Simulation-based training for embryo transfer for clinicians with differing levels of expertise: an application of the American Society for Reproductive Medicine Embryo Transfer Simulator.

Objective: To compare the learning curve of clinicians with different levels of embryo transfer (ET) experience using the American Society for Reproductive Medicine (ASRM) Embryo Transfer Simulator. Design: Prospective cohort study. Setting: Single large university-affiliated in vitro fertilization center. Patients: Participants with 3 levels of expertise with ET were recruited: "group 1" (Reproductive Endocrinology and Infertility attendings), "group 2" (Reproductive Endocrinology and Infertility nurses, advance practice providers, or medical assistants), and "group 3" (Obstetrics and Gynecology resident physicians). Interventions: All participants completed ET simulation training using uterine cases A, B, and C (easiest to most difficult) of the ASRM ET Simulator. Participants completed each case 5 times for a total of 15 repetitions. Main Outcome Measures: The primary outcome was ET simulation scores analyzed at each attempt for each uterine case, with a maximum score of 155. Secondary outcomes included self-assessed comfort levels before and after the completion of the simulation and total duration of ET. Comfort was assessed using a 5-point Likert scale. Results: Twenty-seven participants with 3 different levels of expertise with ET were recruited from December 2020 to February 2021. For cases A and B, median total scores were not significantly different between groups 1 and 3 at first or last attempts. Group 2 did not perform as well as group 3 at the beginning of case A or group 1 at the end of case B. All groups demonstrated a decrease in total time from the first attempt to the last attempt for both cases. For case C, the "difficult" uterus, groups 2 and 3 exhibited the greatest improvement in total median score: from 0 to 75 from the first to last attempt. Group 1 scored equally well from first through last attempts. Although no one from group 2 or 3 achieved a passing score with the first attempt (80% of the max score), approximately 30% had passing scores at the last attempt. Groups 1 and 3 showed a significant decrease in total time across attempts for case C. Following simulation, 100% of groups 2 and 3 reported perceived improvement in their skills. Group 3 showed significant improvement in comfort scores with Likert scores of 1.71 ± 0.76 and 1.0 ± 0.0 for the "Easy" and "Difficult" cases, respectively, before simulation and 4.57 ± 0.53 and 2.4 ± 1.1 after simulation. Conclusions: The ASRM ET Simulator was effective in improving both technical skill and comfort level, particularly for those with little to no ET experience and was most marked when training on a difficult clinical case.

Risk Factors for Failure of Final Anatomic Surgical Reattachment in Retinal Detachments From Combat Ocular Trauma.

BACKGROUND AND OBJECTIVE: The goal of this study was to determine the anatomic outcome of traumatic retinal detachment (RD) from combat ocular trauma. MATERIALS AND METHODS: Retrospective study of patients sustaining a traumatic RD in Operation Iraqi Freedom and Operation Enduring Freedom who were evacuated to Walter Reed Army Medical Center from 2001 to 2011. The Fisher exact test, Wilcoxon rank sum test, and Agresti and Coull methods were used for analyses. RESULTS: There were 143 eyes of 134 patients in which a traumatic RD developed, of a total of 890 eyes of 652 patients in the Walter Reed Ocular Trauma Database. Based on our results, predictors for failure to reattach the retina include maculaoff status (P = .0002), open-globe injury (P = .03), proliferative vitreoretinopathy postoperatively (P = .002), and presence of hyphema (P = .02). Intraocular foreign body and time to initial retinal surgery did not increase risk for failure. Thirty-four percent (34%) of eyes failed to be reattached. CONCLUSIONS: Traumatic RD due to injury sustained in a combat zone resulted in poor prognosis, with 82.09% of eyes with RD having a best-corrected visual acuity worse than 20/200. The anatomic success of RD repair was shown to be 65.71%, likely owing to the severity of the injuries, concomitant systemic injuries, and delayed surgical intervention. [Ophthalmic Surg Lasers Imaging Retina 2022;53:493-501.].

ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY AFTER IMMUNIZATION WITH MULTIPLE VACCINES.

