Citations

Background: There is a spectrum of facial paralysis patient presentations from complete flaccid facial paralysis (CFFP) to facial aberrant reinnervation syndrome (FARS). Objective: To objectively compare how laypersons direct attention to faces with different facial paralysis subtypes using eye-tracking technology. Methods: Lay observers freely gazed at standardized videos of 24 individuals’ faces as follows: 8 with CFFP, 8 with FARS, and 8 nonparalyzed Controls performing common facial expressions. Eye-tracking measured observers’ gaze and extracted data as time in milliseconds looking at facial subsites. Mixed effects regression was used for comparative analyses. Results: A total of 85 observers completed the study. For faces at rest, measurable differences in gaze patterns were noted for CFFP faces (more attention spent on nonparalyzed hemiface), whereas FARS and Control faces showed similar symmetric gaze patterns. With dynamic movement (smiling and brow-elevation), gaze patterns for both CFFP and FARS faces became altered and asymmetrical compared with Control faces. Conclusions: Faces with CFFP and FARS are viewed differently by casual observers, which has implications for patient care and future research. While CFFP showed gaze alterations (compared with Control) in both rest and facial expression states, FARS caused gaze alterations only with facial movement.

AbstractBackgroundTandem mass spectrometry (MS/MS) has become a common clinical laboratory testing modality has demonstrated success in distinguishing between small protein variations in transthyretin amyloidosis. Since many common clinically significant RBC antigens are also small protein variations, this study aimed to determine if MS/MS could correctly detect common RBC antigens within the Rh, Kell, Duffy, MNS, Kidd, Diego, and Lutheran blood group systems.Study Design and MethodsResidual samples from serotyped/genotyped blood donors at a hospital‐based blood donation center from February to August 2021 were analyzed. RBC membrane protein preparations underwent protease digestion prior to MS/MS analysis for RhD, RhCE, Kell, atypical chemokine receptor 1 (Duffy), glycophorin A (MNS), glycophorin B (MNS), urea transporter 1 (Kidd), band 3 anion transport protein (Diego), and basal cell adhesion molecule (Lutheran). Untargeted liquid chromatography (LC)‐MS/MS detected protein‐specific peptides, while targeted LC‐selected reaction monitoring (LC‐SRM) detected RBC antigen‐containing peptides.ResultsThrough the use of multiple proteases, untargeted LC–MS/MS detected protein‐specific peptides in all but glycophorin B, with band 3 anion transport protein, basal cell adhesion molecule, Kell, and glycophorin A having the greatest protein sequence coverage. Targeted LC‐SRM detected antigen‐specific peptides for Cw, Dia/Dib, Kpb, and Wra/Wrb, which agreed with the donors' previous typing results.DiscussionMS/MS can successfully detect peptides from several blood group systems but only detected a subset of their common RBC antigens. Further sample enrichment and MS/MS detection improvements will need to occur before MS/MS could be considered a clinical RBC phenotyping modality.

ABSTRACT Background As Coccidioides spp. are endemic in the southwestern United States, awareness of the risk factors for severe disease and dissemination is important to avoid delays in diagnosis and treatment. In addition to immunocompetent patients, individuals of certain ethnic backgrounds, especially African and Filipino ancestry, are at higher risk for dissemination. Diagnostic testing may be complicated by the lack of available invasive specimens for histopathologic examination and culture. Case Summary A 29-year-old African American woman presented with a 6-year history of abdominal bloating and discomfort, which was previously diagnosed as endometriosis and possible irritable bowel syndrome. After multiple visits to primary care, urgent care, and emergency settings, she was referred for outpatient gynecology and gastrointestinal follow-up. Imaging revealed diffuse peritoneal nodules potentially concerning for malignancy, and biopsies revealed Coccidioides spp. spherules on the frozen section. Routine bacterial and fungal cultures from the biopsied nodules grew Coccidioides immitis/posadasii . The patient was placed on fluconazole with rapid symptom resolution and was maintained on fluconazole at a 2-year follow-up. Conclusion The case presented highlights a reasonably common occurrence in endemic regions—the delayed diagnosis of coccidioidomycosis due to the lack of consideration as the etiology of the patient’s symptoms. This patient was at risk for dissemination due to her ethnicity, and while the differential for her presenting symptoms was broad, coccidioidomycosis should have been considered. In immunocompetent patients, like the case presented, serologic testing should be pursued, as severe or disseminated cases typically have positive IgG responses.

