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Importance In-person interviews have traditionally been considered a crucial component of the residency application process. Virtual interviews (VIs) became the standard format for the 2020 to 2021 application cycle due to the novel coronavirus disease 2019 (COVID-19) pandemic. VIs offer a new perspective and challenge to this process which warrants unique considerations and further understanding of effects on applicants. Objective This study aimed to assess the perceived efficacy of a VI preparedness exercise for ophthalmology residency applicants in the 2021 residency application cycle. Design, Setting, and Participants A cross-sectional survey was distributed online. All participants in a mock VI exercise conducted via video-telecommunication technology were invited to complete the survey. Data collection occurred from October 12, 2020, to November 2, 2020. A follow-up survey after a match results released was distributed to all participants and data collection occurred from February 18, 2021, to February 25, 2021. Main Outcome and Measures Applicant demographics, comfort, and attitudes toward VIs and VI practice were the primary measurements of this study. Results Responses to the initial survey were received from all 35 participants (100%) in the VI mock interviews. There was a statistically significant difference between the pre- and postinterview responses for “How prepared do you feel for virtual interviews with residency programs?” (p = 0.0003) and “How likely are you to practice virtual interviews with someone you know?” (p = 0.0023). Participants reported feeling more prepared for VIs with residency programs after the mock interview (p = 0.002). A greater proportion of participants responded with “Very Likely” after the mock interview in comparison to before the interview to the questions “How likely are you to practice interviews with someone you know?” (p = 0.039) and “How likely are you to practice virtual interviews in the same room/area as you will during the official interview season?” (p = 0.021). Of the 35 original participants, 20 completed the follow-up survey. There were an equal number of participants who responded either “Helped Somewhat” (n = 9) or “Helped Greatly” (n = 9) to “How much did the VI mock exercise help you for the actual interview season?” in the follow-up survey. The majority of follow-up survey respondents (17/20) reported that they had additional practice in the virtual environment for interviews after the VI mock exercise. There was no significant difference in perceived helpfulness of the VI mock exercise during the actual interview season between matched and unmatched participants. Conclusion and Relevance As residency applicants prepare for future VIs, practice and adequate preparation will be essential. In this study, implementation of a VI preparedness exercise had a positive impact on applicants' perception of their preparedness and intention to practice the format in the future.

ObjectiveHereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism.MethodsWe describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes.ResultsFibroblasts prepared from patients with SPG15 have selective enlargement of LAMP1-positive structures, and they consistently exhibited abnormal lysosomal storage by electron microscopy. A similar enlargement of LAMP1-positive structures was also observed in cells from multiple SPG11 patients, though prominent abnormal lysosomal storage was not evident. The stabilities of the SPG15 protein spastizin/ZFYVE26 and the SPG11 protein spatacsin were interdependent.InterpretationEmerging studies implicating these two proteins in interactions with the late endosomal/lysosomal adaptor protein complex AP-5 are consistent with shared abnormalities in lysosomes, supporting a converging mechanism for these two disorders. Recent work with Zfyve26-/- mice revealed a similar phenotype to human SPG15, and cells in these mice had endolysosomal abnormalities. SPG15 and SPG11 are particularly notable among HSPs because they can also present with juvenile parkinsonism, and this lysosomal trafficking or storage defect may be relevant for other forms of parkinsonism associated with lysosomal dysfunction.

Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a clinically heterogeneous maculopathy that may mimic other conditions and be difficult to diagnose. It is characterized by late onset, slow progression and high variability in morphologic and functional alterations. Diagnostic evaluation should include careful ophthalmoscopy and imaging studies. The typical ophthalmoscopic findings are bilateral, asymmetric, foveal or perifoveal, yellow, solitary, round to oval elevated subretinal lesions, often with central pigmentation. The lesions characteristically demonstrate increased autofluorescence and hypofluorescent lesions surrounded by irregular annular hyperfluorescence on fluorescein angiography. Optical coherence tomography studies demonstrate homogenous or heterogeneous hyperreflective material between the retinal pigment epithelium and the neurosensory retina. The visual prognosis is generally favorable, but visual loss can occur from chorioretinal atrophy and choroidal neovascularization.

