Mayo Foundation Research Articles

Linking adipose tissue eosinophils, IL-4, and leptin in human obesity and insulin resistance.

BACKGROUNDObesity is a multifactorial disease with adverse health implications including insulin resistance (IR). In patients with obesity, the presence of high circulating levels of leptin, deemed hyperleptinemia, is associated with IR. Recent data in mice with diet-induced obesity (DIO) show that a partial reduction in leptin levels improves IR. Additional animal studies demonstrate that IL-4 decreases leptin levels. In rodents, resident adipose tissue eosinophils (AT-EOS) are the main source of IL-4 and are instrumental in maintaining metabolic homeostasis. A marked reduction in AT-EOS content is observed in animal models of DIO. These observations have not been explored in humans.METHODSWe analyzed AT from individuals with obesity and age-matched lean counterparts for AT-EOS content, IL-4, circulating leptin levels, and measures of IR.RESULTSOur results show that individuals with obesity (n = 15) had a significant reduction in AT-EOS content (P < 0.01), decreased AT-IL-4 gene expression (P = 0.02), and decreased IL-4 plasma levels (P < 0.05) in addition to expected IR (P < 0.001) and hyperleptinemia (P < 0.01) compared with lean subjects (n = 15). AT-EOS content inversely correlated with BMI (P = 0.002) and IR (P = 0.005). Ex vivo AT explants and in vitro cell culture of primary human mature adipocytes exposed to either IL-4 or EOS conditioned media produced less leptin (P < 0.05).CONCLUSIONOur results suggest that IL-4 acts as a link between EOS, AT, and leptin production. Future studies exploring this interaction may identify an avenue for the treatment of obesity and its complications through amelioration of hyperleptinemia.TRIAL REGISTRATIONClinicaltrials.gov NCT02378077 & NCT04234295.

Leonard Rowntree, Louis Wilson, Fielding Garrison, and the origins of teaching medical history at the Mayo Clinic

A visiting surgeon described his disappointment with an aspect of the Mayo Clinic in 1914, stating that there was “the almost lack of anything that could be dignified by the term ‘lecture.’” One year later, the Mayo Foundation for Medical Education and Research was founded. By 1917, the foundation declared history of medicine a graduate-level subject, and history of medicine questions were included in final oral examinations. In 1920 and 1921, lectures were given on historical topics; however, these lectures petered out, and there were no historical lectures in the official curriculum of 1923 or 1924. Enter Leonard Rowntree, who in 1926 proposed a lecture series on the history of medicine. Rowntree wrote to Fielding Garrison in early 1927 to ask for assistance selecting speakers. The two men corresponded and developed a list of eminent medical historians to invite, including Sir Charles Ballance, William Welch, and Garrison himself. These lectures served to enrich the greater Midwestern medical community as well thanks to Louis Wilson. Then head of the Mayo Foundation, Wilson wrote to nearby institutions to create a lecture circuit for speakers who traveled to the Mayo Clinic. Ultimately, the lectures were published as a book in 1933.

Association between hearing loss and development of dementia using formal behavioural audiometric testing within the Mayo Clinic Study of Aging (MCSA): a prospective population-based study

