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Background: Whether systemic oxygen levels (SaO 2 ) during exercise can provide a window into invasively derived exercise hemodynamic profiles in patients with undifferentiated dyspnea on exertion is unknown., Methods: We performed cardiopulmonary exercise testing with invasive hemodynamic monitoring and arterial blood gas sampling in individuals referred for dyspnea on exertion. Receiver operator analysis was performed to distinguish heart failure with preserved ejection fraction from pulmonary arterial hypertension., Results: Among 253 patients (mean ± SD, age 63 ± 14 years, 55% female, arterial O 2 [PaO 2 ] 87 ± 14 mmHg, SaO 2 96% ± 4%, resting pulmonary capillary wedge pressure [PCWP] 18 ± 4mmHg, and pulmonary vascular resistance [PVR] 2.7 ± 1.2 Wood units), there was no exercise PCWP threshold, measured up to 49 mmHg, above which hypoxemia was consistently observed. Exercise PaO 2 was not correlated with exercise PCWP (rho = 0.04; P = 0.51) but did relate to exercise PVR (rho = -0.46; P < 0.001). Exercise PaO 2 and SaO 2 levels distinguished left-heart-predominant dysfunction from pulmonary-vascular-predominant dysfunction with an area under the curve of 0.89 and 0.89, respectively., Conclusion: Systemic O 2 levels during exercise distinguish relative pre- and post-capillary pulmonary hemodynamic abnormalities in patients with undifferentiated dyspnea. Hypoxemia during upright exercise should not be attributed to isolated elevation in left heart filling pressures and should prompt consideration of pulmonary vascular dysfunction., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Disorganized speech is a key component of formal thought disorder (FTD) in schizophrenia. Recent work has tied disorganized speech to deficits in metacognition, or one's ability to integrate experiences to form complex mental representations. The level of FTD at which differences in metacognitive capacity emerge remains unclear. Across two studies, using different cut scores to form FTD groups, we aimed to 1) explore the relationship between disorganized speech and metacognition and 2) compare trained rater and automated analysis methods. Clinical interviews were coded for disorganized speech and metacognition using the Communication Disturbances Index (CDI), Coh-Metrix multidimensional indices, and Metacognition Assessment Scale. In Study 1, we examined CDI and Coh-Metrix's ability to predict metacognition in FTD (n = 16) and non-FTD (n = 29) groups. We hypothesized the FTD group would have lower metacognition and that both CDI and Coh-Metrix would account for significant variance in metacognition. In Study 2, we conducted the same analyses with an independent sample using more stringent FTD cut scores (FTD: n = 23; non-FTD: n = 23). Analyses indicated that at a moderate but not mild cutoff: 1) automated methods differentiated FTD and non-FTD groups, 2) differences in metacognition emerged, and 3) behavioral measures accounted for significant variance (34%) in metacognition. Results emphasize the importance of setting the FTD cutoff at a moderate level and using samples that contain high levels of FTD. Findings extend research linking FTD and metacognition and demonstrate the benefit of pairing trained rater and automated speech measures., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In recent decades, the scientific community has seen an increased interest in rigor and reproducibility. In 2017, concerns about methodological thoroughness and reporting practices were implicated as significant barriers to reproducibility within the preclinical cardiovascular literature, particularly in studies using animal research. The Langendorff, whole heart technique has proven to be an invaluable research tool, being modified in a myriad of ways to probe questions across the spectrum of physiological and pathophysiological functions of the heart. As a result, significant variability in the application of the Langendorff technique exists. This literature review quantifies the different methods employed in the implementation of the Langendorff technique and provides brief examples of how individual parametric differences can impact the outcomes and interpretation of studies. From 2017 to 2020, significant variability of animal models, anesthesia, cannulation time, perfusate composition, pH, and temperature demonstrate that the technique has diversified to meet new challenges and answer different scientific questions. The review also reveals which individual methods are most frequently reported, even if there is no explicit agreement upon which parameters should be reported. The analysis of methods related to the Langendorff technique suggests a framework for considering methodological approach when interpreting seemingly contradictory results, rather than concluding that results are irreproducible.

