Opioid Use After Orbital, Eyelid, or Lacrimal Surgery.

PURPOSE: Opioids may be indicated to mitigate pain after oculofacial surgery. The opioid crisis prompted attention to how these medications are dispensed and disposed. This study aims to characterize opioid usage and handling of patients undergoing oculofacial plastic surgery. METHODS: Eighty-nine adult patients were surveyed on their opioid usage after undergoing orbital, lacrimal, or eyelid (including esthetic) surgery at a tertiary oculofacial plastic surgery practice. Each patient was prescribed 10 tablets of hydrocodone/acetaminophen 5 mg/325 mg; one tablet taken orally as needed every 6 hours for pain not relieved by acetaminophen. Subset analysis was performed for type of surgery, age, and gender. RESULTS: Patients consumed an average of 3 ± 0.4 tablets. In the subsets, the averages were 2.1 ± 0.5 (n = 38) tablets after eyelid surgery, 1.6 ± 0.6 (n = 24) after lacrimal surgery, and 5.6 ± 0.9 (n = 27) after orbital surgery. Greater opioid usage was observed after orbital versus eyelid surgery (p = 0.0007) and orbital versus lacrimal surgery (p = 0.0005) but not eyelid versus lacrimal surgery (p = 0.8604). Forty-six patients (51.7%) used no opioids. Over half (57.3%; n = 51) filled their prescription. Thirty-three patients (37.1%) had unused medications, of which 21 patients did not properly dispose of their medications. The mean age of patients who used opioids was less than the mean age of those who needed no opioids (p = 0.024). There were no gender differences in opioid usage use versus not (p = 0.62). CONCLUSIONS: Opioid needs after oculofacial plastic surgeries, especially eyelid and lacrimal, were minimal in this cohort. For most patients, the prescription exceeded needs. Younger age but not gender was associated with opioid use versus not. Most did not properly discard these medications. Quality improvement in both the dispensing and disposal of opioids in oculofacial surgical practice may be warranted.

Can Pediatric Endoscopists Accurately Assess Their Clinical Competency? A Comparison Across Skill Levels.

BACKGROUND: Assessment is critical to support pediatric endoscopy training. Although trainee engagement in assessment is encouraged, the use of self-assessment and its accuracy among pediatric endoscopists is not well described. We aimed to determine the self-assessment accuracy of novice, intermediate, and experienced pediatric endoscopists. METHODS: Novice (performed <50 previous colonoscopies), intermediate (50-500), and experienced (>1000) pediatric endoscopists from 3 North American academic teaching hospitals each performed a clinical colonoscopy. Endoscopists were assessed in real-time by 2 experienced endoscopists using the Gastrointestinal Endoscopy Competency Assessment Tool for Pediatric Colonoscopy (GiECATKIDS). In addition, participants self-assessed their performance using the same instrument. Self-assessment accuracy between the externally assessed and self-assessed scores was evaluated using absolute difference scores, intraclass correlation coefficients, and Bland-Altman analyses. RESULTS: Forty-seven endoscopists participated (21 novices, 16 intermediates, and 10 experienced). Overall, there was moderate agreement of externally assessed and self-assessed GiECATKIDS total scores with an intraclass correlation coefficient of 0.72 (95% confidence interval, 0.55-0.83). The absolute difference scores among the 3 groups were significantly different (P = 0.005), with experienced endoscopists demonstrating a more accurate self-assessment compared to novices (P = 0.003). Bland-Altman plots revealed that novice endoscopists' self-assessed scores tended to be higher than their externally assessed scores, indicating they overestimated their performance. CONCLUSIONS: We found that endoscopic experience was positively associated with self-assessment accuracy among pediatric endoscopists. Novices were inaccurate in assessing their endoscopic competence and were prone to overestimation of their performances. Our findings suggest novices may benefit from targeted interventions aimed at improving their insight and self-awareness.

A prospective comparison of live and video-based assessments of colonoscopy performance.