Hearing loss has been identified as a potential major modifiable risk factor for developing dementia. This study examined associations between formal behavioural pure-tone and speech audiometry assessed by an audiologist with development of dementia in the Mayo Clinic Study of Aging (MCSA). The MCSA is a prospective population-based study examining the incidence, prevalence, and risk factors of mild cognitive impairment and dementia in Olmsted County, Minnesota, USA. Participants undergo clinical examinations with neuropsychological testing at enrolment and every 15 months. Participants were 50 years or older at enrolment between Nov 29, 2004, and Dec 23, 2019, who underwent formal behavioural audiometric evaluation by an audiologist due to concerns about hearing loss or as a part of annual comprehensive health assessments. Associations of pure-tone average (PTA) and word recognition scores (WRS) with the development of dementia were evaluated using Cox proportional hazards regression with age as the timescale, and associations with changes in cognitive testing scores over time were evaluated using linear mixed-effects models. Among 1200 eligible participants, the mean age at enrolment was 79 years (SD 9), 593 (49%) were men, and 207 developed dementia during a mean of 7·0 years (SD 3·7) of follow-up. After adjusting for sex, years of education, smoking status, diabetes, hypertension, apolipoprotein E ε4 carriership, and hearing rehabilitation (defined as hearing aid or cochlear implant use), neither PTA (hazard ratio [HR] per 10-decibels hearing level increase of 0·99 (95% CI 0·89-1·12; p=0·91) nor WRS (HR per 10% decrease of 0·98, 95% CI 0·89-1 ·07; p=0·65) was significantly associated with the development of dementia. However, both PTA and WRS were significantly associated with poorer performance in cognitive testing over time: participants with a PTA higher than 25 decibels hearing level or a WRS lower than 100% had significantly worse declines in cognitive testing scores. Informant-based hearing difficulties assessed by the participant's study partner were significantly associated with the development of dementia (HR 1·95, 95% CI 1·45-2·62; p<0·0001). In this prospective population-based study, subjective informant-based hearing difficulties were associated with development of dementia, whereas objective measures on formal behavioural audiometry were predictive of poorer performance on cognitive testing over time but not the development of dementia. Other factors related to central processing might potentiate the effects of peripheral hearing loss detected on behavioural audiometric testing. National Institute of Health, the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic, the GHR Foundation, the Mayo Foundation for Medical Education and Research, the Liston Award, the Schuler Foundation, the Rochester Epidemiology Project medical records linkage system, and the National Institute on Aging.

Multimorbidity and Mortality Models to Predict Complications Following Percutaneous Coronary Interventions.

Previous percutaneous coronary intervention risk models were focused on single outcome, such as mortality or bleeding, etc, limiting their applicability. Our objective was to develop contemporary percutaneous coronary intervention risk models that not only determine in-hospital mortality but also predict postprocedure bleeding, acute kidney injury, and stroke from a common set of variables. We built risk models using logistic regression from first percutaneous coronary intervention for any indication per patient (n=19 322, 70.6% with acute coronary syndrome) using the Mayo Clinic registry from January 1, 2000 to December 31, 2016. Approval for the current study was obtained from the Mayo Foundation Institutional Review Board. Patients with missing outcomes (n=4183) and those under 18 (n=10) were removed resulting in a sample of 15 129. We built both models that included procedural and angiographic variables (Models A) and precatheterization model (Models B). Death, bleeding, acute kidney injury, and stroke occurred in 247 (1.6%), 650 (4.3%), 1184 (7.8%), and 67 (0.4%), respectively. The C statistics from the test dataset for models A were 0.92, 0.70, 0.77, and 0.71 and for models B were 0.90, 0.67, 0.76, and 0.71 for in-hospital death, bleeding, acute kidney injury, and stroke, respectively. Bootstrap analysis indicated that the models were not overfit to the available dataset. The probabilities estimated from the models matched the observed data well, as indicated by the calibration curves. The models were robust across many subgroups, including women, elderly, acute coronary syndrome, cardiogenic shock, and diabetes. The new risk scoring models based on precatheterization variables and models including procedural and angiographic variables accurately predict in-hospital mortality, bleeding, acute kidney injury, and stroke. The ease of its application will provide useful prognostic and therapeutic information to both patients and physicians.

Rag GTPase critically contributes to humoral immunity independent of canonical mTORC1 signaling

Abstract The humoral immune response requires that B cells undergo a rapid metabolic shift and high demand of nutrients, which are vital to sustain the formation of germinal center. Rag GTPase senses amino acid availability to activate mechanistic target of rapamycin complex 1(mTORC1) pathway and modulate the function of transcription factor EB (TFEB), a member of the microphthalmia (MiT/TFE) family of HLH-leucine zipper transcription factors. However, little is known about how Rag GTPase coordinates amino acid sensing, mTORC1 activation and TFEB activity in humoral immune response. Here, we show that B cell intrinsic Rag GTPase is critical to the development and activation of B cells. Disruption of Rag GTPase complex, but not mTORC1 complex, abrogates germinal center formation, antibody production as well as plasma cell generation upon respiratory influenza infection. Mechanistically, the Rag GTPase complex senses specific amino acids to suppress TFEB activity, independent of canonical mTORC1 activation. Collectively, our data support the idea that Rag GTPase critically contributes to humoral immunity partly through suppressing TFEB and it is largely not necessary for canonical mTORC1 signaling. Supported by Mayo Foundation for Medical Education and Research

