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Surveillance imaging at 45 to 90 days after transcatheter left atrial appendage occlusion device implantation with transesophageal echocardiography (TEE) or cardiac computed tomography (CT) is recommended to assess device position and the presence of device-related complications such as device-related thrombus (DRT) or peridevice leak. Detection of DRT is associated with a significantly increased risk of a stroke or systemic embolization event within 6 months of detection. Nonetheless, there is significant variability in detection of DRT as a result of timing, frequency, and imaging modality used for surveillance. The process of DRT formation vs benign device endothelization is not known. Here we highlight the spectrum of imaging findings seen on TEE and CT and emphasize the need for unified definitions and standardized reporting of imaging findings., Competing Interests: Dr Alkhouli has served on Advisory board for Boston Scientific and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: A subset of individuals with major depressive disorder (MDD) have a high burden of cardiovascular risk factors and cerebral small-vessel disease, implicating vascular disease in the development of depression. Cross-sectional studies demonstrate a link between endothelial dysfunction and MDD, but the prospective association between peripheral endothelial dysfunction (PED) and an incident diagnosis of MDD is unknown., Methods and Results: Patients undergoing a baseline assessment of cardiovascular risk were evaluated for PED using reactive hyperemia-peripheral arterial tonometry (≤1.8 consistent with PED). Patient medical records were reviewed to identify those who underwent a formal clinical evaluation of MDD after the index PED evaluation. The frequency of PED was compared in those with and without MDD. Logistic regression analyses were performed to assess the association between baseline PED and incident MDD. Between January 2006 and December 2020, 1614 patients underwent testing for PED. Four hundred eighty-four (30.1%) patients underwent a formal evaluation for MDD after (0-15 years) the index procedure (mean±SD age, 52.8±13.8 years; 65.2% women). Of these, 157 (32.4%) had PED and 108 (31.0%) were diagnosed with MDD. Individuals with MDD had a higher frequency of PED (40.2% versus 30.2%; P =0.034) compared with those without MDD. In multivariable analyses, PED was significantly associated with MDD (odds ratio, 2.3 [95% CI, 1.4-3.8]; P <0.001)., Conclusions: PED is significantly associated with incident MDD. Thus, PED may be a useful marker to identify individuals at increased risk of depression who may benefit from more frequent and earlier management strategies.