BACKGROUND AND AIMS: Colonoscopy performance is typically assessed by a supervisor in the clinical setting. There are limitations of this approach, however, because it allows for rater bias and increases supervisor workload demand during the procedure. Video-based assessment of recorded procedures has been proposed as a complementary means by which to assess colonoscopy performance. This study sought to investigate the reliability, validity, and feasibility of video-based assessments of competence in performing colonoscopy compared with live assessment. METHODS: Novice (<50 previous colonoscopies), intermediate (50-500), and experienced (>1000) endoscopists from 5 hospitals participated. Two views of each colonoscopy were videotaped: an endoscopic (intraluminal) view and a recording of the endoscopist's hand movements. Recorded procedures were independently assessed by 2 blinded experts using the Gastrointestinal Endoscopy Competency Assessment Tool (GiECAT), a validated procedure-specific assessment tool comprising a global rating scale (GRS) and checklist (CL). Live ratings were conducted by a non-blinded expert endoscopist. Outcomes included agreement between live and blinded video-based ratings of clinical colonoscopies, intra-rater reliability, inter-rater reliability and discriminative validity of video-based assessments, and perceived ease of assessment. RESULTS: Forty endoscopists participated (20 novices, 10 intermediates, and 10 experienced). There was good agreement between the live and video-based ratings (total, intra-class correlation [ICC] = 0.847; GRS, ICC = 0.868; CL, ICC = 0.749). Intra-rater reliability was excellent (total, ICC = 0.99; GRS, ICC = 0.99; CL, ICC = 0.98). Inter-rater reliability between the 2 blinded video-based raters was high (total, ICC = 0.91; GRS, ICC = 0.918; CL, ICC = 0.862). GiECAT total, GRS, and CL scores differed significantly among novice, intermediate, and experienced endoscopists (P < .001). Video-based assessments were perceived as "fairly easy," although live assessments were rated as significantly easier (P < .001). CONCLUSIONS: Video-based assessments of colonoscopy procedures using the GiECAT have strong evidence of reliability and validity. In addition, assessments using videos were feasible, although live assessments were easier.

Impact of experience on self-assessment accuracy of clinical colonoscopy competence.

BACKGROUND AND AIMS: Self-assessment is important for life-long learning and a recommended assessment method for endoscopy skills. Prior literature has not investigated self-assessment accuracy of colonoscopic competence in the clinical setting. This study aimed to determine the self-assessment accuracy of novice, intermediate, and experienced endoscopists. METHODS: Novice (performed <50 previous colonoscopies), intermediate (50-500), and experienced (>1000) endoscopists from 5 hospitals each performed a clinical colonoscopy. Video recordings of procedures were independently assessed by 2 blinded expert endoscopists by using the Gastrointestinal Endoscopy Competency Assessment Tool (GiECAT). Externally assessed and self-assessed GiECAT scores were defined as the mean of the 2 video-based ratings and as participants' own assigned ratings, respectively. Self-assessment accuracy between the externally assessed and self-assessed scores was evaluated by using absolute difference scores, intraclass correlation coefficients, and the Bland-Altman analysis. RESULTS: Twenty novice, 10 intermediate, and 10 experienced endoscopists participated. There was moderate agreement of externally assessed and self-assessed GiECAT scores, with an intraclass correlation coefficient of 0.65 (95% confidence interval, 0.44-0.80). The absolute difference scores among the 3 groups were significantly different (P = .002), with experienced endoscopists demonstrating a more accurate self-assessment ability compared with novices (P = .002). Bland-Altman plots suggest that novice and experienced endoscopists tend to overrate and underrate their clinical competence, respectively; no specific trends were associated with intermediates. CONCLUSION: Participants demonstrated moderate self-assessment accuracy of clinical competence. Endoscopist experience was positively associated with self-assessment accuracy; novices demonstrated lower self-assessment accuracy compared with experienced endoscopists. Moreover, novices tended to overestimate their performances. Novice endoscopists may benefit from targeted interventions to improve self-assessment accuracy.

Progressive learning in endoscopy simulation training improves clinical performance: a blinded randomized trial.