MTORC2 contributes to murine lupus associated immunopathology

Abstract The development of systemic lupus erythematosus (SLE) is associated with overactivation of the type I interferon (IFN) pathway, lymphopenia, and increased follicular helper T (Tfh) cell differentiation. However, the cellular and molecular mechanisms of action of type I IFN in SLE remains incompletely understood. Here we show that type I IFN activates the mechanistic target of rapamycin complex 2 (mTORC2) in T cells to promote T cell lymphopenia. mTORC2 also promotes Tfh differentiation and disrupts Treg homeostasis. Inactivation of mTORC2 greatly ameliorated the immunopathology in a lupus-prone mouse model, associated with reduced Tfh differentiation, normalization of Treg homeostasis and reduced T cell glucose metabolism. These data indicate that mTORC2 acts downstream of type I IFN and costimulatory receptor ICOS, to promote T cell lymphopenia and Tfh differentiation in murine lupus development, suggesting that inhibition of mTORC2 could limit lupus disease progression. Supported by Lupus Research Alliance Mayo Foundation for Medical Education and Research R01AR077518

Issue Information

Journal of Clinical NursingVolume 31, Issue 3-4 p. i-i COVER IMAGEFree Access Issue Information First published: 23 January 2022 https://doi.org/10.1111/jocn.16222AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Graphical Abstract The cover image is based on the Special Issue Discursive Paper A practice-based model to guide nursing science and improve the health and well-being of patients and caregivers by Sherry S. Chesak et al., https://doi.org/10.1111/jocn.15837. Used with permission of Mayo Foundation for Medical Education and Research, all rights reserved. Volume31, Issue3-4February 2022Pages i-i RelatedInformation

Circulating autoreactive proteinase 3+ B cells and tolerance checkpoints in ANCA-associated vasculitis.

BACKGROUNDLittle is known about the autoreactive B cells in antineutrophil cytoplasmic antibody–associated (ANCA-associated) vasculitis (AAV). We aimed to investigate tolerance checkpoints of circulating antigen-specific proteinase 3–reactive (PR3+) B cells.METHODSMulticolor flow cytometry in combination with bioinformatics and functional in vitro studies were performed on baseline samples of PBMCs from 154 well-characterized participants of the RAVE trial (NCT00104299) with severely active PR3-AAV and myeloperoxidase-AAV (MPO-AAV) and 27 healthy controls (HCs). Clinical data and outcomes from the trial were correlated with PR3+ B cells (total and subsets).RESULTSThe frequency of PR3+ B cells among circulating B cells was higher in participants with PR3-AAV (4.77% median [IQR, 3.98%–6.01%]) than in participants with MPO-AAV (3.16% median [IQR, 2.51%–5.22%]) and participants with AAV compared with HCs (1.67% median [IQR, 1.27%–2.16%], P < 0.001 for all comparisons), implying a defective central tolerance checkpoint in patients with AAV. Only PBMCs from participants with PR3-AAV contained PR3+ B cells capable of secreting PR3-ANCA IgG in vitro, proving they were functionally distinct from those of participants with MPO-AAV and HCs. Unsupervised clustering identified subtle subsets of atypical autoreactive PR3+ memory B cells accumulating through the maturation process in patients with PR3-AAV. PR3+ B cells were enriched in the memory B cell compartment of participants with PR3-AAV and were associated with higher serum CXCL13 levels, suggesting an increased germinal center activity. PR3+ B cells correlated with systemic inflammation (C-reactive protein and erythrocyte sedimentation rate, P < 0.05) and complete remission (P < 0.001).CONCLUSIONThis study suggests the presence of defective central antigen-independent and peripheral antigen-dependent checkpoints in patients with PR3-AAV, elucidating the selection process of autoreactive B cells.Trial registrationClinicalTrials.gov NCT00104299.FundingThe Vasculitis Foundation, the National Institute of Allergy and Infectious Diseases of the NIH, and the Mayo Foundation for Education and Research.

A 73-year-old woman with delayed intra-abdominal and systemic sepsis following complicated aortobifemoral bypass

A 73-year-old woman with delayed intra-abdominal and systemic sepsis following complicated aortobifemoral bypass

Point of Care Virtual Surgical Planning and Three-Dimensional Printing for Feminizing Foreheadplasty.

Point of Care Virtual Surgical Planning and Three-Dimensional Printing for Feminizing Foreheadplasty.

Microsurgical Resection of Dorsal Pontine Cavernous Malformation: The Telovelar Approach Augmented by the Tonsillouvular Fissure Exposure: 2-Dimensional Operative Video.