Purpose: Pharmacogenomics is the study of how individual responses to medication are influenced by genetics. As medication experts, pharmacists are uniquely suited to practicing this application of precision medicine. Fundamental operational aspects of developing a pharmacy clinical pharmacogenomics practice are described, and the specific experience of a multisite health system in developing a pharmacogenomics service is discussed., Summary: Considerations for the development of a clinical pharmacy-driven pharmacogenomics service include understanding testing selection, targeting the appropriate patient population, exploration of reimbursement, design of the practice, and education of the pharmacogenomics workforce. Testing can be preemptive or reactive, can occur in house or as a send-out service, and can be panel based or specific to a single gene. Pharmacogenomics is applicable to many medicine specialties, making deployment of services to strategic groups essential. Reimbursement for pharmacogenomics is variable and may pose a barrier to implementation. The demand for pharmacogenomics education for pharmacy students and as a formal postgraduate career path is growing. Pharmacogenomics service planning and implementation details for a multisite health system are described., Conclusion: The practice of pharmacogenomics presents a remarkable opportunity for clinical pharmacists and health systems to improve patient care outcomes and experiences., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Limited data exist on outcomes of atrial fibrillation (AF) catheter ablation based on hospital setting and, specifically, the availability of onsite cardiothoracic surgery (CTS). We aimed to describe the characteristics and outcomes of catheter ablation for AF performed at a facility with and without CTS., Methods: This was a retrospective study of consecutive patients who underwent catheter ablation for AF at hospital with (CTS) and without cardiothoracic surgery (N-CTS) from January 2011 through December 2019. Clinical and procedural characteristics, complications, and 1-year outcomes, including clinical events and AF recurrence, were collected., Results: There were 326 unique patients who underwent an index AF ablation procedure: 206 CTS patients and 120 N-CTS patients. There were no differences in overall cardiac complications (2.5% vs. 5.8%), including mapping catheter entrapment requiring open-heart surgery (0% vs. 0.5%), pericardial effusion requiring pericardiocentesis (0.8% vs. 0.5%), hemopericardium (1.7% vs. 0.5%), acute myocardial infarction (0% vs. 1.0%), and sinus node injury (0% versus 0.5%) (all P values > .05) between N-CTS and CTS patients. Likewise, overall noncardiac complications (20.7% vs. 19.8%, P = .85), including bleeding, cerebrovascular accident, and phrenic or vagus nerve injury, were similar between N-CTS and CTS hospitals. Also, 1-year cumulative Kaplan-Meier estimates of overall AF recurrence (11.6% vs. 16.4%; log-rank P = 0.21; HR 1.47; 95% CI, 0.79-2.74) were not statistically significant between N-CTS and CTS hospitals., Conclusion: Catheter ablation procedure is safe and effective regardless of onsite CTS presence, and there were no significant differences between the two hospital settings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate the diagnostic performance of the previously recommended baseline high-sensitivity cardiac troponin T (hs-cTnT) thresholds of 52 and 100 ng/L in identifying patients at high risk of acute myocardial infarction (AMI)., Patients and Methods: This study compared the positive predictive value (PPV) for index AMI of these high-risk hs-cTnT thresholds in adult patients in the emergency department undergoing hs-cTnT measurement., Results: The adjudicated MAyo Southwest Wisconsin 5th Gen Troponin T ImplementatiON cohort included 2053 patients, with 157 (7.6%) who received a diagnosis of AMI. The hs-cTnT concentrations of greater than 52 and greater than 100 ng/L resulted in PPVs of 41% (95% CI, 35%-48%) and 57% (95% CI, 48%-66%). In patients with chest discomfort, hs-cTnT concentrations greater than 52 ng/L resulted in a PPV of 66% (95% CI, 56%-76%) and hs-cTnT concentrations greater than 100 ng/L resulted in a PPV of 77% (95% CI, 65%-87%). The CV Data Mart Biomarker cohort included 143,709 patients, and 3003 (2.1%) received a diagnosis of AMI. Baseline hs-cTnT concentrations greater than 52 and greater than 100 ng/L resulted in PPVs of 12% (95% CI, 11%-12%) and 17% (95% CI, 17%-19%), respectively. In patients with chest pain and hs-cTnT concentrations greater than 52 ng/L, the PPV for MI was 17% (95% CI, 15%-18%) and in those with concentrations greater than 100 ng/L, only 22% (95% CI, 19%-25%)., Conclusion: In unselected patients undergoing hs-cTnT measurement, the hs-cTnT thresholds of greater than 52 and greater than 100 ng/L provide suboptimal performance for identifying high-risk patients. In patients with chest discomfort, an hs-cTnT concentration of greater than 100 ng/L, but not the European Society of Cardiology-recommended threshold of greater than 52 ng/L, provides an acceptable performance but should be used only with other clinical features., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Aims: Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as they often have increased high-sensitivity cardiac troponin T (hs-cTnT) concentrations., Methods and Results: Observational US cohort study of emergency department patients undergoing hs-cTnT measurement. Cases with ≥1 hs-cTnT increase > 99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2 h hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2). The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 75 (15%) and 350 (70%) patients with CKD and 80 (5%) and 351 (24%) without CKD who had acute MI and myocardial injury. In CKD patients with baseline hs-cTnT thresholds of ≥52, >100, >200, or >300 ng/L, positive predictive values (PPVs) for MI were 36% (95% CI 28-45), 53% (95% CI 39-67), 73% (95% CI 50-89), and 80% (95% CI 44-98), and in those without CKD, 61% (95% CI 47-73), 69% (95% CI 49-85), 59% (95% CI 33-82), and 54% (95% CI 25-81). In CKD patients with a 2 h hs-cTnT delta of ≥10, >20, or >30 ng/L, PPVs were 66% (95% CI 51-79), 86% (95% CI 68-96), and 88% (95% CI 68-97), and in those without CKD, 64% (95% CI 50-76), 73% (95% CI 57-86), and 75% (95% CI 58-88)., Conclusion: Diagnostic performance of standard baseline and serial 2 h hs-cTnT thresholds to rule-in MI is suboptimal in CKD patients. It significantly improves when using higher baseline thresholds and delta values., Competing Interests: Conflict of interest: A.S.J. has consulted or presently consults for most of the major diagnostics companies, including Beckman-Coulter, Abbott, Siemens, ET Healthcare, Ortho Diagnostics, Roche, Radiometer, Sphingotec, Spinchip, and LumiraDx. He has stock in RCE Technologies. Y.S. has been on advisory boards or consults for Roche Diagnostics, Abbott. Diagnostics, Philips, GE, and Zoll. All other authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: The purpose of this study is to evaluate the association between hyperparathyroidism (PHPT), parathyroid hormone levels, and calcium levels in patients diagnosed with benign fibro-osseous lesions such as fibrous dysplasia (FD), ossifying fibroma (OF), central giant cell granulomas (GCG)., Methods: This is a retrospective, single-center study from a sample of patients who underwent surgical treatment of FD, OF, and GCG at Mayo Clinic between 1996 and 2021. Patient demographics, history of PHPT, histopathological diagnosis, and relevant laboratory values such as parathyroid hormone (PTH), serum calcium, vitamin D, and alkaline phosphatase were collected., Results: Of the patients diagnosed with FD (n = 64), OF (n = 24), and GCG (n = 5), a diagnosis of PHPT was found in 2 patients (3.1%), 1 patient (4.2%), and 0 patients (0%), respectively. Elevated PTH levels (>65 pg/mL) were observed in 3 patients (4.7%) with FD, 1 patient (4.2%) with OF, and 1 patient (20%) with GCG. Mean (standard deviation) calcium levels were 9.3 (0.6) mg/dL in the FD group, 9.4 (0.5) mg/dL in the OF group, and 9.3 (0.6) mg/dL in the GCG group. Patients with fibro-osseous jaw tumors including FD, OF, and GCG may have increased risk of PHPT compared to the general population., Conclusion: Patients with benign jaw tumors including FD, OF, and GCG may have increased risk of PHPT compared to the general population. Surgeons treating these benign tumors need to be cognizant of these findings, obtain appropriate laboratory studies, and incorporate multidisciplinary care including endocrinologists, endocrine surgeons, and maxillofacial surgeons., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The management of pulmonary embolus and intracardiac masses is rapidly evolving with the availability of transcatheter aspiration devices. We describe the utility of a transcatheter aspiration device in management of a patient with pulmonary embolus and a right atrial mass in transit after spinal surgery where a topical hemostatic agent was used to control intraoperative bleeding., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Loneliness and social isolation are associated with poor health outcomes such as an increased risk of cardiovascular diseases., Objectives: The authors aimed to explore the association between social isolation with biological aging which was determined by artificial intelligence-enabled electrocardiography (AI-ECG) as well as the risk of all-cause mortality., Methods: The study included adults aged ≥18 years seen at Mayo Clinic from 2019 to 2022 who respond to a survey for social isolation assessment and had a 12-lead ECG within 1 year of completing the questionnaire. Biological age was determined from ECGs using a previously developed and validated convolutional neural network (AI-ECG age). Age-Gap was defined as AI-ECG age minus chronological age, where positive values reflect an older-than-expected age. The status of social isolation was measured by the previously validated multiple-choice questions based on Social Network Index (SNI) with score ranges between 0 (most isolated) and 4 (least isolated)., Results: A total of 280,324 subjects were included (chronological age 59.8 ± 16.4 years, 50.9% female). The mean Age-Gap was -0.2 ± 9.16 years. A higher SNI was associated with a lower Age-Gap (β of SNI = 4 was -0.11; 95% CI: -0.22 to -0.01; P  < 0.001, adjusted to covariates). Cox proportional hazard analysis revealed the association between social connection and all-cause mortality (HR for SNI = 4, 0.47; 95% CI: 0.43-0.5; P  < 0.001)., Conclusions: Social isolation is associated with accelerating biological aging and all-cause mortality independent of conventional cardiovascular risk factors. This observation underscores the need to address social connection as a health care determinant., Competing Interests: Drs Friedman, Lopez-Jimenez, and Attia are coinvestigators of the AI-ECG age algorithm, which has been licensed to Alumana, Mayo Clinic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Purpose: External beam radiation therapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, the Barcelona Clinic Liver Cancer system does not recommend the use of EBRT in HCC due to a lack of sufficient evidence and intends to perform an individual patient level meta-analysis of ablative EBRT in this population. However, there are many types of EBRT described in the literature with no formal definition of what constitutes "ablative." Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC., Methods and Materials: Fundamental parameters related to dose, fractionation, radiobiology, target identification, and delivery technique were identified by a steering committee to generate 7 Key Criteria (KC) that would define ablative EBRT for HCC. Using a modified Delphi (mDelphi) method, experts in the use of EBRT in the treatment of HCC were surveyed. Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of ≥70% was used to define consensus for answers to each KC., Results: Of 40 invitations extended, 35 (88%) returned responses. In the first round, 3 of 7 KC reached consensus. In the second round, 100% returned responses and consensus was reached in 3 of the remaining 4 KC. The distribution of answers for one KC, which queried the a/b ratio of HCC, was such that consensus was not achieved. Based on this analysis, ablative EBRT for HCC was defined as a BED10 ≥80 Gy with daily imaging and multiphasic contrast used for target delineation. Treatment breaks (eg, for adaptive EBRT) are allowed, but the total treatment time should be ≤6 weeks. Equivalent dose when treating with protons should use a conversion factor of 1.1, but there is no single conversion factor for carbon ions., Conclusions: Using a mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empirical data are required to define the a/b of HCC., Competing Interests: Disclosures Ted K. Yanagihara reports grants or contracts from the Radiation Oncology Institute and Lineberger Comprehensive Cancer Center; serving as an expert independent reviewer for the North Carolina Medical Board; and serving as an American Board of Radiology Maintenance of Certification online longitudinal assessment senior reviewer. Andrew M. Moon reports grants or contracts from the American Association for the Study of Liver Diseases, the American College of Gastroenterology, and the National Institutes of Health; consulting feeds from Target RWE; and serving on the American Association for the Study of Liver Diseases Practice Guidelines Committee. Aisling Barry reports honoria from Eisai. Ferran Torres reports grants or contracts from the Hospital Clinic Barcelona (IDIBAPS); consulting fees from Universal DX; and participation in the data safety monitoring board/advisory board of the Hospital Clinic Barcelona with partial support from Bayer. Daniel T. Chang reports grants or contracts from RefleXion Medical, ViewRay, Inc, Varian Medical Systems; honoraria for presentation from Varian Medical Systems; support for attending meetings and travel from Varian Medical Systems; and participation on data safety monitoring board for the SMART trial for ViewRay. Chandan Guha reports grants or contracts from the NIH, Janssen and Celldex; consulting fees from Janssen; participation in the data safety monitoring board or advisory board of the Focused Ultrasound Foundation; and is a founder of BioConvergent Health. Morten Hoyer reports honoraria from Novo Nordisk. Lisa Kachnic reports receiving grants or contracts from Varian Medical Systems; serving as an editor for UpToDate; participation on the data safety monitoring committee for Beta Innovations; and is a board member of the Radiation Therapy Oncology Group. Eugene J. Koay reports funding from the Department of Defense and National Institutes of Health; grants or contracts from Philips Healthcare, GE Healthcare, Stand up to Cancer, Project Purple, Elekta, Department of Defense; royalties from Taylor and Francis, LLC; consulting fees from RenovoRx, AstraZeneca, Augmenix, and Kallisio; honoraria for lectures from Apollo Cancer hospitals in Chnnai India, Bayer Healthcare, Philips Healthcare, and Aptitude Health; a patent pending for 3-dimensional printed oral stents; serving on the scientific medical advisory board of the International Cholangiocarcinoma Research Network; and stock ownership of Quantum Aurea Capital. Joel Mases reports grants or contracts from Boston Scientific and royalties or licenses from Springer and UpToDate. Pablo Munoz-Schuffenegger reports grants or contracts from the National Fund for Scientific and Technological Development, National Commission for Scientific and Technological Research, Government of Chile; honoraria for lectures from Bayer and Roche Pharma AG; serving on an advisory board for AstraZeneca; and serving on the advanced radiation therapy committee, International Association for the Study of Lung Cancer. Dawn Owen reports payment from UpToDate and receipt of goods/services from AstraZeneca and Varian Medical Systems. Marta Scorsetti reports grants or contracts from Varian Medical Systems, Sofar, and IPSEN. Jenniefer Y. Wo reports grants or contracts from Genentech. Maria Reig reports grants or contracts from Bayer, Ipsen, and ISCII; serving as a consultant or on advisory boards and/or receiving travel support from Bayer, BMS, Roche, Ipsen, AstraZeneca, Eisai, Geneos Therapeutics, UniveralDx, MSD and Lilly; receiving lecture fees from Bayer, BMS, Gilead, AstraZeneca, ROCHE and Lilly; receiving support for attending meetings and/or travel from Bayer, BMS, Roche, Ipsen, AstraZeneca, Eisai, MSD, and Lilly; and serving as EASL representative in UEG. Laura A. Dawson reports serving as chair of ASTRO., (Copyright © 2023. Published by Elsevier Inc.)