BACKGROUND AND AIMS: A structured comprehensive curriculum (SCC) that uses simulation-based training (SBT) can improve clinical colonoscopy performance. This curriculum may be enhanced through the application of progressive learning, a training strategy centered on incrementally challenging learners. We aimed to determine whether a progressive learning-based curriculum (PLC) would lead to superior clinical performance compared with an SCC. METHODS: This was a single-blinded randomized controlled trial conducted at a single academic center. Thirty-seven novice endoscopists were recruited and randomized to either a PLC (n = 18) or to an SCC (n = 19). The PLC comprised 6 hours of SBT, which progressed in complexity and difficulty. The SCC included 6 hours of SBT, with cases of random order of difficulty. Both groups received expert feedback and 4 hours of didactic teaching. Participants were assessed at baseline, immediately after training, and 4 to 6 weeks after training. The primary outcome was participants' performance during their first 2 clinical colonoscopies, as assessed by using the Joint Advisory Group Direct Observation of Procedural Skills assessment tool (JAG DOPS). Secondary outcomes were differences in endoscopic knowledge, technical and communication skills, and global performance in the simulated setting. RESULTS: The PLC group outperformed the SCC group during first and second clinical colonoscopies, measured by JAG DOPS (P < .001). Additionally, the PLC group had superior technical and communication skills and global performance in the simulated setting (P < .05). There were no differences between groups in endoscopic knowledge (P > .05). CONCLUSIONS: Our findings demonstrate the superiority of a PLC for endoscopic simulation, compared with an SCC. Challenging trainees progressively is a simple, theory-based approach to simulation whereby the performance of clinical colonoscopies can be improved. (Clinical trial registration number: NCT02000180.).

Palonosetron and hydroxyzine pre-treatment reduces the objective signs of experimentally-induced acute opioid withdrawal in humans: a double-blinded, randomized, placebo-controlled crossover study.

BACKGROUND: Treatments for reducing opioid withdrawal are limited and prone to problematic side effects. Laboratory studies, clinical observations, and limited human trial data suggest 5-HT3-receptor antagonists and antihistamines may be effective. OBJECTIVES: This double-blind, crossover, placebo-controlled study employing an acute physical dependence model evaluated whether (i) treatment with a 5-HT3-receptor antagonist (palonosetron) would reduce opioid withdrawal symptoms, and (ii) co-administration of an antihistamine (hydroxyzine) would enhance any treatment effect. METHODS: At timepoint T = 0, healthy (non-opioid dependent, non-substance abuser) male volunteers (N = 10) were pre-treated with either a) placebo, b) palonosetron IV (0.75 mg), or c) palonosetron IV (0.75 mg) and hydroxyzine PO (100 mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10 mg/70kg). At T = 165, 10 mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. RESULTS: Comparison of average baseline OOWS scores with OOWS scores obtained 15 minutes after naloxone was significant (p = 0.0001). Scores from 15 minutes post-naloxone infusion showed significant differences in OOWS scores between treatment groups: placebo, 3.7 ± 2.4; palonosetron, 1.5 ± 0.97; and palonosetron with hydroxyzine, 0.2 ± 0.1333. CONCLUSIONS: Pretreatment with palonosetron significantly reduced many signs of experimentally-induced opioid withdrawal. Co-administration with hydroxyzine further reduced opioid withdrawal severity. These results suggest that 5-HT3 receptor antagonists, alone or in combination with an antihistamine, may be useful in the treatment of opioid withdrawal.

Impact of a simulation training curriculum on technical and nontechnical skills in colonoscopy: a randomized trial.

BACKGROUND: GI endoscopy simulation-based training augments early clinical performance; however, the optimal manner by which to deliver training is unknown. OBJECTIVE: We aimed to validate a simulation-based structured comprehensive curriculum (SCC) designed to teach technical, cognitive, and integrative competencies in colonoscopy. DESIGN: Single-blinded, randomized, controlled trial. SETTING: Endoscopic simulation course at an academic hospital. PARTICIPANTS AND INTERVENTIONS: Thirty-three novice endoscopists were allocated to an SCC group or self-regulated learning (SRL) group. The SCC group received a curriculum consisting of 6 hours of didactic lectures and 8 hours of virtual reality simulation-based training with expert feedback. The SRL group was provided a list of desired objectives and was instructed to practice on the simulator for an equivalent time (8 hours). MAIN OUTCOME MEASUREMENTS: Clinical transfer was assessed during 2 patient colonoscopies using the Joint Advisory Group Direct Observation of Procedural Skills (JAG DOPS) scale. Secondary outcome measures included differences in procedural knowledge, immediate post-training simulation performance, and delayed post-training (4-6 weeks) performance during an integrated scenario test on the JAG DOPS communication and integrated scenario global rating scales. RESULTS: There was no significant difference in baseline or post-training performance on the simulator task. The SCC group performed superiorly during their first and second clinical colonoscopies. Additionally, the SCC group demonstrated significantly better knowledge and colonoscopy-specific performance, communication, and global performance during the integrated scenario. LIMITATIONS: We were unable to measure SRL participants' effort outside of mandatory training. In addition, feedback metrics and number of available simulation cases are limited. CONCLUSIONS: These results support integration of endoscopy simulation into a structured curriculum incorporating instructional feedback and complementary didactic knowledge as a means to augment technical, cognitive, and integrative skills acquisition, as compared with SRL on virtual reality simulators. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01991522.)