Surgical approaches to lesions of the fourth ventricle (FV) have been modified over the years to reduce the complications associated with splitting the inferior cerebellar vermis (ICV) and disrupting the brainstem and critical surrounding structures.1-4 Two common approaches to lesions of this region include the transvermian approach (TVA) and telovelar approach (TeVA).2 The TVA was initially considered the conventional route of access to lesions of the FV1 but has been associated with significant risks, including possible gait ataxia and dysarthria.3 The TeVA is advantageous, as it involves dissection along natural clefts and division of non-neural tissue and provides good exposure of the superolateral recess with modest exposure of the rostral FV. The TeVA approach can be augmented by opening the tonsilouvular fissures (TUFs). This added dissection allows greater lateral and superior exposure with less need for retraction. In this operative video, we demonstrate a case in which we augmented the TeVA with a TUF dissection to access a dorsal pontine cavernous malformation. We performed a midline suboccipital craniotomy with a C1 posterior laminectomy. TUF dissection was followed by division of the tela choroidea (TC), which allowed for more lateral exposure of the FV and excellent visualization of the cavernous malformation without the need to traverse neural tissue. TeVA augmented by TUF dissection provided adequate access to the dorsal pons for complete resection of the cavernous malformation. The patient consented to the procedure as shown in this operative video and gave informed written consent for use of her images in publication. Anatomic images provided by courtesy of © The Rhoton Collection. http://rhoton.ineurodb.org/. Video © Mayo Foundation for Medical Education and Research, 2021. Used with permission.

Ethical Concerns About Reidentification of Individuals from MRI Neuroimages

Ethical Concerns About Reidentification of Individuals from MRI Neuroimages

Optic Canal Decompression: Concepts and Techniques: 2-Dimensional Operative Video

The optic canal (OC) is a bony channel that transmits the optic nerve (ON) and ophthalmic artery (OphA) as they course through the lesser wing of the sphenoid bone to the orbital apex. The OC is involved in a variety of intracranial and extracranial pathologies,1 and opening of the canal may be necessary in order to achieve adequate exposure, better disease control, and vision preservation.2 Depending on the location of the pathology and its relationship with the optic nerve, the OC may be decompressed through an open transcranial approach or an endoscopic endonasal approach.1,3 OC drilling can be tailored based on the location of the pathology and its extension. Anterior clinoid process and optic strut drilling can be added based on these factors as well.4,5 In this video, we demonstrate the steps of OC drilling in both transcranial microscopic and endoscopic endonasal approaches through a combination of animated illustrations and operative videos. We present 4 cases, including 2 transcranial microscopic and 2 endoscopic endonasal approaches,6 demonstrating OC decompression and its technical nuances. Each case was selected to represent the range of pathologies relevant to OC drilling to allow for a complete understanding of the techniques and concepts required for optimal treatment. An informed written consent has been obtained from each of the patients in this publication. Video © Mayo Foundation for Medical Education and Research. All rights reserved. Copyright information: Bendok BR, Abi-Aad KR, Sattur MG, Welz ME, Hoxworth JM, Lal D. Endoscopic resection of a paraclinoid meningioma extending into the optic canal: 2-dimensional operative video. Operative Neurosurgery. 2018 September 1;15(3):356 by permission of Oxford University Press. Cadaveric images provided by courtesy of: The Rhoton Collection. http://rhoton.ineurodb.org/.

Subchondral Bone Changes Following Sacroiliac Joint Arthrodesis – A Morpho-mechanical Assessment of Surgical Treatment of the Painful Joint