Ameloblastic fibro-odontoma (AFO) is a rare benign mixed odontogenic tumor composed of proliferating odontogenic epithelium in a cellular ectomesenchyme with the formation of dental hard tissues, including enamel and dentin. According to the 2017 WHO Classification of Head and Neck Tumours, AFO is no longer defined as an independent entity but as part of a series of histological changes observed in a developing odontoma (DOD). Nevertheless, it is believed that this classification does not apply to all lesions diagnosed as AFO before 2017, some of which have neoplastic characteristics with BRAF p.V600E mutation. We report a case of DOD in the posterior mandible of an 8-year-old girl. Surgical excision was performed under general anesthesia. This case was diagnosed based on detailed clinical, radiological, and histopathological analyses. In addition, the mutant BRAF p.V600E was suspected by immunohistochemical analysis. BRAF mutation detection may contribute to accurately diagnosing the true neoplastic nature in odontomas. In the present case, no recurrence was observed until at least 11 months after surgery. [ABSTRACT FROM AUTHOR]

Background and Objective: The objective was to evaluate factors associated with clinical presentation of uveal melanoma (UM) during the initial two years of the coronavirus disease 2019 pandemic. Patients and Methods: This was a multi-site, retrospective cohort study of patients treated for uveal melanoma during the first (early) and second (late) year of the pandemic compared with the year prior (control). Results: A total of 48, 67, and 75 patients were in the control, early, and late cohorts, respectively. The early cohort had a higher frequency of large tumors (control: 29.2%, early: 40.3%, late: 29.3%; P < 0.001) at presentation. Both the early and late cohorts had higher rates of enucleation (control: 8.33%, early: 20.9%, late: 18.67%; P ≤ 0.0338) compared to the control cohort. Conclusions: While there was an increase in large tumors along with a rise in enucleation during the first year of the pandemic, enucleation rates remained elevated even while tumor sizes normalized. [Ophthalmic Surg Lasers Imaging Retina 2024;55:278–284.] [ABSTRACT FROM AUTHOR]

Objectives To evaluate the long-term impact of immunosuppressive therapeutic agents on antibody response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with autoimmune rheumatic diseases (AIRD) in order to propose a strategy for annual vaccination. Methods This prospective multicentre cohort study evaluated the humoral response to second and third BNT162b2 and/or mRNA-1273 vaccines in 382 Japanese AIRD patients classified into 12 different medication groups and in 326 healthy controls (HCs). The third vaccination was administered six months after the second vaccination. Antibody titres were measured using the Elecsys Anti-SARS-CoV-2 S assay. Results The seroconversion rate and antibody titres were lower in AIRD patients than in HCs 3–6 weeks after the second vaccination and 3–6 weeks after the third vaccination. Seroconversion rates were <90% after the third vaccination in patients receiving mycophenolate mofetil and rituximab. Antibody levels after the third vaccination were significantly lower in the groups prescribed TNF inhibitor with or without methotrexate, abatacept and rituximab or cyclophosphamide than those of HCs in a multivariate analysis adjusting for age, sex, and glucocorticoid dosage. The third vaccination induced an adequate humoral response in patients treated with sulfasalazine, bucillamine, methotrexate monotherapy, iguratimod, interleukin-6 inhibitors or calcineurin inhibitors including tacrolimus. Conclusions Repeated vaccinations in many immunosuppressed patients produced antibody responses similar to those observed in HCs. In contrast, annual vaccination in patients receiving TNF inhibitors, abatacept, mycophenolate mofetil and rituximab may require caution. [ABSTRACT FROM AUTHOR]