PURPOSE: To report a case of acute posterior multifocal placoid pigment epitheliopathy occurring in temporal association with multiple immunizations in a previously healthy 25-year-old woman. METHODS: Acute posterior multifocal placoid pigment epitheliopathy was diagnosed based on ophthalmological findings of bilateral placoid subretinal lesions complicated by a serous retinal detachment in the left eye. RESULTS: Through HLA typing, the patient was found to possess the HLA-B*40 and HLA-DB1*15 alleles. She was treated with topical prednisolone acetate 1% and monitored for several months. The serous retinal detachment resolved, and visual acuity returned to normal. CONCLUSION: This case report adds to the body of knowledge regarding possible atypical interplay between vaccines and specific T-cell receptors of the host immune system and adds Polio and Tetanus to the growing list of vaccines potentially triggering acute posterior multifocal placoid pigment epitheliopathy. Increased awareness of the presentation of acute posterior multifocal placoid pigment epitheliopathy and that it may arise after immunization may also improve evaluation of acute changes in visual acuity.

POSTERIOR SEGMENT INJURIES IN OPERATION IRAQI FREEDOM AND OPERATION ENDURING FREEDOM: 2001 to 2011.

BACKGROUND/PURPOSE: To characterize the nature of posterior segment ocular injuries in combat trauma. METHODS: Eyes in the Walter Reed Ocular Trauma Database were evaluated for the presence of posterior segment injury. Final visual outcomes in open-globe versus closed-globe injuries and by zone of injury and the types of posterior segment injuries in open-globe versus closed-globe injuries were assessed. RESULTS: Four hundred fifty-two of 890 eyes (50.8%) had at least one posterior segment injury. The mechanism of injury was most commonly an improvised explosive device in 280 (62.0%) eyes. Sixty-one patients (13.5%) had a Zone I injury, 50 (11.1%) a Zone II injury, and 341 (75.4%) a Zone III injury. Patients with Zone I injuries were more likely to have a final visual acuity of 20/200 or better compared with patients with either a Zone II (P < 0.001) or Zone III injury (P = 0.007). Eyes with a closed-globe injury were more likely to have a final visual acuity of 20/200 or better compared with those with an open-globe injury (P < 0.001). Furthermore, closed-globe injury compared with open-globe injury had a lower risk of vitreous hemorrhage (odds ratio 0.32, P < 0.001), proliferative vitreoretinopathy (odds ratio 0.14, P < 0.001), and retinal detachment (odds ratio 0.18, P < 0.001) but a higher risk of chorioretinal rupture (odds ratio 2.82, P < 0.001) and macular hole (odds ratio 3.46, P = 0.004). CONCLUSION: Patients with combat ophthalmic trauma had similar posterior segment injury patterns to civilian trauma in open-globe versus closed-globe injuries. Zone II and III injuries were associated with a worse visual prognosis.

Proliferative Vitreoretinopathy After Combat Ocular Trauma in Operation Iraqi Freedom and Operation Enduring Freedom: 2001-2011.

BACKGROUND AND OBJECTIVE: To determine the risk factors associated with developing proliferative vitreoretinopathy (PVR) from combat ocular injuries in U.S. service members. PATIENTS AND METHODS: Retrospective review of associated risk factors and outcomes of PVR within the Walter Reed Ocular Trauma Database. Ocular injuries in U.S. service members wounded during Operation Enduring Freedom and Operation Iraqi Freedom from 2001 to 2011 were assessed, and of these all cases of PVR were studied. Principal outcome measures were the risk factors associated with PVR development and rate of final visual acuity (VA) less than 20/200. RESULTS: Eight hundred ninety eyes of 651 U.S. service members were evaluated. A total of 76 eyes (8.5%) of 66 patients developed PVR. Five patients had bilateral PVR. Nineteen patients had bilateral eye injuries. Sixty-one eyes (80.2%) had a final VA less than 20/200. PVR was found to be a significant risk factor for a poor final VA (P < .001). Retinal detachment (RD) was found in 52 eyes (68.4%) of patients. In patients with a RD, intraocular foreign bodies (IOFBs) (P < .001), unsuccessful repair (P = .002), and macular hemorrhage (P = .04) were significant risk factors for the development of PVR. Time to initial retina surgery was not found to be a risk factor for PVR development (P = .5). Time to initial retina surgery was available in 41 patients and the time to surgery on average was 22.56 days (range: 3 to 87 days). CONCLUSIONS: PVR occurs frequently in combat trauma and is a significant cause of poor final VA. In patients with PVR and RD, injuries caused by an IOFB, macular hemorrhage, or unsuccessful repair were significant risk factors for the development of PVR. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:556-563.].