Sacroiliac joint arthrodesis is an ultima ratio treatment option for sacroiliac joint dysfunction. Fusion drastically reduces sacroiliac joint movement providing long-lasting pain-relief associated with tension-relief to the innervated sacroiliac joint structures involved in force closure. To display the bone mineralization distribution patterns of the subchondral bone plate in 3 distinct regions (superior, anterior, and inferior) of the sacral and iliac counterparts of the sacroiliac joint pre- and post-sacroiliac joint arthrodesis and compare patterns of sacroiliac joint dysfunction post-sacroiliac joint fusion with sacroiliac joint dysfunction pre- arthrodesis patterns and those from healthy controls. An observational study. The research took place at the University of Basel, Switzerland, where the specific image analysis program (Analyze, v7.4, Biomedical Imaging Resources, Mayo Foundation, Rochester, NY, USA) was made available. Mineralization densitograms of 18 sacroiliac joint dysfunction patients pre- and post-sacroiliac joint arthrodesis (>= 6, >= 12, and >= 24 months post-surgery) were obtained using computed tomography osteoabsorptiometry. For each patient, pre- vs. post-surgery statistical comparisons were undertaken, using the Hounsfield unit values derived from the subchondral mineralization of superior, anterior, and inferior regions on the iliac and sacral auricular surfaces. Post-operative values were also compared to those from a healthy control cohort (n = 39). In the pre-operative cohort at all 3 follow-up times, the superior iliac region showed significantly higher Hounsfield unit values than the corresponding sacral region (P < 0.01). Mineralization comparisons were similar for the sacrum and ilium in the anterior and inferior regions at all follow-up points (P > 0.5) with no surgery-related changes. Sacral density increased significantly in the post-operative state; not observed on the ilium. Post-operative sacroiliac joints showed a significantly increased mineralization in the superior sacrum after >= 6 months (P < 0.05), not replicated after >= 12 nor >= 24 months. Further comparison of post-operative scans versus healthy controls revealed significantly increased mineralization in the superior sacral region at (>=) 6, 12, and 24 months (P < 0.01), likely related to bone grafting, and in the anterior and inferior regions in post-operative scans at >= 12 and >= 24 months follow-up (P < 0.05). The given study is limited in sample size. Post-operative computed tomography scans had screws which may have left artifacts or partial volume effects on the surfaces. Healthy controls were different patients to the sacroiliac joint dysfunction and post-operative cohorts. Both cohorts were age-matched but this comparison did not take into account potential population differences. Size differences in the regions may have also been an influencing factor of the results as the regions were based on the size and shape of the articular surface. Sacroiliac joint arthrodesis results in an increased morpho-mechanical conformity in the anterior and inferior sacrum and reflects variable morpho-mechanical density patterns compared to the healthy state due to permanent alterations in the kinematics of the posterior pelvis.

Brain functions and cognition on transient insulin deprivation in type 1 diabetes

BACKGROUNDType 1 diabetes (T1D) is a risk factor for dementia and structural brain changes. It remains to be determined whether transient insulin deprivation that frequently occurs in insulin-treated individuals with T1D alters brain function.METHODSWe therefore performed functional and structural magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological testing at baseline and following 5.4 ± 0.6 hours of insulin deprivation in 14 individuals with T1D and compared results with those from 14 age-, sex-, and BMI-matched nondiabetic (ND) participants with no interventions.RESULTSInsulin deprivation in T1D increased blood glucose, and β-hydroxybutyrate, while reducing bicarbonate levels. Participants with T1D showed lower baseline brain N-acetyl aspartate and myo-inositol levels but higher cortical fractional anisotropy, suggesting unhealthy neurons and brain microstructure. Although cognitive functions did not differ between participants with T1D and ND participants at baseline, significant changes in fine motor speed as well as attention and short-term memory occurred following insulin deprivation in participants with T1D. Insulin deprivation also reduced brain adenosine triphosphate levels and altered the phosphocreatine/adenosine triphosphate ratio. Baseline differences in functional connectivity in brain regions between participants with T1D and ND participants were noted, and on insulin deprivation further alterations in functional connectivity between regions, especially cortical and hippocampus-caudate regions, were observed. These alterations in functional connectivity correlated to brain metabolites and to changes in cognition.CONCLUSIONTransient insulin deprivation therefore caused alterations in executive aspects of cognitive function concurrent with functional connectivity between memory regions and the sensory cortex. These findings have important clinical implications, as many patients with T1D inadvertently have periods of transient insulin deprivation.TRIAL REGISTRATIONClinicalTrials.gov NCT03392441.FUNDINGClinical and Translational Science Award (UL1 TR002377) from the National Center for Advancing Translational Science; NIH grants (R21 AG60139 and R01 AG62859); the Mayo Foundation.