Abstract Background Intra-articular tranexamic acid (TXA) as an adjunct to intravenous TXA was reported to decrease perioperative blood loss during unilateral total knee arthroplasty (TKA). However, there have been no randomized controlled trials comparing intravenous versus combined intravenous and intra-articular TXA administration in patients undergoing simultaneous bilateral TKA. Methods We randomly assigned 77 patients with 154 involved knees undergoing simultaneous bilateral TKA to the intravenous TXA group (intra-articular placebo for each knee) or combined TXA group (1000 mg of intra-articular TXA for each knee) with 1:1 treatment allocation. In both groups, 1000 mg of TXA was given intravenously twice, just before surgery and 6 h after the initial administration. Other perioperative medications, surgical procedures, and blood management strategies were the same for all patients. The primary outcome was perioperative blood loss calculated from blood volume and change in hemoglobin from preoperative to postoperative day 3. Results Intention-to-treat analysis showed no statistically significant differences in perioperative blood loss until postoperative day 3 (1067 ± 403 mL in the intravenous TXA group vs. 997 ± 345 mL in the combined TXA group [95% CI, − 240 to 100 mL], P = 0.42). No patients required allogenic blood transfusion. The incidence of thrombotic events did not differ between groups (12% in the intravenous TXA group vs. 9% in the combined TXA group; P = 0.73). Conclusions The addition of intra-articular TXA did not reduce perioperative blood loss in patients undergoing simultaneous bilateral TKA compared with placebo. Trial registration University Hospital Medical Information Network UMIN000026137. Registered 14 February 2017.

We report the case of a 48-year-old man with thyroid storm associated with fulminant hepatitis and elevated levels of soluble interleukin-2 receptor (sIL-2R). Fatigue, low-grade fever, shortness of breath, and weight loss developed over several months. The patient was admitted to the hospital because of tachycardia-induced heart failure and liver dysfunction. Graves’ disease with heart failure was diagnosed. He was treated with methimazole, inorganic iodide, and a β-blocker. On the day after admission, he became unconscious with a high fever and was transferred to the intensive care unit. Cardiogenic shock with atrial flutter was treated with intra-aortic balloon pumping and cardioversion. Hyperthyroidism decreased over 10 days, but hepatic failure developed. He was diagnosed with thyroid storm accompanied by fulminant hepatitis. Laboratory investigations revealed elevated levels of sIL-2R (9770 U/mL). The fulminant hepatitis was refractory to plasma exchange and plasma filtration with dialysis, and no donors for liver transplantation were available. He died of hemoperitoneum and gastrointestinal hemorrhage due to fulminant hepatitis 62 days after admission. Elevated circulating levels of sIL-2R might be a marker of poor prognosis in thyroid storm with fulminant hepatitis.

Abstract Background α-Dystroglycan is the highly glycosylated component of the dystrophin-glycoprotein complex (DGC) that binds with high-affinity to extracellular matrix (ECM) proteins containing laminin-G-like (LG) domains via a unique heteropolysaccharide [-GlcA-beta1,3-Xyl-alpha1,3-]n called matriglycan. Changes in expression of components of the DGC or in the O-glycosylation of α-dystroglycan result in muscular dystrophy but are also observed in certain cancers. In mice, the loss of either of two DGC proteins, dystrophin or α-sarcoglycan, is associated with a high incidence of rhabdomyosarcoma (RMS). In addition, glycosylation of α-dystroglycan is aberrant in a small cohort of human patients with RMS. Since both the glycosylation of α-dystroglycan and its function as an ECM receptor require over 18 post-translational processing enzymes, we hypothesized that understanding its role in the pathogenesis of RMS requires a complete analysis of the expression of dystroglycan-modifying enzymes and the characterization of α-dystroglycan glycosylation in the context of RMS. Methods A series of cell lines and biopsy samples from human and mouse RMS were analyzed for the glycosylation status of α-dystroglycan and for expression of the genes encoding the responsible enzymes, in particular those required for the addition of matriglycan. Furthermore, the glycosyltransferase LARGE1 was ectopically expressed in RMS cells to determine its effects on matriglycan modifications and the ability of α-dystroglycan to function as a laminin receptor. Results Immunohistochemistry and immunoblotting of a collection of primary RMS tumors show that although α-dystroglycan is consistently expressed and glycosylated in these tumors, α-dystroglycan lacks matriglycan and the ability to bind laminin. Similarly, in a series of cell lines derived from human and mouse RMS, α-dystroglycan lacks matriglycan modification and the ability to bind laminin. RNAseq data from RMS cell lines was analyzed for expression of the genes known to be involved in α-dystroglycan glycosylation, which revealed that, for most cell lines, the lack of matriglycan can be attributed to the downregulation of the dystroglycan-modifying enzyme LARGE1. Ectopic expression of LARGE1 in these cell cultures restored matriglycan to levels comparable to those in muscle and restored high-affinity laminin binding to α-dystroglycan. Conclusions Collectively, our findings demonstrate that a lack of matriglycan on α-dystroglycan is a common feature in RMS due to the downregulation of LARGE1, and that ectopic expression of LARGE1 can restore matriglycan modifications and the ability of α-dystroglycan to function as an ECM receptor.