Cardiovascular disease is often a disease of aging. Considerable advances in our understanding of the biological mechanisms of aging have been made; yet, cardiovascular disease remains the leading cause of death in the United States urging a continued search for novel risk factors to target for preventing and treating disease. Mental stress (MS) is emerging as an important risk factor, and while progress has been made in understanding the link between MS and cardiovascular disease, the precise mechanisms of a putative causal relationship require greater clarification. In the current review, we (1) summarize our current understanding of the pathological effects of MS on vascular health; (2) describe important aspects of the pathobiology of vascular aging including inflammation, oxidative stress, mitochondrial dysfunction as well as novel processes such as genomic instability, epigenetic alterations, and nutrient signal pathways; (3) highlight similarities in the downstream biologic effects of aging and MS on vascular health with an emphasis on cellular and molecular processes that could be used to develop novel prognostic markers and treatment strategies for cardiovascular disease; (4) discuss lifestyle and pharmacological methods that target indicators of aging whose role could be translated into approaches managing the effects of MS; and (5) outline important future steps that should be considered in this area of research including the need for prospective clinical trials and for creating greater collaboration between preclinical aging researchers and clinical investigators managing MS., Competing Interests: Disclosures None.

Witkop tooth and nail syndrome is a rare, autosomal dominant type of ectodermal dysplasia that can have significant effects on dentition, including hypoplastic and malformed dentition and significantly atrophic maxillas. Endosseous implants have become one possible solution to replace missing teeth, although their use in areas where bone is sparse becomes challenging. Due to the severe atrophy of the maxillary alveolus, extensive preprosthetic surgeries including orthognathic surgery, extensive bone grafting, and sinus floor augmentations have been recommended prior to placement of endosseous dental implants. Although this treatment has shown favorable outcomes, it requires multiple surgical procedures, contributing to a prolonged treatment course and increased morbidity. An alternative treatment of atrophic maxillas in patients with ectodermal dysplasia includes the use of zygomatic implants. This familial case series discusses 3 siblings, all previously diagnosed with Witkop Syndrome, who underwent comprehensive preprosthetic surgery and prosthetic rehabilitation using zygomatic implants with a follow-up period up to 15 years., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Spontaneous coronary artery dissection (SCAD) is an epicardial coronary artery dissection not associated with atherosclerosis or trauma, and is not iatrogenic. The pathogenesis of SCAD is not fully understood, and the association of coronary artery anomalies and SCAD is not known. We present a case of a 64-year-old woman presenting with non-ST-elevation myocardial infarction (NSTEMI) due to have multivessel SCAD in the setting of anomalous origin of the coronary arteries with all three coronary arteries - right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCx) originating from the right sinus of Valsalva., Learning Points: Spontaneous coronary artery dissection (SCAD) and coronary artery anomaly can arise where all three arteries originate from the right coronary cusp;There are possible associations between SCAD and coronary artery anomalies;Treatment and management of multivessel SCAD with a coronary artery anomaly where all three arteries arise from the right sinus of Valsalva., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2023.)

Background: The 2021 American College of Cardiology/American Heart Association chest pain guidelines recommend risk scores such as HEAR (History, Electrocardiogram, Age, Risk factors) for short-term risk stratification, yet limited data exist integrating them with high-sensitivity cardiac troponin T (hs-cTnT)., Methods: Retrospective, multicenter (n = 2), observational, US cohort study of consecutive emergency department patients without ST-elevation myocardial infarction who had at least one hs-cTnT (limit of quantitation [LoQ] <6 ng/L, and sex-specific 99th percentiles of 10 ng/L for women and 15 ng/L for men) measurement on clinical indications in whom HEAR scores (0-8) were calculated. The composite major adverse cardiovascular event (MACE) outcome was 30-day prognosis., Results: Among 1979 emergency department patients undergoing hs-cTnT measurement, 1045 (53%) were low risk (0-3), 914 (46%) intermediate risk (4-6), and 20 (1%) high risk (7-8) based on HEAR scores. HEAR scores were not associated with increased risk of 30-day MACE in adjusted analyses. Patients with quantifiable hs-cTnT (LoQ-99th) had an increased risk for 30-day MACE (3.4%) irrespective of HEAR scores. Those with serial hs-cTnT <99th percentile remained at low risk (range 0%-1.2%) across all HEAR score strata. Higher scores were not associated with long-term (2-year) events., Conclusions: HEAR scores are of limited value in those with baseline hs-cTnT 99 th percentile to define short-term prognosis. In those with baseline quantifiable hs-cTnT within the reference range (<99 th percentile), a higher risk (>1%) for 30-day MACE exists even in those with low HEAR scores. With serial hs-cTnT measurements, HEAR scores overestimate risk when hs-cTnT remains <99th percentile., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Transcatheter tricuspid valve edge-to-edge repair (TTEER) is associated with improvement in outcomes for symptomatic patients with severe tricuspid regurgitation (TR). However, reliable predictors for clinical success are not yet fully defined. This study aims to describe right heart catheterization (RHC) findings in patients referred for TTEER and identify hemodynamic characteristics of patients who experience immediate symptomatic improvement following successful TR intervention., Methods: Patients who underwent TTEER and had a separate RHC within the preceding 6 months were included. Hemodynamic tracings from the RHC and TTEER procedures were reviewed and recorded. Clinical success was defined as a successful device implant with at least 1-grade of TR reduction and improvement in NYHA class by 1 or more grades on 30-day echocardiogram and clinical follow-up., Results: Thirteen patients underwent an RHC within 6 months of TTEER procedure (median age 76 years [IQR: 73-80]). All patients were on a stable dose of loop diuretics. Baseline right atrial pressure was severely elevated (mean 19 mmHg [IQR: 9-24 mmHg]) with prominent CV waves. Median pulmonary capillary wedge pressure (PCWP) was 20 mmHg (IQR: 14-22) and 70% of patients had a mean PCWP > 15 mmHg at rest. Median PCWP CV-wave was 34 mmHg (IQR: 23-42). Higher PCWP CV-wave height (40 mmHg [IQR 33-43] versus 18 mmHg [IQR 17-31]) was associated with lower likelihood of clinical success (OR 0.83, 95% CI: 0.35-0.97, p = 0.04)., Conclusions: Inclusion of invasive hemodynamics as part of pre-TTEER evaluation may allow for improved TR phenotyping and patient selection. Patients with a large left atrial CV wave on resting RHC were less likely to experience immediate symptomatic improvement despite procedural success with TTEER., (© 2023 Wiley Periodicals LLC.)

Background: The outcomes of catheter ablation for atrial fibrillation in adults with congenital heart disease are not well described., Methods: In a retrospective study of adult patients with congenital heart disease who underwent catheter ablation for atrial fibrillation between 2000 and 2020 at Mayo Clinic, procedural characteristics and outcomes were collected. The primary outcomes were atrial arrhythmia (AA) recurrence following a 3-month blanking period and repeat ablation. An arrhythmia clinical severity score was assessed pre- and post-ablation based on the duration of arrhythmia episodes, symptoms, cardioversion frequency, and antiarrhythmic drug use., Results: One hundred forty-five patients (age, 57±12 years; 28% female; 63% paroxysmal atrial fibrillation) underwent 198 ablations with a median follow-up of 26 months (interquartile range, 14-69). One hundred ten, 26, and 9 patients had simple, moderate, and complex congenital heart disease, respectively. All patients underwent pulmonary vein isolation, and non-pulmonary vein targets were ablated in 79 (54%). AA recurrence at 12 months was 37% (95% CI, 29%-45%). On univariate analysis, increasing left atrial volume index was associated with higher odds of AA recurrence (odds ratio, 1.03 [1.00-1.06] per 1 mL/m 2 increment; P =0.05). Noninducibility of atrial flutter was predictive of decreased odds of AA recurrence (odds ratio, 0.43 [0.21-0.90]; P =0.03). A second ablation was performed in 43 patients after a median of 20 (interquartile range, 8-37) months. Arrhythmia clinical severity scores improved following ablation, reflecting a decrease in symptoms, cardioversions, and antiarrhythmic drugs., Conclusions: Catheter ablation of atrial fibrillation is feasible and effective in patients with adult congenital heart disease and reduces symptoms. Recurrence of AA frequently requires repeat ablation., Competing Interests: Disclosures Dr Madhavan receives research funding from Boston Scientific, BMS/Pfizer, and Convatec, Inc; speaker honorarium from Biosense Webster; and she is on the steering committee of CERTITUDE Registry, Biotronik, Inc. Dr Asirvatham receives speaking/honoraria from Abbott, Biosense Webster, Biotronik, Boston Scientific, Medtronic, and Zoll. All other authors have no conflicts to disclose.