Intraocular Foreign Body Trauma in Operation Iraqi Freedom and Operation Enduring Freedom: 2001 to 2011.

PURPOSE: We update the incidence of intraocular foreign bodies (IOFB) in soldiers admitted to Walter Reed Army Medical Center from 2001 to 2011 after sustaining combat injuries in Operation Iraqi Freedom and Operation Enduring Freedom. DESIGN: This consecutive retrospective case series included 890 eyes of 652 patients. METHODS: Data were collected in the Walter Reed Ocular Trauma Database. Inclusion criteria were any American soldier or Department of Defense civilian with an IOFB injured in Operation Iraqi Freedom/Operation Enduring Freedom. Closed globe injuries with orbital foreign bodies, injury outside of a combat zone, or non-Department of Defense civilian trauma were the exclusion criteria. MAIN OUTCOME MEASURES: Primary outcome measures were final visual outcome and the number, size, and location of IOFBs. Secondary outcome measures included surgical procedures, use of eye protection, associated complications, source of injury and Ocular Trauma Score. RESULTS: There were 890 eye injuries in 652 patients evacuated to Walter Reed Army Medical Center between 2001 and 2011. IOFBs were found in 166 eyes of 149 patients (18.6%; 95% confidence interval [CI], 16.2%-21.3%). Most patients had a single IOFB (80.7%). An IOFB was positively associated with Ocular Trauma Score grade 1 or 2 (0-65) injuries (odds ratio [OR], 1.58; 95% CI, 1.07-2.38; P = 0.01). There were 130 eyes (78.33%) that had recorded time from initial visual acuity to final visual acuity and it ranged from 8 to 2421 days (mean, 433.24 days). Thirty-eight (25.16%; 95% CI, 18.89%-32.67%) eyes had no change in visual acuity, 98 (64.90%; 95% CI, 57.00%-72.07%) had improved visual acuity, and 15 (9.93%; 95% CI, 6.01%-15.84%) had decreased visual acuity. IOFB was not found to predict final visual acuity of <20/200 in multivariate analysis when other injury features were known (P = 0.1). Pars plana vitrectomy was completed on 124 eyes (74.70%). Removal of IOFB was performed in 118 eyes (71.08%; average of 31.67 days after initial injury) with a delayed procedure occurring after primary closure and antibiotics owing to a lack of surgical capacity in Iraq and Afghanistan. Retinal detachment occurred in 48 eyes (28.92%) and proliferative vitreoretinopathy in 44 eyes (26.5%). CONCLUSIONS: IOFBs occur frequently in combat ocular trauma and are significantly associated with more severe injuries. However, IOFBs were not found to be a significant risk factor for visual acuity of <20/200.

Case-based care for pre-existing or new-onset mood disorders in patients undergoing infertility therapy.

The inability to conceive is an immensely stressful event in a woman's life. Thus, it is no surprise that women with infertility have twice the rates of depressive symptoms as women without infertility. Incidence of depression in the general female population is approximately 20% compared to almost 40% in infertile females. Based on this information, we expect many individuals with infertility to have pre-existing mood disorders requiring ongoing treatment. In addition, we expect a subset of women to develop a mood disorder during infertility treatment due to related stressors. The reproductive endocrinology team must understand the impact of stress on pregnancy outcomes, the types of treatment options, and the safety and use of various medications. The goal of this case-based commentary is to summarize information on the relationship between stress and infertility and to offer a guide for a range of treatment options that include non-pharmacologic and pharmacologic therapies.

Kinetic-based trapping by intervening sequence variants of the active sites of protein-disulfide isomerase identifies platelet protein substrates.