ABSTRACTThe optimal conditioning schedule and CD34+ cell dose for autologous stem cell transplantation (ASCT) for AL amyloidosis is unknown. Patients (n = 1704) who underwent ASCT for AL amyloidosis between 2003 and 2020 in 9 centers were included. Data on melphalan conditioning dose, number of conditioning days, whether a rest day between conditioning and stem cell infusion was given or not, and infused CD34+ cell dose were collected. Full‐dose melphalan (≥ 180 mg/m2) was administered in 63.7% of the patients, and 80.4% had melphalan split into 2‐day conditioning. A rest day (day −1) between the conditioning regimen and stem cell infusion was provided in 52.5% of patients. The median infused CD34+ cell count was 4.7 × 106/kg. An infused CD34+ cell count ≥ 4.5 × 106/kg was associated with a shorter time to neutrophil and platelet engraftment. In a nominal regression analysis, full‐dose melphalan, 1‐day melphalan conditioning, and omitting a rest day between conditioning and stem cell infusion were independent predictors of post‐ASCT higher deep hematological response. The median follow‐up was 8.6 years, and 38% of patients died. Independent predictors of superior overall survival in multivariate Cox regression analysis included full‐dose melphalan, having no rest day, and infused CD34+ cells ≥ 4.5 × 106/kg. Independent predictors of higher day‐100 transplant‐related mortality (TRM) in nominal logistic regression analysis included poorer performance status, NT‐proBNP/BNP ≥ 1800/400 pg/mL, serum albumin < 2.5 g/dL, CD34+ cells < 4.5 × 106/kg, and not having a rest day. In conclusion, 1 day of melphalan conditioning and administration of CD34+ cells ≥ 4.5 × 106/kg are recommended for ASCT in AL amyloidosis.

Abstract Oligodendrogliomas are initially slow-growing brain tumors that are prone to malignant transformation despite surgery and cytotoxic therapy. Understanding of oligodendroglioma evolution and new treatments for patients have been encumbered by a paucity of patient-matched newly diagnosed and recurrent tumor samples for multiplatform analyses, and by a lack of preclinical models for interrogation of therapeutic vulnerabilities that drive oligodendroglioma growth. Here we integrate spatial and functional analyses of tumor samples and patient-derived organoid co-cultures to show that synaptic connectivity is a hallmark of oligodendroglioma evolution and recurrence. We find that patient-matched recurrent oligodendrogliomas are enriched in synaptic gene expression programs irrespective of previous therapy or histologic grade. Analyses of spatial, single-cell, and clinical data reveal epigenetic misactivation of synaptic genes that are concentrated in regions of cortical infiltration and can be used to predict eventual oligodendroglioma recurrence. To translate these findings to patients, we show that local field potentials from tumor-infiltrated cortex at the time of resection and neuronal hyperexcitability and synchrony in patient-derived organoid co-cultures are associated with oligodendroglioma proliferation and recurrence. In preclinical models, we find that neurophysiologic drugs block oligodendroglioma growth and pathologic electrophysiology. These results elucidate mechanisms underlying oligodendroglioma evolution from an indolent tumor to a fatal disease and shed light on new biomarkers and new treatments for patients.