Gastrointestinal Endoscopy Competency Assessment Tool: reliability and validity evidence.

BACKGROUND: Rigorously developed and validated direct observational assessment tools are required to support competency-based colonoscopy training to facilitate skill acquisition, optimize learning, and ensure readiness for unsupervised practice. OBJECTIVE: To examine reliability and validity evidence of the Gastrointestinal Endoscopy Competency Assessment Tool (GiECAT) for colonoscopy for use within the clinical setting. DESIGN: Prospective, observational, multicenter validation study. Sixty-one endoscopists performing 116 colonoscopies were assessed using the GiECAT, which consists of a 7-item global rating scale (GRS) and 19-item checklist (CL). A second rater assessed procedures to determine interrater reliability by using intraclass correlation coefficients (ICCs). Endoscopists' first and second procedure scores were compared to determine test-retest reliability by using ICCs. Discriminative validity was examined by comparing novice, intermediate, and experienced endoscopists' scores. Concurrent validity was measured by correlating scores with colonoscopy experience, cecal and terminal ileal intubation rates, and physician global assessment. SETTING: A total of 116 colonoscopies performed by 33 novice (<50 previous procedures), 18 intermediate (50-500 previous procedures), and 10 experienced (>1000 previous procedures) endoscopists from 6 Canadian hospitals. MAIN OUTCOME MEASUREMENTS: Interrater and test-retest reliability, discriminative, and concurrent validity. RESULTS: Interrater reliability was high (total: ICC=0.85; GRS: ICC=0.85; CL: ICC=0.81). Test-retest reliability was excellent (total: ICC=0.91; GRS: ICC=0.93; CL: ICC=0.80). Significant differences in GiECAT scores among novice, intermediate, and experienced endoscopists were noted (P<.001). There was a significant positive correlation (P<.001) between scores and number of previous colonoscopies (total: ρ=0.78, GRS: ρ=0.80, CL: Spearman's ρ=0.71); cecal intubation rate (total: ρ=0.81, GRS: Spearman's ρ=0.82, CL: Spearman's ρ=0.75); ileal intubation rate (total: Spearman's ρ=0.82, GRS: Spearman's ρ=0.82, CL: Spearman's ρ=0.77); and physician global assessment (total: Spearman's ρ=0.90, GRS: Spearman's ρ=0.94, CL: Spearman's ρ=0.77). LIMITATIONS: Nonblinded assessments. CONCLUSION: This study provides evidence supporting the reliability and validity of the GiECAT for use in assessing the performance of live colonoscopies in the clinical setting.

The gastrointestinal endoscopy competency assessment tool for pediatric colonoscopy.

OBJECTIVES: Validated assessment tools are required to support competency-based education. We aimed to assess the reliability and validity of the Gastrointestinal Endoscopy Competency Assessment Tool for Pediatric Colonoscopy (GiECATKIDS), an instrument developed by 41 North American experts using Delphi methodology. METHODS: GiECATKIDS consists of a 7-item global rating scale (GRS) and an 18-item checklist (CL). An attending physician assessed 104 colonoscopies performed at 3 North American hospitals by 56 endoscopists, including 25 novices (<50 previous procedures), 21 intermediates (50-250), and 10 advanced endoscopists (>500). Another observer rated procedures to assess interrater reliability using intraclass correlation coefficient (ICC). Test-retest reliability was measured with ICC comparing endoscopists' first and second procedure scores. Discriminative validity was examined by comparing experience level with scores. Concurrent validity was assessed by correlating scores with colonoscopy experience, cecal and terminal ileal intubation rates, and physician global assessment. RESULTS: Interrater reliability of the GiECATKIDS was high (total: ICC = 0.88; GRS: ICC = 0.79; CL: ICC = 0.89). Test-retest reliability was excellent (total: ICC = 0.94; GRS: ICC = 0.94; CL: ICC = 0.84). GiECATKIDS total, GRS, and CL scores differed significantly among novice, intermediate, and advanced endoscopists (P < 0.001). There was a significant positive correlation (P < 0.001) between scores and number of previous colonoscopies (total: ρ = 0.91, GRS: ρ = 0.92, CL: ρ = 0.84), cecal intubation rate (total: ρ = 0.82, GRS: ρ = 0.85, CL: ρ = 0.77), ileal intubation rate (total: ρ = 0.82, GRS: ρ = 0.82, CL: ρ = 0.80), and physician global assessment (total: ρ = 0.95, GRS: ρ = 0.94, CL: ρ = 0.89). CONCLUSIONS: The GiECATKIDS demonstrates strong reliability and validity as a measure of performance of pediatric colonoscopy that can be used to support training and assessment.