Competing Interests: Conflict of interest: None declared.

Background: Differentiating type 2 myocardial infarction from myocardial injury can be difficult. In addition, the presence of objective evidence of myocardial ischemia may facilitate identification of high-risk type 2 myocardial infarction patients., Methods: This was an observational cohort study of adult emergency department patients undergoing high-sensitivity cardiac troponin T (hs-cTnT) measurement. Patients with ≥1 hs-cTnT >99th percentile were adjudicated following the Fourth Universal Definition of Myocardial Infarction. Patients were categorized as "subjective type 2 myocardial infarction" when ischemic symptoms were the lone criteria supporting type 2 myocardial infarction, or "objective type 2 myocardial infarction" when there was ≥1 objective clinical feature (electrocardiography, imaging, angiography) of acute myocardial ischemia. The primary outcome was mortality., Results: A total of 857 patients were included, among which 55 (6.4%) were classified as subjective type 2 myocardial infarction, 36 (4.2%) as objective type 2 myocardial infarction, and 702 (82%) as myocardial injury. Those with objective type 2 myocardial infarction had a higher risk of mortality during the index presentation (17% vs 1.7%, P < .0001; hazard ratio 11.1; 95% confidence interval, 3.7-33.4) and at 2-year follow-up (47% vs 31%, P = .04; hazard ratio 1.92; 95% confidence interval, 1.17-3.14) than those with myocardial injury. Objective type 2 myocardial infarction had a higher mortality than subjective type 2 myocardial infarction at index presentation (17% vs 2.0%, P = .01) and at 1 (25% vs 9.1%, P = .04) and 3 months (31% vs 13%, P = .04) follow-up. There were no mortality differences between subjective type 2 myocardial infarction and myocardial injury., Conclusion: In patients diagnosed with type 2 myocardial infarction, those with objective evidence of myocardial ischemia have significantly worse outcomes compared with those with myocardial injury and subjective type 2 myocardial infarction. A more rigorous type 2 myocardial infarction definition that emphasizes these criteria may facilitate diagnosis and risk-stratification., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Recognition and evaluation of structural heart disease has become more common in clinical practice and will continue to grow as the population ages. With the growing availability of surgical and transcatheter interventional options, appropriate evaluation and patient selection for therapy is required. While echocardiography can frequently provide the required anatomic and hemodynamic information required to guide therapeutic decisions, there remains subsets of patients in which noninvasive testing yields inconclusive results prompting the need for invasive hemodynamics., Areas Covered: This article reviews the indications and strengths of invasive hemodynamics in a variety of structural heart diseases. We describe the utilization and benefits of continuous hemodynamics during transcatheter interventions and review the prognostic information that can be gleaned from changes in hemodynamics after intervention., Expert Opinion: The advancement of transcatheter therapies for structural heart disease has sparked a renewed interest in the utilization of invasive hemodynamics. Continued growth and accessibility of comprehensive hemodynamics for clinical practice will rely on clinicians to continually review, refine, and develop procedural techniques beyond the current training standards in order to further advance the field.

Obesity remains a major public health problem, affecting almost half of adults in the United States. Increased risk of cardiovascular disease (CVD) and CVD mortality are major obesity-related complications, and management guidelines now recommend weight loss as a key strategy for the primary prevention of CVD in patients with overweight or obesity. The recently demonstrated efficacy of some pharmacologic therapies for chronic weight management may encourage health care professionals to recognize obesity as a treatable serious chronic disease and motivate patients to re-engage with weight loss when previous attempts have been ineffective or unsustainable. This review article summarizes the benefits and challenges associated with lifestyle changes, bariatric surgery, and historical pharmacologic interventions in the treatment of obesity, and focuses on the current evidence for the efficacy and safety of the newer glucagon-like peptide-1 receptor agonist medications in the management of obesity and potential reduction of CVD risk. We conclude that the available evidence demonstrates glucagon-like peptide-1 receptor agonists should be strongly considered in clinical practice for the treatment of obesity and reduction of CVD risk in people with type 2 diabetes. If ongoing research proves glucagon-like peptide-1 receptor agonists to be effective in reducing the risk of CVD onset in patients with obesity, irrespective of type 2 diabetes status, it will herald a new treatment paradigm in this setting, and now is the time for health care professionals to better recognize the benefits of these agents.

Transapical puncture for transcatheter treatment of mitral-paravalvular leak (PVL) is associated with increased risks even when the apical tract is closed with vascular plugs. A novel technique that leverages back wall support from the right or left atrium can be used to facilitate transcatheter closure of mitral PVL through an antegrade approach. ( Level of Difficulty: Advanced. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Spontaneous coronary artery dissection of the septal arteries is rare and may be overlooked on coronary angiogram. Additionally, dedicated intracoronary imaging may not be feasible due to artery size. Cardiac magnetic resonance imaging has an emerging role in diagnosis, which is critical because management changes significantly if spontaneous coronary artery dissection is diagnosed. ( Level of Difficulty: Beginner. )., Competing Interests: Dr Tweet is supported by funding from the National Institutes of Health (1K23HL155506-01A1). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Whole-Body Electromyostimulation (WB-EMS) is a training technology that enables simultaneous stimulation of all the main muscle groups with a specific impulse intensity for each electrode. The corresponding time-efficiency and joint-friendliness of WB-EMS may be particularly attractive for people unable or unmotivated to conduct (intense) conventional training protocols. However, due to the enormous metabolic and musculoskeletal impact of WB-EMS, particular attention must be paid to the application of this technology. In the past, several scientific and newspaper articles reported severe adverse effects of WB-EMS. To increase the safety of commercial non-medical WB-EMS application, recommendations "for safe and effective whole-body electromyostimulation" were launched in 2016. However, new developments and trends require an update of these recommendations to incorporate more international expertise with demonstrated experience in the application of WB-EMS. The new version of these consensus-based recommendations has been structured into 1) "general aspects of WB-EMS", 2) "preparation for training", recommendations for the 3) "WB-EMS application" itself and 4) "safety aspects during and after training". Key topics particularly addressed are 1) consistent and close supervision of WB-EMS application, 2) mandatory qualification of WB-EMS trainers, 3) anamnesis and corresponding consideration of contraindications prior to WB-EMS, 4) the participant's proper preparation for the session, 5) careful preparation of the WB-EMS novice, 6) appropriate regeneration periods between WB-EMS sessions and 7) continuous interaction between trainer and participant at a close physical distance. In summary, we are convinced that the present guideline will contribute to greater safety and effectiveness in the area of non-medical commercial WB-EMS application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kemmler, Fröhlich, Ludwig, Eifler, von Stengel, Willert, Teschler, Weissenfels, Kleinöder, Micke, Wirtz, Zinner, Filipovic, Wegener, Berger, Evangelista, D’Ottavio, Sara, Lerman, Perez de Arrilucea Le Floc’h, Carle-Calo, Guitierrez and Amaro-Gahete.)