Background: Facial aberrant reinnervation syndrome (FARS) is a common sequelae of facial nerve injury followed by aberrant reinnervation and recovery. Patients with FARS can present with different patterns of facial synkinesis, facial muscle hypertonicity, and facial spasm/twitching. 1 Synkinesis associated with FARS is described as undesired muscle contraction when a voluntary movement is triggered. One of the most common and bothersome types of facial synkinesis is oral-ocular synkinesis, where patients experience unwanted eyelid closure with movement of the mouth such as smiling or pursing the lips. First-line treatment options for FARS include facial physical therapy and botulinum toxin selective chemodenervation. For patients with persistent or more significant symptoms, there are surgical options, including selective neurectomy and selective myectomy of the involved facial nerve branches and muscles. 2 , 3 Selective myectomy of the orbicularis oculi muscle has been shown to be an effective surgical treatment option for oral-ocular synkinesis. 3 – 4 There is nuance to this procedure, including deciding whether to target the upper eyelid, lower eyelid, or both, as well as which segments and how much of the orbicularis oculi muscle to remove, balancing the goals of improving synkinesis and hypertonicity while avoiding the creation of lagophthalmos. The novel implementation of autologous microfat grafting to the procedure can help improve postoperative eyelid volume and contour and may help prevent the cut edges of the muscle from fusing, thus reducing the likelihood of persistent or recurrent ocular synkinesis. Objective: To describe a selective myectomy of the orbicularis oculi with the novel addition of autologous microfat grafting for the treatment of oral-ocular synkinesis. Methods: This video demonstrates the procedural steps for a selective myectomy of the orbicularis oculi with autologous microfat grafting for a patient with oral-ocular synkinesis due to FARS. In addition, it demonstrates the preparation of harvested abdominal fat that is utilized for the autologous microfat grafting. Results: Selective myectomy of the orbicularis oculi with autologous microfat grafting has been routinely performed safely and effectively by the senior author for treatment of oral-ocular synkinesis. Postoperative aesthetic eyelid shape and functional results have been reassuring with improvements up to 1 year postoperative and a need for additional long-term follow-up. Conclusion: To the authors’ knowledge, a selective myectomy of the orbicularis oculi with autologous microfat grafting has not been demonstrated in video documentation. Autologous microfat grafting may be a helpful addition to selective myectomy of the orbicularis oculi to enhance both eyelid aesthetics and function. Patient Consent Statement: All patients included in the video have consented to the use of videos and photographs of their faces for research and educational purposes. Funding and Conflicts of Interest: The authors have no funding, financial relationships, or conflicts of interest to disclose. Runtime of video: 7 mins 11 secs.

Background: Benefits of hospice care, such as improvement in quality of life and reduced costs, depend on duration of enrollment in hospice services, making timely hospice referral essential. Patient-, provider-, and system-level factors associated with hospice referral timing and length of stay (LOS) are unclear. 1 – 6 Objective: To review existing hospice referral patterns to identify patient- and system-level factors associated with hospice LOS. Methods: We performed a retrospective review of all adult patients referred from our institution (located in Rochester, Minnesota, USA) to a nonprofit hospice agency between 2013 and 2017. The primary dependent variable was hospice LOS. Patient-level variables included demographic characteristics, place of residence, and hospice diagnosis. System-level variables included referral setting and provider-specific variables, such as title and gender. Statistical analyses were performed using multivariate logistic regression. Results: A total of 2072 patients were referred to hospice during the study period. Patient-level factors associated with LOS included hospice diagnosis and place of residence. Patients referred for cancer had a higher odds of a long LOS, while patients from long-term care facilities had a higher odds of a short LOS. System-level factors associated with LOS included provider gender and title. Referral by a female provider or by a physician, rather than an advanced practice provider, was associated with a lower odds of a short LOS. Conclusion: Based on a review of hospice referral patterns, the integration of hospice care into subspecialty practices, long-term care facilities, and advanced practice education could be an effective strategy to improve hospice LOS.

Abstract The incidence of hypertensive disorders of pregnancy is increasing, which may be due to several factors, including an increased age at pregnancy and more comorbid health conditions during reproductive years. Preeclampsia, the most severe hypertensive disorder of pregnancy, has been associated with an increased risk of future disease, including cardiovascular and kidney diseases. Cellular senescence, the process of cell cycle arrest in response to many physiologic and maladaptive stimuli, may play an important role in the pathogenesis of preeclampsia and provide a mechanistic link to future disease. In this article, we will discuss the pathophysiology of preeclampsia, the many mechanisms of cellular senescence, evidence for the involvement of senescence in the development of preeclampsia, as well as evidence that cellular senescence may link preeclampsia to the risk of future disease. Lastly, we will explore how a better understanding of the role of cellular senescence in preeclampsia may lead to therapeutic trials. © 2023 American Physiological Society. Compr Physiol 13:5077‐5114, 2023.