The mitral annulus disjunction of mitral valve prolapse: presentation and outcome

Abstract Background Mitral-annulus-disjunction (MAD), often described in mitral-valve-prolapse (MVP) patients, remains incompletely defined and its clinical outcome consequences are unknown. Objectives To assess MAD prevalence, clinical and echocardiographic characteristics, and independent impact on outcome in patients with isolated-MVP. Methods A cohort of 595 (65±16 years, 278 female) consecutive patients with MVP and comprehensive clinical, rhythmic and Doppler-echocardiographic characterization, was identified. Primary-endpoint was overall-survival, or occurrence of ventricular-arrhythmia. To eliminate clinical differences, we matched MAD-patients 1:1 with no-MAD based on propensity score for overall survival analysis using a greedy 5-to-1 digit-matching algorithm. Results MAD was frequent, present in 186 (31%) of MVP-patients and independently associated to bileaflet-MVP, leaflet-redundancy, younger-age, female-sex, enlarged left-ventricle-endsystolic-diameter and higher left-ventricle-ejection-fraction (all P≤0.04). Outcome primary-endpoint of survival after MVP diagnosis in matched-cohort (10-year 95±1%) was not associated with MAD presence (10-year 93±2% for no-MAD and 97±1% for MAD, P=0.4). Mortality was comparable for MAD (univariate-hazard-ratio 0.64 [0.25–1.65], P=0.4 vs. no-MAD), even adjusted-comprehensively including for MVP-characteristics (adjusted-hazard-ratio 1.17 [0.39–3.50], P=0.8). However, 220 (51%) MVP-patients were diagnosed ventricular-arrhythmia (161 with ventricular-tachycardia only) and long-term, MAD was associated with lower arrhythmia- and ventricular-tachycardia- overall freedom (adjusted-hazard-ratio for MAD 2.35 [1.75–3.15], P&amp;lt;0.0001 vs. no-MAD and 2.71 [1.93–3.82], P&amp;lt;0.0001 respectively). Hence, 10-year freedom of significant ventricular-arrhythmia in overall-cohort was severely reduced with MAD (41±4% vs. 62±3% for no-MAD). Conclusion In this unique MVP cohort, with arrhythmia and MAD comprehensively-characterized, MAD presence was frequent and independently associated to bileaflet-MVP and leaflet-redundancy. Long-term, MAD compared to no-MAD is not independently associated with higher-mortality but to reduced arrhythmia-freedom occurrence. Survival overall and by V arrhythmia Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Mayo Foundation

Non-invasive vocal biomarker is associated with pulmonary hypertension

Abstract Background Heart failure (HF) is a debilitating disease and is associated with significant morbidity and mortality, and costs to health care systems. Monitoring the impact of therapy remotely holds the potential to reduce HF-related hospitalizations, improve quality of life, and optimize the use of the limited resources. Voice signal is an emerging non-invasive biomarker that has been associated with a number of disease states. We previously identified a significant relationship between specific vocal biomarkers and coronary artery disease, and recently extended these observations by showing that a pre-specified voice biomarker was associated with increased mortality and re-hospitalization in patients with HF. Purpose In the current study, we evaluated the association between a vocal biomarker derived from voice signal analysis and invasively measured indices of pulmonary hypertension (PH). We hypothesized that the pre-specified voice biomarker might be associated with hemodynamic indices reflective of PH that are known to be linked to HF-severity, and that predict outcomes such as HF-related hospitalization and death. Methods The study population included patients referred for an invasive cardiac hemodynamic study between January 2017 and December 2018. Subjects had their voice signal recorded to their smartphone on three separate occasions prior to the cardiac study. A pre-established numeric vocal biomarker was derived from each recording, and the mean vocal biomarker calculated for each patient. Patients were a priori divided into two groups: those with high pulmonary arterial pressure (PAP) defined as ≥35 mmHg consistent with moderate or greater PH, versus those with a lower PAP. Results Eighty three patients, mean age 61.6±15.1 years, 37 (44.6%) male, were included in the study. The intraclass correlation coefficient for the vocal biomarker in all patients was 0.83 implying very good agreement between values. Patients with a high mean PAP (≥35 mmHg) had significantly higher values of the voice biomarker compared to those with a lower mean PAP (0.74±0.85 vs. 0.43±0.86, p=0.008). Patients with a high pulmonary vascular resistance (PVR) defined as a PVR ≥1.7 Wood Units had significantly higher values of the voice biomarker compared to those with a lower PVR (0.62±0.83 vs. 0.33±0.90, p=0.026). Multivariable logistic regression showed that an increase in the voice biomarker by 1 unit was significantly associated with a high PAP, odds ratio (OR) 2.31, 95% CI 1.05–5.07, p=0.038, and with borderline significance with a high PVR, OR 2.14, 95% CI 0.94–4.87, p=0.07. Conclusion The current study shows a relationship between a noninvasive vocal biomarker derived from voice signal analysis and invasively derived hemodynamic indices related to PH obtained during cardiac catheterization. These results may have important and practical clinical implications for telemedicine and remote monitoring of patients with HF and PH. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Mayo Foundation; Beyond Verbal Communications

The top 100 highly cited articles on osteoporosis from 1990 to 2019: a bibliometric and visualized analysis.