Aims: Our goal was to evaluate a previously validated artificial intelligence-augmented electrocardiography (AI-ECG) screening tool for left ventricular systolic dysfunction (LVSD) in patients undergoing high-sensitivity-cardiac troponin T (hs-cTnT)., Methods and Results: Retrospective application of AI-ECG for LVSD in emergency department (ED) patients undergoing hs-cTnT. AI-ECG scores (0-1) for probability of LVSD (left ventricular ejection fraction ≤ 35%) were obtained. An AI-ECG score ≥0.256 indicates a positive screen. The primary endpoint was a composite of post-discharge major adverse cardiovascular events (MACEs) at two years follow-up. Among 1977 patients, 248 (13%) had a positive AI-ECG. When compared with patients with a negative AI-ECG, those with a positive AI-ECG had a higher risk for MACE [48 vs. 21%, P < 0.0001, adjusted hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.11-1.75]. This was largely because of a higher rate of deaths (32 vs. 14%, P < 0.0001; adjusted HR 1.26, 95% 0.95-1.66) and heart failure hospitalizations (26 vs. 6.1%, P < 0.001; adjusted HR 1.75, 95% CI 1.25-2.45). Together, hs-cTnT and AI-ECG resulted in the following MACE rates and adjusted HRs: hs-cTnT < 99th percentile and negative AI-ECG: 116/1176 (11%; reference), hs-cTnT < 99th percentile and positive AI-ECG: 28/107 (26%; adjusted HR 1.54, 95% CI 1.01-2.36), hs-cTnT > 99th percentile and negative AI-ECG: 233/553 (42%; adjusted HR 2.12, 95% CI 1.66, 2.70), and hs-cTnT > 99th percentile and positive AI-ECG: 91/141 (65%; adjusted HR 2.83, 95% CI 2.06, 3.87)., Conclusion: Among ED patients evaluated with hs-cTnT, a positive AI-ECG for LVSD identifies patients at high risk for MACE. The conjoint use of hs-cTnT and AI-ECG facilitates risk stratification., Competing Interests: Conflict of interest: Y.S.: advisory board/speaker for Roche Diagnostics and advisory board Abbott Diagnostics. Patent #20210401347. A.S.J. has consulted or presently consults for most of the major diagnostics companies, including Beckman-Coulter, Abbott, Siemens, ET Healthcare, Ortho Diagnostics, Roche, Radiometer, Sphingotec, RCE Technologies, and Amgen and Novartis. All other authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Despite advances in endoscopic therapies, malignancy-related GI bleeding remains difficult to manage with high rates of treatment failure and rebleeding. Topical hemostatic agents (THAs) are easier to apply to the wide bleeding surface of tumors. We conducted this systematic review and meta-analysis to evaluate the efficacy of THAs in malignancy-related GI bleeding., Methods: We conducted a comprehensive search of multiple electronic databases to identify studies reporting on the use of THAs in malignancy-related GI bleeding. The primary outcome was the achievement of hemostasis; secondary outcomes were early rebleeding (≤3 days), delayed rebleeding (>3 days), aggregate rebleeding, all-cause mortality, and GI bleeding-related mortality. A meta-analysis of proportions was done for all outcomes., Results: Out of 355 citations, 16 studies with 530 patients were included. Primary hemostasis was achieved in 94.1% (95% confidence interval [CI], 91.5-96.0). Early rebleeding was seen in 13.9% (95% CI, 9.7-19.4) and delayed rebleeding in 11.4% (95% CI, 5.8-21.1). Aggregate rebleeding was seen in 24.2% (95% CI, 18.5-31.0). All-cause mortality was 33.1% (95% CI, 23.7-44.0), whereas GI bleeding-related mortality occurred in 5.9% (95% CI, 2.2%-14.8)., Conclusions: THAs are highly effective for achieving primary hemostasis in malignancy-related GI bleeding. It should be considered as an alternative to traditional endotherapy methods in malignancy-related GI bleeding. Future studies should be designed to evaluate its efficacy and safety as a primary method of hemostasis as compared with traditional endotherapy measures., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Purpose: In patients with malignant oral disease, there is concern that immediate implant placement at the time of ablative and microvascular free flap surgery can contribute to tumor recurrence or delay the diagnosis of recurrence. The purpose of this study is to 1) estimate the incidence of recurrence in patients with malignant disease treated with immediate microvascular free flap reconstruction, endosseous implants, and an oral prosthesis, 2) measure and compare the timing of implant placement, immediate versus delayed, and the time to complete oral rehabilitation, and 3) measure the association between the timing of implant placement and tumor recurrence., Materials and Methods: This is a retrospective cohort study utilizing medical record analysis involving patients with malignant oral cancer undergoing tumor resection and immediate microvascular reconstruction from 1996 to 2019 at the Mayo Clinic, Rochester, MN by the Division of Oral and Maxillofacial Surgery. Additional inclusion criteria comprised of immediate or delayed endosseous implant placement, the fabrication of an oral prosthesis, and a minimum of 2-year follow-up. Data on patient demographics, tumor characteristics, timing of implant placement and prosthesis loading, type of prosthesis, tumor recurrence, or second primary tumor events were analyzed., Results: Thirty-three patients with a mean follow-up of 6.4 years were included. Twenty-four patients (72.7%) were diagnosed with squamous cell carcinoma with 3 patients experiencing tumor recurrence. Fifteen patients had immediate implant placement while 18 patients had delayed implant placement. The mean number of days to prosthetic loading of the implants was 680.4 days and 330.1 days for the delayed implant group and immediate implant group, respectively, which was statistically significant (P = .004). The timing of implant placement and the event of a recurrence were not statistically significant (P = .075)., Conclusion: The incidence of recurrence in patients with malignant oral cancer treated with microvascular reconstruction, endosseous implants, and an oral prosthesis was 12.5% with one recurrence occurring beneath the oral prosthesis. Delayed implant placement resulted in a statistically significant delay in the completion of oral rehabilitation compared to immediate implant placement. There was no difference in the incidence of recurrence in the immediate implant group compared to the delayed implant group., (Copyright © 2022 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Virtual surgical planning (VSP) and three-dimensional (3D) printing have become a standard of care at our institution, transforming the surgical care of complex patients. Patient-specific, anatomic models and surgical guides are clinically used to improve multidisciplinary communication, presurgical planning, intraoperative guidance, and the patient informed consent. Recent innovations have allowed both VSP and 3D printing to become more accessible to various sized hospital systems. Insourcing such work has several advantages including quicker turnaround times and increased innovation through collaborative multidisciplinary teams. Centralizing 3D printing programs at the point-of-care provides a greater cost-efficient investment for institutions. The following article will detail capital equipment needs, institutional structure, operational personnel, and other considerations necessary in the establishment of a POC manufacturing program., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Aims: Limited US outcome data exist among patients with myocardial injury and types 1 and 2 myocardial infarction (MI) evaluated with high-sensitivity cardiac troponin (hs-cTn)., Methods and Results: This is an observational US cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with ≥1 hs-cTnT increase >99th percentile were adjudicated following the Fourth Universal Definition of MI. Post-discharge major adverse cardiovascular events (MACE) included death, MI, heart failure (HF) hospitalization, stroke or transient ischaemic attack, and new-onset atrial fibrillation or flutter during 2 years follow-up. Among 2002 patients, 857 (43%) had ≥1 hs-cTnT >99th percentile. Among these, 702 (81.9%) had myocardial injury, 64 (7.5%) had type 1 MI, and 91 (10.6%) had type 2 MI. Compared with patients without myocardial injury, type 2 MI [8.4 vs. 50%; adjusted hazard ratio (HR) 2.31, 95% confidence interval (CI) 1.49-3.58] and myocardial injury (8.4 vs. 47%; adjusted HR 3.13, 95% CI 2.39-4.09) had a higher risk of MACE, in large part because of death and HF hospitalizations. Compared with patients with type 1 MI, type 2 MI (23 vs. 50%; adjusted HR 2.24; 95% CI 1.23-4.10) and myocardial injury (23 vs. 47%; adjusted HR 2.02; 95% CI 1.20-3.40) also have a higher risk of MACE., Conclusion: Among unselected US ED patients undergoing hs-cTnT measurement, most increases are due to myocardial injury, and type 2 MI is more frequent than type 1 MI. Patients with myocardial injury and type 2 MI have morbid outcomes, in large part due to death and HF., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Circulating tumor DNA (ctDNA), the tumor-derived cell-free DNA fragments in the bloodstream carrying tumor-specific genetic and epigenetic alterations, represents an emerging novel tool for minimal residual disease (MRD) assessment in patients with resected colorectal cancer (CRC). For many decades, precise risk-stratification following curative-intent colorectal surgery has remained an enduring challenge. The current risk stratification strategy relies on clinicopathologic characteristics of the tumors that lacks precision and results in over-and undertreatment in a significant proportion of patients. Consequently, a biomarker that can reliably identify patients harboring MRD would be of critical importance in refining patient selection for adjuvant therapy. Several prospective cohort studies have provided compelling data suggesting that ctDNA could be a robust biomarker for MRD that outperforms all existing clinicopathologic criteria. Numerous clinical trials are currently underway to validate the ctDNA-guided MRD assessment and adjuvant treatment strategies. Once validated, the ctDNA technology will likely transform the adjuvant therapy paradigm of colorectal cancer, supporting ctDNA-guided treatment escalation and de-escalation. The current article presents a comprehensive overview of the published studies supporting the utility of ctDNA for MRD assessment in patients with CRC. We also discuss ongoing ctDNA-guided adjuvant clinical trials that will likely shape future adjuvant therapy strategies for patients with CRC.