Thiol isomerases such as protein-disulfide isomerase (PDI) direct disulfide rearrangements required for proper folding of nascent proteins synthesized in the endoplasmic reticulum. Identifying PDI substrates is challenging because PDI catalyzes conformational changes that cannot be easily monitored (e.g. compared with proteolytic cleavage or amino acid phosphorylation); PDI has multiple substrates; and it can catalyze either oxidation, reduction, or isomerization of substrates. Kinetic-based substrate trapping wherein the active site motif CGHC is modified to CGHA to stabilize a PDI-substrate intermediate is effective in identifying some substrates. A limitation of this approach, however, is that it captures only substrates that are reduced by PDI, whereas many substrates are oxidized by PDI. By manipulating the highly conserved -GH- residues in the CGHC active site of PDI, we created PDI variants with a slowed reaction rate toward substrates. The prolonged intermediate state allowed us to identify protein substrates that have biased affinities for either oxidation or reduction by PDI. Because extracellular PDI is critical for thrombus formation but its extracellular substrates are not known, we evaluated the ability of these bidirectional trapping PDI variants to trap proteins released from platelets and on the platelet surface. Trapped proteins were identified by mass spectroscopy. Of the trapped substrate proteins identified by mass spectroscopy, five proteins, cathepsin G, glutaredoxin-1, thioredoxin, GP1b, and fibrinogen, showed a bias for oxidation, whereas annexin V, heparanase, ERp57, kallekrein-14, serpin B6, tetranectin, and collagen VI showed a bias for reduction. These bidirectional trapping variants will enable more comprehensive identification of thiol isomerase substrates and better elucidation of their cellular functions.

Point-of-care seeding of nitinol stents with blood-derived endothelial cells.

Nitinol-based vascular devices, for example, peripheral and intracranial stents, are limited by thrombosis and restenosis. To ameliorate these complications, we developed a technology to promote vessel healing by rapidly seeding (QuickSeeding) autologous blood-derived endothelial cells (ECs) onto modified self-expanding nitinol stent delivery systems immediately before implantation. Several thousand micropores were laser-drilled into a delivery system sheath surrounding a commercial nitinol stent to allow for exit of an infused cell suspension. As suspension medium flowed outward through the micropores, ECs flowed through the delivery system attaching to the stent surface. The QuickSeeded ECs adhered to and spread on the stent surface following 24-h in vitro culture under static or flow conditions. Further, QuickSeeded ECs on stents that were deployed into porcine carotid arteries spread to endothelialize stent struts within 48 h (n = 4). The QuickSeeded stent struts produced significantly more nitric oxide in ex vivo flow circuits after 24 h, as compared to static conditions (n = 5). In conclusion, ECs QuickSeeded onto commercial nitinol stents within minutes of implantation spread to form a functional layer in vitro and in vivo, providing proof of concept that the novel QuickSeeding method with modified delivery systems can be used to seed functional autologous endothelium at the point of care. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1658-1665, 2016.

Effects of tibial plateau angle and spacer thickness applied during in vitro canine total knee replacement on three-dimensional kinematics and collateral ligament strain.

OBJECTIVE: To quantify the 3-D kinematics and collateral ligament strain of stifle joints in cadaveric canine limbs before and after cranial cruciate ligament transection followed by total knee replacement (TKR) involving various tibial plateau angles and spacer thicknesses. SAMPLE: 6 hemi-pelvises collected from clinically normal nonchondrodystrophic dogs (weight range, 25 to 35 kg). PROCEDURES: Hemi-pelvises were mounted on a modified Oxford knee rig that allowed 6 degrees of freedom of the stifle joint but prevented mechanical movement of the hip and tarsal joints. Kinematics and collateral ligament strain were measured continuously while stifle joints were flexed. Data were again collected after cranial cruciate ligament transection and TKR with combinations of 3 plateau angles (0°, 4°, and 8°) and spacer thicknesses (5, 7, and 9 mm). RESULTS: Presurgical (ie, normal) stifle joint rotations were comparable to those previously documented for live dogs. After TKR, kinematics recorded for the 8°, 5-mm implant most closely resembled those of unaltered stifle joints. Decreasing the plateau angle and increasing spacer thickness altered stifle joint adduction, internal rotation, and medial translation. Medial collateral ligament strain was minimal in unaltered stifle joints and was unaffected by TKR. Lateral collateral ligament strain decreased with steeper plateau angles but returned to a presurgical level at the flattest plateau angle. CONCLUSIONS AND CLINICAL RELEVANCE: Among the constructs tested, greatest normalization of canine stifle joint kinematics in vitro was achieved with the steepest plateau angle paired with the thinnest spacer. Furthermore, results indicated that strain to the collateral ligaments was not negatively affected by TKR.