Objectives: This study aimed to evaluate hemodynamic correlates of inducible blood pressure (BP) pulsatility with exercise in heart failure with preserved ejection fraction (HFpEF), to identify relationships to outcomes, and to compare this with heart failure with reduced ejection fraction (HFrEF)., Background: In HFpEF, determinants and consequences of exercise BP pulsatility are not well understood., Methods: We measured exercise BP in 146 patients with HFpEF who underwent invasive cardiopulmonary exercise testing. Pulsatile BP was evaluated as proportionate pulse pressure (PrPP), the ratio of pulse pressure to systolic pressure. We measured pulmonary arterial catheter pressures, Fick cardiac output, respiratory gas exchange, and arterial stiffness. We correlated BP changes to central hemodynamics and cardiovascular outcome (nonelective cardiovascular hospitalization) and compared findings with 57 patients with HFrEF from the same referral population., Results: In HFpEF, only age (standardized beta = 0.593; P < 0.001), exercise stroke volume (standardized beta = 0.349; P < 0.001), and baseline arterial stiffness (standardized beta = 0.182; P = 0.02) were significant predictors of peak exercise PrPP in multivariable analysis (R = 0.661). In HFpEF, lower PrPP was associated with lower risk of cardiovascular events, despite adjustment for confounders (HR:0.53 for PrPP below median; 95% CI: 0.28-0.98; P = 0.043). In HFrEF, lower exercise PrPP was not associated with arterial stiffness but was associated with lower peak exercise stroke volume (P = 0.013) and higher risk of adverse cardiovascular outcomes (P = 0.004)., Conclusions: In HFpEF, greater inducible BP pulsatility measured using exercise PrPP reflects greater arterial stiffness and higher risk of adverse cardiovascular outcomes, in contrast to HFrEF where inducible exercise BP pulsatility relates to stroke volume reserve and favorable outcome., Competing Interests: Funding Support and Author Disclosures Dr Namasivayam is supported by a Clinical and Research Fellowship from the Division of Cardiology, Massachusetts General Hospital, Harvard Medical School; and is a recipient of the St. Vincent’s Clinic Travelling Fellowship Award. Dr Lewis is supported by the American Heart Association Award 15GPSGC24800006 and by the National Heart, Lung and Blood Institute Awards R01-HL 131029 and R01-HL151841. Dr Nayor is supported by National Institutes of Health/National Heart, Lung, and Blood Institute K23-HL138260. Dr Ho is supported by National Institutes of Health/National Heart, Lung, and Blood Institute R01-HL134893 and R01-HL140224. Dr Malhotra is supported by Transformation Project Award 18TPA34230025 from the American Heart Association and grant R01-HL142809 from the National Heart, Lung, and Blood Institute. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Purpose The study purpose was to capture the clinical practice patterns of speech-language pathologists (SLPs) treating mild traumatic brain injury (mTBI; concussion). Study aims were to (a) characterize expert SLP practice patterns for the management of mTBI and (b) use qualitative content analysis to explore areas of quantitative variability within participants' responses. Method Using a modified Delphi approach, SLPs completed an online survey, with Round 1 responses shaping questions for Round 2. Round 2 results were analyzed using a concurrent partially mixed-methods approach with quantitative and qualitative items. Quantitative consensus agreement levels were set prestudy at 75% agreement or higher. Topic-level items that did not reach consensus were analyzed using qualitative content analysis. Participants SLPs engaging in a specialty mTBI-SLP networking group were invited to participate. Round 1 had nine participants (United States: 4, Canada: 5). Round 2 had 18 participants (United States: 12, Canada: 6), with a mean of 15.7 years of experience in mTBI (range: 3-33) and a mean of 7.6 clients with mTBI seen weekly (range: 1-25). Results Nearly all topic-level practice items met quantitative consensus (42/45). Consensus areas included using conceptual frameworks, interprofessional teaming, assessment and intervention practices, goal setting, and outcomes. Functional, collaborative, and client-centered care anchored clinical practice. Areas lacking consensus included SLP roles in mTBI mental and somatic health symptoms, specific measurement tools, and intervention dosages. Qualitative themes that emerged included limited interprofessional awareness for the role of SLPs in mTBI and challenges in measurement selection. Conclusions Study aims were met with clear consensus on clinical patterns implemented by SLPs specializing in mTBI. Results will inform both current clinical practices and future practice guidelines. High-level guidance and advocacy are needed to clarify SLP practice concerns and advance interprofessional education. Future work should address identified gaps, including targeted assessment tools and consensus on intervention methods.