Background: There are good data to support using a single high-sensitivity cardiac troponin T (hs-cTnT) below the limit of detection of 5 ng/L to exclude acute myocardial infarction. Per the US Food and Drug Administration, hs-cTnT can only report to the limit of quantitation of 6 ng/L, a threshold for which there are limited data. Our goal was to determine whether a single hs-cTnT below the limit of quantitation of 6 ng/L is a safe strategy to identify patients at low risk for acute myocardial injury and infarction., Methods: The efficacy (proportion identified as low risk based on baseline hs-cTnT<6 ng/L) of identifying low-risk patients was examined in a multicenter (n=22 sites) US cohort study of emergency department patients undergoing at least 1 hs-cTnT (CV Data Mart Biomarker cohort). We then determined the performance of a single hs-cTnT<6 ng/L (biomarker alone) to exclude acute myocardial injury (subsequent hs-cTnT >99th percentile in those with an initial hs-cTnT<6 ng/L). The clinically intended rule-out strategy combining a nonischemic ECG with a baseline hs-cTnT<6 ng/L was subsequently tested in an adjudicated cohort in which the diagnostic performance for ruling out acute myocardial infarction and safety (myocardial infarction or death at 30 days) were evaluated., Results: A total of 85 610 patients were evaluated in the CV Data Mart Biomarker cohort, among which 24 646 (29%) had a baseline hs-cTnT<6 ng/L. Women were more likely than men to have hs-cTnT<6 ng/L (38% versus 20%, P <0.0001). Among 11 962 patients with baseline hs-cTnT<6 ng/L and serial measurements, only 1.2% developed acute myocardial injury, resulting in a negative predictive value of 98.8% (95% CI, 98.6-99.0) and sensitivity of 99.6% (95% CI, 99.5-99.6). In the adjudicated cohort, a nonischemic ECG with hs-cTnT<6 ng/L identified 33% of patients (610/1849) as low risk and resulted in a negative predictive value and sensitivity of 100% and a 30-day rate of 0.2% for myocardial infarction or death., Conclusions: A single hs-cTnT below the limit of quantitation of 6 ng/L is a safe and rapid method to identify a substantial number of patients at very low risk for acute myocardial injury and infarction.

Background: Uncompensated vestibular hypofunction can result in symptoms of dizziness, imbalance, and/or oscillopsia, gaze and gait instability, and impaired navigation and spatial orientation; thus, may negatively impact an individual's quality of life, ability to perform activities of daily living, drive, and work. It is estimated that one-third of adults in the United States have vestibular dysfunction and the incidence increases with age. There is strong evidence supporting vestibular physical therapy for reducing symptoms, improving gaze and postural stability, and improving function in individuals with vestibular hypofunction. The purpose of this revised clinical practice guideline is to improve quality of care and outcomes for individuals with acute, subacute, and chronic unilateral and bilateral vestibular hypofunction by providing evidence-based recommendations regarding appropriate exercises., Methods: These guidelines are a revision of the 2016 guidelines and involved a systematic review of the literature published since 2015 through June 2020 across 6 databases. Article types included meta-analyses, systematic reviews, randomized controlled trials, cohort studies, case-control series, and case series for human subjects, published in English. Sixty-seven articles were identified as relevant to this clinical practice guideline and critically appraised for level of evidence., Results: Based on strong evidence, clinicians should offer vestibular rehabilitation to adults with unilateral and bilateral vestibular hypofunction who present with impairments, activity limitations, and participation restrictions related to the vestibular deficit. Based on strong evidence and a preponderance of harm over benefit, clinicians should not include voluntary saccadic or smooth-pursuit eye movements in isolation (ie, without head movement) to promote gaze stability. Based on moderate to strong evidence, clinicians may offer specific exercise techniques to target identified activity limitations and participation restrictions, including virtual reality or augmented sensory feedback. Based on strong evidence and in consideration of patient preference, clinicians should offer supervised vestibular rehabilitation. Based on moderate to weak evidence, clinicians may prescribe weekly clinic visits plus a home exercise program of gaze stabilization exercises consisting of a minimum of: (1) 3 times per day for a total of at least 12 minutes daily for individuals with acute/subacute unilateral vestibular hypofunction; (2) 3 to 5 times per day for a total of at least 20 minutes daily for 4 to 6 weeks for individuals with chronic unilateral vestibular hypofunction; (3) 3 to 5 times per day for a total of 20 to 40 minutes daily for approximately 5 to 7 weeks for individuals with bilateral vestibular hypofunction. Based on moderate evidence, clinicians may prescribe static and dynamic balance exercises for a minimum of 20 minutes daily for at least 4 to 6 weeks for individuals with chronic unilateral vestibular hypofunction and, based on expert opinion, for a minimum of 6 to 9 weeks for individuals with bilateral vestibular hypofunction. Based on moderate evidence, clinicians may use achievement of primary goals, resolution of symptoms, normalized balance and vestibular function, or plateau in progress as reasons for stopping therapy. Based on moderate to strong evidence, clinicians may evaluate factors, including time from onset of symptoms, comorbidities, cognitive function, and use of medication that could modify rehabilitation outcomes., Discussion: Recent evidence supports the original recommendations from the 2016 guidelines. There is strong evidence that vestibular physical therapy provides a clear and substantial benefit to individuals with unilateral and bilateral vestibular hypofunction., Limitations: The focus of the guideline was on peripheral vestibular hypofunction; thus, the recommendations of the guideline may not apply to individuals with central vestibular disorders. One criterion for study inclusion was that vestibular hypofunction was determined based on objective vestibular function tests. This guideline may not apply to individuals who report symptoms of dizziness, imbalance, and/or oscillopsia without a diagnosis of vestibular hypofunction., Disclaimer: These recommendations are intended as a guide to optimize rehabilitation outcomes for individuals undergoing vestibular physical therapy. The contents of this guideline were developed with support from the American Physical Therapy Association and the Academy of Neurologic Physical Therapy using a rigorous review process. The authors declared no conflict of interest and maintained editorial independence.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A369)., Competing Interests: All members of the Guideline Development Group and Advisory Board completed conflict of interest forms, which included information about grant funding, royalties, device/company shares, legal assistance, patents, device consultant/advocacy, publications, presentations, and clinical practice related to the Clinical Practice Guideline (CPG) topic. Forms were submitted to the Academy of Neurologic Physical Therapy (ANPT) Evidence-Based Documents Committee, who monitored and managed any identified perceived conflicts of interest. All recommendations were written as a group per standard CPG methodology. Therefore, no one individual made all the decisions. These recommendations are intended as a guide to optimize rehabilitation outcomes for individuals undergoing vestibular physical therapy. The contents of this guideline were developed with support from the American Physical Therapy Association and the Academy of Neurologic Physical Therapy using a rigorous review process. The authors declared no conflict of interest and maintained editorial independence., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Academy of Neurologic Physical Therapy, APTA.)

Objectives: Assessment of surgical outcome in acromegaly is typically recommended at 3 to 6 months following surgery. The purpose of this study was to determine if insulin-like growth factor 1 (IGF-1) concentrations at 6 weeks were equally predictive of surgical outcomes compared with IGF-1 concentrations at 3 to 6 months postoperatively applying newer IGF-1 assays., Methods: Retrospective review of patients with newly diagnosed acromegaly who had surgery between 2013 and 2020 and had postoperative IGF-1 measured by 6 weeks and 3 to 6 months., Results: At 6 weeks, 20 (35%) of the total 57 had normal IGF-1 and became abnormal in 1 at 3 to 6 months, whereas 37 (65%) of 57 had abnormal IGF-1 concentrations at 6 weeks, which normalized in 1 patient by 3 to 6 months. In patients who changed clinical status, IGF-1 at 6 weeks was within ±0.1-fold of normal. Although a difference was seen between median IGF-1 concentrations (286 vs 267 ng/mL, P = .009) at 6 weeks and 3 to 6 months, the mean reduction was small (-19.9 ng/mL)., Conclusions: Compared with 3 to 6 months, use of IGF-1 at 6 weeks was associated with a change in clinical status in 3.5% of patients. Therefore, in most patients, IGF-1 at 6 weeks can be used to assess clinical outcome via newer assays., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate inter-rater agreement for sonographic classification of stomach position (as a surrogate for liver herniation) in fetal left congenital diaphragmatic hernia (LCDH) among: (i) fetal medicine specialists from the North American Fetal Therapy Network (NAFTNet) centers within and without the fetal endoscopic tracheal occlusion (FETO) consortium and in comparison to an expert external reviewer (ER1); and (iii) among two expert ERs (ER1 and ER2)., Methods: Forty-eight physicians from 26 NAFTNet centers and 2 ERs were asked to assess 13 sonographic clips of isolated LCDH and classify stomach position as "intra-abdominal," "anterior left chest," "mid to posterior left chest," or "retro-cardiac" based on the classification published by Basta et al. 8 Interrater agreement was assessed by determining proportion of stomach position ratings concordant amongst NAFTNet participants and ER1. Agreement for stomach position between ERs was calculated using kappa statistics., Results: Agreement for stomach position was 69% (39%-85%; n = 19) and 54% (23%-92%; n = 29) among FETO and non-FETO NAFTNet participants, respectively, when compared to ER1. Most disagreement in stomach position was related to a discrepancy of one position. ERs were in agreement for stomach position in 5 of 13 cases (38.5%) and inter-rater agreement was highest for "anterior" stomach position., Conclusion: Interrater agreement for stomach position assessment in CDH was poor across NAFTNet and indeed amongst expert reviewers., (© 2021 John Wiley & Sons Ltd.)

