body macrophages yielding a "starry sky" appearance. Cytogenetic analysis detected a minor variant c-MYC translocation, but no Epstein-Barr virus RNA. Detection of multiple lesions prompted a diagnosis of stage IV disease that totally regressed following radiation and chemotherapy. Review results of the six adult orbital sBL cases support a poor prognosis and a heightened suspicion of variant CD10, CD20 and BCL6 positive sBL in adults presenting with jaw pain and rapidly progressive orbital symptoms, particularly in female, African American, and diabetic patients.