DEXAMETHASONE INTRAVITREAL IMPLANT COMPLICATIONS INCLUDING VITREOUS HEMORRHAGE AND HYPOTONY.

PURPOSE: To describe cases of visually significant vitreous hemorrhage (VH) following dexamethasone intravitreal implant in our practice and present two cases that required surgical intervention and a case of VH and hypotony following dexamethasone implant. An injection technique that may minimize the incidence of these complications is described and illustrated. METHODS: Retrospective case series. RESULTS: The overall incidence of VH was 1.7% (8 of 467 injections) and those that required surgical intervention was 0.4% (2/467) over a 10-year period, from June 2010 to June 2020 ( Table 1 ). Overall, 75% (6 of 8) VH resolved spontaneously over time, without surgical intervention. CONCLUSION: Nonclearing VH and hypotony are rare but serious complications of dexamethasone implant.

Severe Multifocal Placoid Chorioretinitis Associated with Immune Checkpoint Inhibitor Therapy.

PURPOSE: To report a case of severe bilateral multifocal placoid chorioretinitis in a patient receiving ipilimumab and nivolumab therapy for metastatic melanoma. METHODS: Retrospective, observational case report. RESULTS: A 31-year-old woman on ipilimumab and nivolumab for metastatic melanoma developed severe multifocal placoid chorioretinitis in both eyes. The patient was started on topical and systemic corticosteroid therapy and immune checkpoint inhibitor therapy was paused. Following resolution of ocular inflammation, the patient was restarted on immune checkpoint inhibitor therapy without return of ocular symptoms. CONCLUSION: Extensive multifocal placoid chorioretinitis may occur in patients undergoing immune checkpoint inhibitor (ICPI) therapy. Some patients with ICPI-related uveitis may successfully resume ICPI therapy under close collaboration with the treating oncologist.

RELAXING NASAL RETINOTOMY TECHNIQUE FOR CLOSURE OF A MACULAR HOLE THAT REOPENED AFTER PRIMARY VITRECTOMY.

PURPOSE: To describe relaxing nasal retinotomy as a technique to achieve closure of a recurrent macular hole. METHODS: A patient with juxtafoveal telangiectasia presented with recurrent macular hole after primary vitrectomy and internal limiting membrane peel. During repeat surgery, a superonasal retinotomy was performed to allow for release of tangential traction contributing to the macular hole. RESULTS: Intraoperative ocular coherence tomography demonstrated decrease in size of the macular hole immediately after retinotomy. At follow-up, both the macular hole and retinotomy site had closed completely. CONCLUSION: In patients with small macular holes that fail primary vitrectomy, nasal relaxing retinotomy can contribute to successful hole closure.

Age-Related Macular Degeneration (AMD) Transmitochondrial Cybrids Protected from Cellular Damage and Death by Human Retinal Progenitor Cells (hRPCs).