The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein syntaxin-5 (Stx5) is essential for Golgi transport. In humans, the STX5 mRNA encodes two protein isoforms, Stx5 Long (Stx5L) from the first starting methionine and Stx5 Short (Stx5S) from an alternative starting methionine at position 55. In this study, we identify a human disorder caused by a single missense substitution in the second starting methionine (p.M55V), resulting in complete loss of the short isoform. Patients suffer from an early fatal multisystem disease, including severe liver disease, skeletal abnormalities and abnormal glycosylation. Primary human dermal fibroblasts isolated from these patients show defective glycosylation, altered Golgi morphology as measured by electron microscopy, mislocalization of glycosyltransferases, and compromised ER-Golgi trafficking. Measurements of cognate binding SNAREs, based on biotin-synchronizable forms of Stx5 (the RUSH system) and Förster resonance energy transfer (FRET), revealed that the short isoform of Stx5 is essential for intra-Golgi transport. Alternative starting codons of Stx5 are thus linked to human disease, demonstrating that the site of translation initiation is an important new layer of regulating protein trafficking., (© 2021. The Author(s).)

Background and Aims: The case-mix of patients with intestinal failure due to short bowel syndrome (SBS-IF) can differ among centres and may also be affected by the timeframe of data collection. Therefore, the ESPEN international multicenter cross-sectional survey was analyzed to compare the characteristics of SBS-IF cohorts collected within the same timeframe in different countries., Methods: The study included 1880 adult SBS-IF patients collected in 2015 by 65 centres from 22 countries. The demographic, nutritional, SBS type (end jejunostomy, SBS-J; jejuno-colic anastomosis, SBS-JC; jejunoileal anastomosis with an intact colon and ileocecal valve, SBS-JIC), underlying disease and intravenous supplementation (IVS) characteristics were analyzed. IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorized as <1, 1-2, 2-3 and >3 L/day., Results: In the entire group: 60.7% were females and SBS-J comprised 60% of cases, while mesenteric ischaemia (MI) and Crohn' disease (CD) were the main underlying diseases. IVS dependency was longer than 3 years in around 50% of cases; IVS was infused ≥5 days/week in 75% and FE in 10% of cases. Within the SBS-IF cohort: CD was twice and thrice more frequent in SBS-J than SBS-JC and SBS-JIC, respectively, while MI was more frequent in SBS-JC and SBS-JIC. Within countries: SBS-J represented 75% or more of patients in UK and Denmark and 50-60% in the other countries, except Poland where SBS-JC prevailed. CD was the main underlying disease in UK, USA, Denmark and The Netherlands, while MI prevailed in France, Italy and Poland., Conclusions: SBS-IF type is primarily determined by the underlying disease, with significant variation between countries. These novel data will be useful for planning and managing both clinical activity and research studies on SBS., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background Anxiety disorders are the most prevalent mental disorders and are an emerging risk factor for coronary artery disease and its complications. We determine the relationship between having a clinical diagnosis of an anxiety disorder and coronary endothelial dysfunction (CED) using invasive coronary reactivity testing across both sexes. Methods and Results Patients presenting with chest pain and nonobstructive coronary artery disease (stenosis <40%) at coronary angiography underwent an invasive assessment of CED. Patients were categorized as having a clinical diagnosis of an anxiety disorder at the time of coronary angiography by chart review. The frequency of CED was compared between patients with versus without an anxiety disorder and after stratifying patients by sex. Between 1992 and 2020, 1974 patients (mean age, 51.3 years; 66.2% women) underwent invasive coronary reactivity testing, of which 550 (27.9%) had a documented anxiety disorder at the time of angiography. There was a significantly higher proportion of patients with any type of CED in those with an anxiety disorder in all patients (343 [62.7%] versus 790 [56.4%]; P =0.011) that persisted in women but not in men. After adjusting for covariables, anxiety was significantly associated with any CED among all patients (odds ratio [95% CI], 1.36 [1.10-1.68]; P =0.004), and after stratifying by sex in women but not in men. Conclusions Anxiety disorders are significantly associated with CED in women presenting with chest pain and nonobstructive coronary artery disease. Thus, CED may represent a mechanism underpinning the association between anxiety disorders and coronary artery disease and its complications, highlighting the role of anxiety as a potential therapeutic target to prevent cardiovascular events.

Background: Limited data exist on high-sensitivity cardiac troponin (hs-cTn) for risk-stratification in COVID-19., Methods: We conducted a multicenter, retrospective, observational, US-based study of COVID-19 patients undergoing hs-cTnT. Outcomes included short-term mortality (in-hospital and 30-days post-discharge) and a composite of major adverse events, including respiratory failure requiring mechanical ventilation, cardiac arrest, and shock within the index presentation and/or mortality during the index hospitalization or within 30-days post-discharge., Results: Among 367 COVID-19 patients undergoing hs-cTnT, myocardial injury was identified in 46%. They had a higher risk for mortality (20% vs 12%, P < 0.0001; unadjusted HR 4.44, 95% CI 2.13-9.25, P < 0.001) and major adverse events (35% vs. 11%, P < 0.0001; unadjusted OR 4.29, 95% CI 2.50-7.40, P < 0.0001). Myocardial injury was associated with major adverse events (adjusted OR 3.84, 95% CI 2.00-7.36, P < 0.0001) but not mortality. Baseline (adjusted OR 1.003, 95% CI 1.00-1.007, P = 0.047) and maximum (adjusted OR 1.005, 95% CI 1.001-1.009, P = 0.0012) hs-cTnT were independent predictors of major adverse events. Most (95%) increases were due to myocardial injury, with 5% (n = 8) classified as type 1 or 2 myocardial infarction. A single hs-cTnT <6 ng/L identified 26% of patients without mortality, with a 94.9% (95% CI 87.5-98.6) negative predictive value and 93.1% sensitivity (95% CI 83.3-98.1) for major adverse events in those presenting to the ED., Conclusions: Myocardial injury is frequent and prognostic in COVID-19. While most hs-cTnT increases are modest and due to myocardial injury, they have important prognostic implications. A single hs-cTnT <6 ng/L at presentation may facilitate the identification of patients with a favorable prognosis., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Limited U.S. data exist regarding high-sensitivity cardiac troponin (cTn) implementation., Objectives: This study sought to evaluate the impact of high-sensitivity cardiac troponin T (cTnT) implementation., Methods: Observational U.S. cohort study of emergency department (ED) patients undergoing measurement of cTnT during the transition from 4th (pre-implementation March 12, 2018, to September 11, 2018) to 5th generation (Gen) cTnT (post-implementation September 12, 2018, to March 11, 2019). Diagnoses were adjudicated following the Fourth Universal Definition of Myocardial Infarction (MI). Resources evaluated included length of stay, hospitalizations, and cardiac testing., Results: In this study, 3,536 unique patients were evaluated, including 2,069 and 2,491 ED encounters pre- and post-implementation. Compared with 4th Gen cTnT, encounters with ≥1 cTnT >99th percentile increased using 5th Gen cTnT (15% vs. 47%; p < 0.0001). Acute MI (3.3% vs. 8.1%; p < 0.0001) and myocardial injury (11% vs. 38%; p < 0.0001) increased. Although type 1 MIs increased (1.7% vs. 2.9%; p = 0.0097), the overall MI increase was largely due to more type 2 MIs (1.6% vs. 5.2%; p < 0.0001). Women were less likely than men to have MI using 4th Gen cTnT (2.3% vs. 4.4%; p = 0.008) but not 5th Gen cTnT (7.7% vs. 8.5%; p = 0.46). Overall length of stay and stress testing were reduced, and angiography was increased (all p < 0.05). Among those without cTnT increases, there were more ED discharges and a reduction in length of stay, echocardiography, and stress tests (all p < 0.05)., Conclusions: High-sensitivity cTnT implementation resulted in a marked increase in myocardial injury and MI, particularly in women and patients with type 2 MI. Despite this, except for angiography, overall resource use did not increase. Among those without cTnT increases, there were more ED discharges and fewer cardiac tests., Competing Interests: Funding Support and Author Disclosures This publication was made possible in part by the Mayo Clinic CTSA through grant UL1TR002377 from the National Center for Advancing Translational Sciences, a component of the National Institutes of Health. Dr. Jaffe has consulted or presently consults for most of the major diagnostics companies, including Beckman, Abbott, Siemens, ET Healthcare, Roche, Radiometer, Sphingotec, Amgen, and Novartis. Dr. Sandoval has previously served on the Advisory Boards for Roche Diagnostics and Abbott Diagnostics without personal compensation; and has also been a speaker without personal financial compensation for Abbott Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the association of voice analysis with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Patients and Methods: A vocal biomarker, a unitless scalar with a value between 0 and 1, was developed based on 434 voice samples. The biomarker training was followed by a prospective, multicenter, observational study. All subjects were tested for SARS-CoV-2, had their voice recorded to a smartphone application, and gave their informed consent to participate in the study. The association of SARS-CoV-2 infection with the vocal biomarker was evaluated., Results: The final study population included 80 subjects with a median age of 29 [range, 23 to 36] years, of whom 68% were men. Forty patients were positive for SARS-CoV-2. Infected patients were 12 times more likely to report at least one symptom (odds ratio, 11.8; P <.001). The vocal biomarker was significantly higher among infected patients (OR, 0.11; 95% CI, 0.06 to 0.17 vs OR, 0.19; 95% CI, 0.12 to 0.3; P =.001). The area under the receiver operating characteristic curve evaluating the association of the vocal biomarker with SARS-CoV-2 status was 72%. With a biomarker threshold of 0.115, the results translated to a sensitivity and specificity of 85% (95% CI, 70% to 94%) and 53% (95% CI, 36% to 69%), respectively. When added to a self-reported symptom classifier, the area under the curve significantly improved from 0.775 to 0.85., Conclusion: Voice analysis is associated with SARS-CoV-2 status and holds the potential to improve the accuracy of self-reported symptom-based screening tools. This pilot study suggests a possible role for vocal biomarkers in screening for SARS-CoV-2-infected subjects., (© 2021 The Authors.)