To provide a bibliometric and visualized analysis of the top 100 highly cited articles on osteoporosis indexed by the Web of Science (WoS) from 1990 to 2019. Data were obtained from the WoS Core Collection on Jan 10, 2020. Qualitative and quantitative analysis was conducted based on WoS. Collaboration analysis and keywords analysis were performed using VosView software. A total of 12,863 references were obtained. The top 100 highly cited literature included 73 articles and 27 reviews. The average citation number of the 100 articles was 747 (range 370 to 2970). The fund sources mostly came from the USA. A total of 29 journals published the top 100 highly cited literature. The New England Journal of Medicine had the largest number of papers and the highest total cited times. The USA published 72 articles. The University of California San Francisco published 17 articles, followed by University of Sheffield and Mayo Clinic and Mayo Foundation. Cooper C had the most publications (n = 12) and Genant HK had the largest total citation (n = 11,055). Considering only the first author and corresponding author, Kanis JA had published the most articles. Researchers and institutions from the USA, the UK, and France contributed the most to the top high-cited articles. Research on osteoporosis is a well-developed and promising research field. The top 100 articles have been cited widely and actively. New England Journal of Medicine was the most popular journal. The most productive country was the USA. The University of California San Francisco, University of Sheffield, and Mayo Clinic and Mayo Foundation were the most productive institutions. Cooper C, Kanis JA, and Genant HK were the most prolific and influential authors. Researchers and institutions from North America and Europe contributed the most.

Black Dancer by Robert Perless

Rcognizing the contribution art has had in the Mayo Clinic environment since the original Mayo Clinic Building was finished in 1914, Mayo Clinic Proceedings features some of the numerous works of art displayed throughout the buildings and grounds on Mayo Clinic campuses as interpreted by the author.

0799 A Population-based Study of Adult Patients With Recurrent, Clinician Diagnosed Sleepwalking and/or Sleep Related Eating Disorder

Abstract Introduction The ICSD-3 describes NREM-related parasomnias as abnormal sleep related complex movements where motor behavior occurs in the setting of absent or very minimal higher cognitive function. A population-based twin study reported that 3.9% of men and 3.1 % of women sleepwalk (SW) with 30% reported experiencing injury (Hublin 1997). Sleep related eating disorder (SRED) may be a variant of SW with a reported prevalence of 0.5-5 % (Michalska 2016). This study examined SW and SRED in a population-based sample permitting review of associated features, risk factors and outcomes. Methods The records-linkage system of the Rochester Epidemiology Project that includes all adults residing in Olmsted County MN was searched for documentation of patients seeking care for at least two episodes of sleepwalking and/or sleep eating. Records from 2007-2016 were included. Results 56 cases were identified with 50 (89 %) having SW and 16 (29%) SRED. The gender breakdown was 50% male and 50% female with the mean age at diagnosis of 40 (SD 13). Childhood parasomnia events were reported by 23/36 (62%) and a family history in 21/35 (64%). Data were unavailable for the others. The number of parasomnia incidents was ≥ 10 for 21 (37%). A variety of experiences were documented, including leaving the bedroom (39%), injury (25%), and exiting through a window/balcony (5%). Associated factors were sleep deprivation (52%), untreated obstructive sleep apnea (34%), antidepressant use (41%), zolpidem use (18%), circadian disruption (14%) and alcohol use (9%). Polysomnography was conducted for 41 (74%). Documented interventions were medication discontinuation (18%) and starting a benzodiazepine (16%). In 21%, no treatment was given. Conclusion This population-based study of adults with clinician diagnosed recurrent SW and SRED revealed equal rates in men and women. The majority of patients with SRED also had SW. 25% of cases were associated with injuries. Support Rochester Epidemiology Project supported by NIH R01 AG034676 and AG052425 and the Mayo Foundation.