PURPOSE: One of the leading causes of irreversible blindness worldwide, age-related macular degeneration (AMD) is a progressive disorder leading to retinal degeneration. While several treatment options exist for the exudative form of AMD, there are currently no FDA-approved treatments for the more common nonexudative (atrophic) form. Mounting evidence suggests that mitochondrial damage and retinal pigment epithelium (RPE) cell death are linked to the pathogenesis of AMD. Human retinal progenitor cells (hRPCs) have been studied as a potential restorative therapy for degenerative conditions of the retina; however, the effects of hRPC treatment on retinal cell survival in AMD have not been elucidated. METHODS: In this study, we used a cell coculture system consisting of hRPCs and AMD or age-matched normal cybrid cells to characterize the effects of hRPCs in protecting AMD cybrids from cellular and mitochondrial damage and death. RESULTS: AMD cybrids cocultured with hRPCs showed (1) increased cell viability; (2) decreased gene expression related to apoptosis, autophagy, endoplasmic reticulum (ER) stress, and antioxidant pathways; and (3) downregulation of mitochondrial replication genes compared to AMD cybrids without hRPC treatment. Furthermore, hRPCs cocultured with AMD cybrids showed upregulation of (1) neuronal and glial markers, as well as (2) putative neuroprotective factors, responses not found when hRPCs were cocultured with age-matched normal cybrids. CONCLUSION: The current study provides the first evidence that therapeutic benefits may be obtainable using a progenitor cell-based approach for atrophic AMD. Our results suggest that bidirectional interactions exist between hRPCs and AMD cybrids such that hRPCs release trophic factors that protect the cybrids against the cellular and mitochondrial changes involved in AMD pathogenesis while, conversely, AMD cybrids upregulate the release of these neuroprotective factors by hRPCs while promoting hRPC differentiation. These in vitro data provide evidence that hRPCs may have therapeutic potential in atrophic AMD.

Signal Strength Reduction Effects in OCT Angiography.

PURPOSE: To elucidate the relationship between vessel density (VD) measurements and signal strength in OCT angiography (OCTA). DESIGN: Cross-sectional study. PARTICIPANTS: Healthy volunteers. METHODS: OCT angiography images obtained from healthy volunteers were analyzed to demonstrate the relationship between signal strength index (SSI) and VD. Experiments were performed to determine the effects of signal strength reduction on VD measurements on the Optovue/AngioVue (Optovue, Inc, Fremont, CA) and Cirrus/AngioPlex OCTA (Carl Zeiss Meditec, Inc, Dublin, CA) systems. Signal strength reduction was generated by either neutral density filters (NDFs) or defocus. MAIN OUTCOME MEASURES: Regression analysis of signal strength effects on VD. RESULTS: Vessel density decreased linearly with signal strength with high statistical significance on both OCTA systems tested and for all analyzed sources of variation in signal strength. The slope of VD versus SSI was greatest when signal strength was adjusted by NDFs, followed by defocus, interscan difference, interindividual variation, and left-right eye difference. Multivariate analysis revealed that both SSI and age had a significant effect on the interindividual variation in VD. CONCLUSIONS: Vessel density measurements using OCTA were affected significantly by OCT signal strengths on 2 OCTA platforms. Investigators should exercise caution when interpreting VD data from OCTA scans. Quantification algorithms for OCTA should ideally remove the signal strength bias.

The interleukin-17 receptor plays a gender-dependent role in host protection against Porphyromonas gingivalis-induced periodontal bone loss.

Interleukin-17 (IL-17) is a proinflammatory cytokine secreted by the newly described CD4(+) Th17 subset, which is distinct from classic Th1 and Th2 lineages. IL-17 contributes to bone destruction in rheumatoid arthritis but is essential in host defense against pathogens that are susceptible to neutrophils. Periodontal disease (PD) is a chronic inflammatory condition initiated by anaerobic oral pathogens such as Porphyromonas gingivalis, and it is characterized by host-mediated alveolar bone destruction due primarily to the immune response. The role of IL-17 in PD is controversial. Whereas elevated IL-17 levels have been found in humans with severe PD, we recently reported that female C57BL/6J mice lacking the IL-17 receptor (IL-17RA(KO)) are significantly more susceptible to PD bone loss due to defects in the chemokine-neutrophil axis (J. J. Yu, M. J. Ruddy, G. C. Wong, C. Sfintescu, P. J. Baker, J. B. Smith, R. T. Evans, and S. L. Gaffen, Blood 109:3794-3802, 2007). Since different mouse strains exhibit differences in susceptibility to PD as well as Th1/Th2 cell skewing, we crossed the IL-17RA gene knockout onto the BALB/c background and observed a similar enhancement in alveolar bone loss following P. gingivalis infection. Unexpectedly, in both strains IL-17RA(KO) female mice were much more susceptible to PD bone loss than males. Moreover, female BALB/c-IL-17RA(KO) mice were defective in producing anti-P. gingivalis immunoglobulin G and the chemokines KC/Groalpha and MIP-2. In contrast, male mice produced normal levels of chemokines and anti-P. gingivalis antibodies, but they were defective in granulocyte colony-stimulating factor upregulation. This study demonstrates a gender-dependent effect of IL-17 signaling and indicates that gender differences should be taken into account in the preclinical and clinical safety testing of anti-IL-17 biologic therapies.