Background: Adoption of the Digital Imaging and Communications in Medicine (DICOM) standard for whole slide images (WSIs) has been slow, despite significant time and effort by standards curators. One reason for the lack of adoption is that there are few tools which exist that can meet the requirements of WSIs, given an evolving ecosystem of best practices for implementation. Eventually, vendors will conform to the specification to ensure enterprise interoperability, but what about archived slides? Millions of slides have been scanned in various proprietary formats, many with examples of rare histologies. Our hypothesis is that if users and developers had access to easy to use tools for migrating proprietary formats to the open DICOM standard, then more tools would be developed as DICOM first implementations., Methods: The technology we present here is dicom&#95;wsi, a Python based toolkit for converting any slide capable of being read by the OpenSlide library into DICOM conformant and validated implementations. Moreover, additional postprocessing such as background removal, digital transformations (e.g., ink removal), and annotation storage are also described. dicom&#95;wsi is a free and open source implementation that anyone can use or modify to meet their specific purposes., Results: We compare the output of dicom&#95;wsi to two other existing implementations of WSI to DICOM converters and also validate the images using DICOM capable image viewers., Conclusion: dicom&#95;wsi represents the first step in a long process of DICOM adoption for WSI. It is the first open source implementation released in the developer friendly Python programming language and can be freely downloaded at ., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Pathology Informatics.)

Purpose: The safety of the team anesthesia model routinely used by the specialty of oral and maxillofacial surgery has recently been called into question. The purpose of this article is to measure the frequency of adverse anesthetic events related to ambulatory surgical procedures performed under intravenous (IV) sedation by the Division of Oral and Maxillofacial Surgery at the Mayo Clinic during a 15-year period using the team anesthesia model., Materials and Methods: A retrospective cohort study was designed, and a sample of subjects identified undergoing IV sedation at Mayo Clinic from 2004 to 2019. The primary outcome variable of interest was the presence of anesthetic-related adverse events (AEs) consistent with the World Society of Intravenous Anesthesia International Sedation Task Force's intervention-based definitions of adverse anesthetic events. Additional covariates included patient age, gender, American Society of Anesthesiologists (ASA) score, type of surgical procedure performed, and the type/dosage of medications administered periprocedurally. Univariate logistic regression analysis was used to assess for associations between AEs and covariates., Results: The study identified 17,634 sedations administered to 16,609 unique subjects. In 17,634 sedations, 16 (0.1%) AEs and no subject deaths (0%) were identified. There were no statistically significant associations between AEs and age (hazard ratio [HR], 0.4; 95% confidence interval [95% CI], 0.2 to 1.3; P = .13); gender (HR, 0.9; 95% CI, 0.3 to 2.5; P = .87); ASA 2 classification (HR, 1.6; 95% CI, 0.6 to 4.5; P = .33); ASA 3 classification (HR, 1.3; 95% CI, 0.1 to 22.0; P = .86), or types of IV sedation medications administered during the procedure: fentanyl (HR, 0.4; 95% CI, 0.02 to 6.3; P = .5); midazolam (HR, 1.0; 95% CI, 0.2 to 4.3; P = .98); propofol (HR, 1.0; 95% CI, 0.3 to 3.5; P = .99); or ketamine (HR, 1.0; 95% CI, 0.1 to 7.3; P = .97)., Conclusions: The frequency of AEs (0.1%) and 0% mortality rate reported in this study demonstrate that the anesthesia team model used by oral and maxillofacial surgeons compares favorably to standardized intervention-based adverse anesthetic event outcomes reported by other nonanesthesiology specialties routinely performing outpatient procedural sedation., (Copyright © 2020 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Clinical decision-making that best serves the interests of our patients requires the synthesis of evidence-based medicine, sound clinical judgment and guidelines. However, a relatively low percentage of clinical guidelines are based on well-designed prospective randomized clinical trials. Thus the foundation on which good clinical outcomes can be reasonably expected should be based on i) data derived from the most applicable and highest quality clinical studies available, and ii) 'tried and tested' clinical maxims acquired through experience that are, in turn, those ideas that are in keeping with a reasonable body of medical opinion. It follows that poor decision-making and unfavorable clinical outcomes can be linked to inappropriate or inferior quality evidence, or incorrectly conceived or implemented clinical judgment. Here we review selected areas of recent controversy in clinical cardiology, highlighting the critical role of evidence-based medicine when making informed clinical decisions to help avoid harm in our patients., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest or competing interests to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Aims: Vacuolar H+-ATP complex (V-ATPase) is a multisubunit protein complex required for acidification of intracellular compartments. At least five different factors are known to be essential for its assembly in the endoplasmic reticulum (ER). Genetic defects in four of these V-ATPase assembly factors show overlapping clinical features, including steatotic liver disease and mild hypercholesterolemia. An exception is the assembly factor vacuolar ATPase assembly integral membrane protein (VMA21), whose X-linked mutations lead to autophagic myopathy., Approach and Results: Here, we report pathogenic variants in VMA21 in male patients with abnormal protein glycosylation that result in mild cholestasis, chronic elevation of aminotransferases, elevation of (low-density lipoprotein) cholesterol and steatosis in hepatocytes. We also show that the VMA21 variants lead to V-ATPase misassembly and dysfunction. As a consequence, lysosomal acidification and degradation of phagocytosed materials are impaired, causing lipid droplet (LD) accumulation in autolysosomes. Moreover, VMA21 deficiency triggers ER stress and sequestration of unesterified cholesterol in lysosomes, thereby activating the sterol response element-binding protein-mediated cholesterol synthesis pathways., Conclusions: Together, our data suggest that impaired lipophagy, ER stress, and increased cholesterol synthesis lead to LD accumulation and hepatic steatosis. V-ATPase assembly defects are thus a form of hereditary liver disease with implications for the pathogenesis of nonalcoholic fatty liver disease., (© 2020 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)