A 75-year-old pedestrian was struck by a truck and in shock with both lower extremities significantly deformed, with injuries extending proximally to the inguinal region and degloving injuries. Resuscitative endovascular balloon occlusion of the aorta was performed to achieve temporary hemostasis and the patient became hemodynamically stable. Following stabilization, both lower extremities were amputated. Resuscitative endovascular balloon occlusion of the aorta may be effective to achieve temporary hemostasis in patients with extensive injuries of the lower extremities, especially with extension to the inguinal region which precludes use of a tourniquet. Keywords: Bilateral lower extremity injuries, Hemorrhagic shock, Resuscitative endovascular balloon occlusion of the aorta (REBOA), Temporary hemostasis

We report a case of rapid pleural effusion after discontinuation of lenvatinib. A 73-year-old woman was diagnosed with poorly differentiated thyroid cancer with right pleural metastasis. Weekly paclitaxel treatment was performed for 18 weeks, but it was not effective. Oral administration of lenvatinib, a multi-target tyrosine kinase inhibitor, reduced the size of cervical and thoracic tumors and lowered serum thyroglobulin levels. Lenvatinib was discontinued on day 28 because of Grade 2 thrombocytopenia and Grade 3 petechiae. Seven days after discontinuation of lenvatinib, the patient was hospitalized because of dyspnea and right pleural effusion. Pleural effusion rapidly improved with drainage and re-initiation of lenvatinib and did not recur. Anorexia caused by lenvatinib led to undernutrition, which resulted in death 13 months after initiation of lenvatinib. Autopsy revealed extensive necrosis with primary and metastatic lesions, suggesting that the patient responded to lenvatinib. Physicians should be aware of the possibility of flare-up in patients with thyroid cancer treated with lenvatinib.

The appropriate differentiation of endometrial stromal cells (ESCs) into decidual cells is required for embryo implantation and subsequent placentation into humans. Decidualization is accompanied by the appearance of senescent-like cells. We recently reported the secretory phase-specific downregulation of endometrial progesterone receptor membrane component 1 (PGRMC1) and enhanced decidualization upon PGRMC1 knockdown and inhibition in cultured ESCs. However, it remains unknown whether PGRMC1 is involved in cellular senescence during decidualization. Here, we showed that the small interfering RNA (siRNA)-mediated knockdown of PGRMC1 and the inhibition of PGRMC1 by AG-205 increased the expression of the transcription factor forkhead box protein O1 (FOXO1) and the senescence-associated β-galactosidase activity in cAMP analog- and progesterone-treated ESCs. Furthermore, the knockdown of FOXO1 repressed the decidual senescence induced by siRNA-based PGRMC1 knockdown or AG-205 treatment. Taken together, the decreased PGRMC1 expression in ESCs may accelerate decidualization and cellular senescence via the upregulation of FOXO1 expression for appropriate endometrial remodeling and embryo implantation during the secretory phase.