Purpose The purpose of this study was to evaluate changes in cognitive-communication performance using Woodcock-Johnson IV Tests (WJIV) from pre-injury baseline to post sport-related concussion. It was hypothesized that individual subtest performances would decrease postinjury in symptomatic individuals. Method This prospective longitudinal observational nested cohort study of collegiate athletes assessed cognitive-communicative performance at preseason baseline and postinjury. Three hundred and forty-two male and female undergraduates at high risk for sport-related concussion participated in preseason assessments, and 18 individuals met criteria post injury. WJIV subtest domains included Word Finding, Speeded Reading Comprehension, Auditory Comprehension, Verbal Working Memory, Story Retell, and Visual Processing (letter and number). The power calculation was not met, and therefore data were conservatively analyzed with descriptive statistics and a planned subgroup analysis based on symptomatology. Results Individual changes from baseline to postinjury were evaluated using differences in standard score performance. For symptomatic individuals, mean negative decreases in performance were found for Retrieval Fluency, Sentence Reading Fluency, Pattern Matchings, and all cluster scores postinjury. Individual performance declines also included decreases in story retell, verbal working memory, and visual processing. Conclusions This study identified within-subject WJIV performance decline in communication domains post sport-related concussion and reinforces that cognitive-communication dysfunction should be considered in mild traumatic brain injury. Key cognitive-communication areas included speeded naming, reading, and verbal memory, though oral comprehension was not sensitive to change. Future clinical research across diverse populations is needed to expand these preliminary findings.

Objective: Social deficits are already exhibited by people at risk for schizophrenia-spectrum disorders. Technological advances have made passive detection of social deficits possible at granular levels., Method: In this real-world study, we tested if schizotypy status (high/low) predicted two types of social behavior: (1) being around other people; and (2) actively socializing with others. We also examined if schizotypy influences relationships between social behavior and affect using subjective and objective instruments., Results: Our findings revealed that socializing with others was significantly decreased in the high schizotypy group. Positive affect increased in social situations and predicted later social behavior in those low, but not high, in schizotypy., Conclusion: Decreased social behavior in schizotypy may be explained, in part, by these individuals being less incentivized than their peers to pursue social situations. Future studies should test this explanation in larger samples exhibiting elevated positive, negative, and disorganized schizotypy traits., (© 2020 Wiley Periodicals LLC.)

Background: Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described in select individuals; however, clinical and prognostic implications of exercise pulmonary hypertension (exPH) among broader samples remains unclear., Objectives: This study sought to investigate the association of exPH with clinical determinants and outcomes., Methods: The authors studied individuals with chronic exertional dyspnea and preserved ejection fraction who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring. Exercise pulmonary hypertension was ascertained using minute-by-minute PAP and cardiac output (CO) measurements to calculate a PAP/CO slope, and exPH defined as a PAP/CO slope >3 mm Hg/l/min. The primary outcome was cardiovascular (CV) hospitalization or all-cause mortality., Results: Among 714 individuals (age 57 years, 59% women), 296 (41%) had abnormal PAP/CO slopes. Over a mean follow-up of 3.7 ± 2.9 years, there were 208 CV or death events. Individuals with abnormal PAP/CO slope had a 2-fold increased hazard of future CV or death event (multivariable-adjusted hazard ratio: 2.03; 95% confidence interval: 1.48 to 2.78; p < 0.001). The association of abnormal PAP/CO slope with outcomes remained significant after excluding rest PH (n = 146, hazard ratio: 1.75; 95% confidence interval: 1.21 to 2.54; p = 0.003). Both pre- and post-capillary contributions to exPH independently predicted adverse events (p < 0.001 for both)., Conclusions: Exercise pulmonary hypertension is independently associated with CV event-free survival among individuals undergoing evaluation of chronic dyspnea. These findings suggest incremental value of exercise hemodynamic assessment to resting measurements alone in characterizing the burden of PH in individuals with dyspnea. Whether PH and PH subtypes unmasked by exercise can be used to guide targeted therapeutic interventions requires further investigation., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Sex differences in heart failure with preserved ejection fraction (HFpEF) have been established, but insights into the mechanistic drivers of these differences are limited., Objective: To examine sex differences in cardiometabolic profiles and exercise