Interleukin-17: a novel inflammatory cytokine that bridges innate and adaptive immunity.

Interleukin-17 (IL-17A) is a pro-inflammatory cytokine that is primarily secreted from T lymphocytes, mediators of adaptive immunity. Recently, IL-17 was shown to be the defining cytokine of a new T helper subset termed "Th17." Discovery of the Th17 population was a groundbreaking discovery that has triggered major revisions of the prevailing paradigms in T cell biology. Although produced by T cells, IL-17 promotes expansion and recruitment of innate immune cells such as neutrophils, and also cooperates with TLR ligands, IL-1 beta, and TNF alpha to enhance inflammatory reactions and stimulate production of beta-defensins and other antimicrobial peptides. Its receptor, IL-17RA, is ubiquitously expressed and shares many features with classical innate immune receptors such as shared intracellular tail motifs and convergence on common inflammatory transcription pathways. The role of IL-17 in periodontal disease is still uncertain, since IL-17 has been shown to promote bone destruction in arthritis, but is nonetheless essential to protect the host from pathogens, including periodontopathic organisms. Recent evidence has shown that Th17 cells are more osteoclastogenic than other T helper subsets such as Th1 or Th2. Ablation of IL-17 signaling prior to onset of infection with Porphyromonas gingivalis increases susceptibility to periodontal bone loss, but this finding does not rule out the efficacy of therapeutic inhibition of IL-17 after onset of severe disease. IL-17 sits at the center of many complex diseases that integrate innate and adaptive immune mechanisms and requires careful study to maximize host protective effects and minimize host deleterious effects.

Insulin resistance and cognitive test performance in elderly adults: National health and nutrition examination survey (NHANES).

OBJECTIVES: To examine the relationship between homeostatic model of insulin resistance (HOMA-IR) and cognitive test performance among population≥60years in a national database. HYPOTHESIS: Higher insulin resistance is associated with lower cognitive test performance score in the population≥60years. PARTICIPANTS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2001-2002. MEASUREMENTS: Cognitive test performance was measured by the Digit Symbol Substitution (DSS) exercise score. The main independent variable was the homeostasis model assessment of insulin resistance (HOMA-IR). We used bivariate analysis and generalized linear model adjusting for age, gender, race, education, body mass index, and systolic and diastolic blood pressures; total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride levels; and physical activity, diabetes mellitus, stroke, and congestive heart failure. STATA 14 was used to analyze the data taking into consideration the design, strata and weight. RESULTS: Of the 1028 participants, 44% were male and 85% were white. The mean age was 70.0±0.28 (SE) years. Their average HOMA-IR was 3.6±0.14 and they had a mean of 49.2±0.8 correct DSS score in the cognitive test. Adjusting for the confounding variables, HOMA-IR was associated with decline in DSS score (B=-0.30, 95% confidence interval=-0.54 and -0.05, p=0.01). The model explained 44% of the variability of the DSS score (R2=0.44). Significant predictors of decline in DSS score were age, gender, race, and education (p=0.01). CONCLUSION: Insulin resistance as measured by HOMA-IR was independently associated with lower cognitive test performance score among elderly participants aged ≥60years. Longitudinal studies are needed to test the mechanism and the causal relationship.

Mitochondrial Impairment in Antibiotic Induced Toxic Optic Neuropathies.

There is growing evidence for the role of mitochondrial dysfunction in the toxic optic neuropathies. Due to the structural similarities between antibiotic targets and mitochondrial machinery, several antibiotics known to cause optic neuropathy have deleterious effects on mitochondrial function. We review the literature on the prevalence, clinical manifestations, and management of antibiotic induced toxic optic neuropathies. The effect of these antibiotics on mitochondrial function in regard to the optic nerve is discussed.

A case report on a rare anatomic variant of cystic duct insertion.

We report a case a 70-year-old female presenting with abdominal pain who has a cystic duct coursing medial to the common bile duct before anastomosing just proximal to the ampulla. Low medial insertion of the cystic duct is a rare anatomic variant that is easily misidentified on imaging studies and may complicate surgical and percutaneous intervention. It can be identified by pre-operative imaging modalities such as magnetic resonance cholangiopancreatography.