hemodynamic profiles among individuals with HFpEF., Design, Setting, and Participants: This cross-sectional study was conducted at a single-center tertiary care referral hospital from December 2006 to June 2017 and included 295 participants who met hemodynamic criteria for HFpEF based on invasive cardiopulmonary exercise testing results. We examined sex differences in distinct components of oxygen transport and utilization during exercise using linear and logistic regression models. The data were analyzed from June 2018 to May 2019., Main Outcomes and Measures: Resting and exercise gas exchange and hemodynamic parameters obtained during cardiopulmonary exercise testing., Results: Of 295 participants, 121 (41.0%) were men (mean [SD] age, 64 [12] years) and 174 (59.0%) were women (mean [SD] age, 61 [13] years). Compared with men, women with HFpEF in this tertiary referral cohort had fewer comorbidities, including diabetes, insulin resistance, and hypertension, and a more favorable adipokine profile. Exercise capacity was similar in men and women (percent predicted peak oxygen [O2] consumption: 66% in women vs 68% in men; P = .38), but women had distinct deficits in components of the O2 pathway, including worse biventricular systolic reserve (multivariable-adjusted analyses: ΔLVEF β = -1.70; SE, 0.86; P < .05; ΔRVEF β = -2.39, SE=0.80; P = .003), diastolic reserve (PCWP/CO: β = 0.63; SE, 0.31; P = .04), and peripheral O2 extraction (C(a-v)O2 β=-0.90, SE=0.22; P < .001))., Conclusions and Relevance: Despite a lower burden of cardiometabolic disease and a similar percent predicted exercise capacity, women with HFpEF demonstrated greater cardiac and extracardiac deficits, including systolic reserve, diastolic reserve, and peripheral O2 extraction. These sex differences in cardiac and skeletal muscle responses to exercise may illuminate the pathophysiology underlying the development of HFpEF and should be investigated further.

Background: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is currently no consensus on how to define HFpEF according to various society and clinical trial criteria. How clinical and hemodynamic profiles of patients vary across definitions is unclear. We sought to determine clinical characteristics, as well as physiologic and prognostic implications of applying various criteria to define HFpEF., Methods: We examined consecutive patients with chronic exertional dyspnea (New York Heart Association class II to IV) and ejection fraction ≥50% referred for comprehensive cardiopulmonary exercise testing with invasive hemodynamic monitoring. We applied societal and clinical trial HFpEF definitions and compared clinical profiles, exercise responses, and cardiovascular outcomes., Results: Of 461 patients (age 58±15 years, 62% women), 416 met American College of Cardiology/American Heart Association (ACC/AHA), 205 met European Society of Cardiology (ESC), and 55 met Heart Failure Society of America (HFSA) criteria for HFpEF. Clinical profiles and exercise capacity varied across definitions, with peak oxygen uptake of 16.2±5.2 (ACC/AHA), 14.1±4.2 (ESC), and 12.7±3.1 mL·kg -1 ·min -1 (HFSA). A total of 243 patients had hemodynamic evidence of HFpEF (abnormal rest or exercise filling pressures), of whom 222 met ACC/AHA, 161 met ESC, and 41 met HFSA criteria. Over a mean follow-up of 3.8 years, the incidence of cardiovascular outcomes ranged from 75 (ACC/AHA) to 298 events per 1000 person-years (HFSA). Application of clinical trial definitions of HFpEF similarly resulted in distinct patient classification and prognostication., Conclusions: Use of different HFpEF classifications variably enriches for future cardiovascular events, but at the expense of not including up to 85% of individuals with physiologic evidence of HFpEF. Comprehensive phenotyping of patients with suspected heart failure highlights the limitations and heterogeneity of current HFpEF definitions and may help to refine HFpEF subgrouping to test therapeutic interventions.

Diminished productivity and elevated disorganization have been detected in the speech of individuals with schizotypy. However, the underlying mechanisms for these disruptions are not well understood. Separate lines of research suggest potential contributions from cognitive and affective systems. In this study, disorganized speech and speech production were examined in speech samples generated by schizotypy (n = 47) and non-schizotypy (n = 51) groups by assessing "reactivity" (i.e., a change in experimental compared with baseline conditions) across baseline, affective, and dual-task (i.e., cognitive) conditions. Relationships with social functioning were also examined within each group. Three key findings emerged: 1) compared to the non-schizotypy group, those with schizotypy exhibited diminished speech production in the affective condition and affective reactivity was observed; 2) the schizotypy group displayed greater levels of disorganized speech in dual-task conditions and cognitive reactivity was observed; and 3) affective reactivity for disorganized speech was linked to worse social functioning within the schizotypy group. This study provides evidence that cognitive and affective systems are uniquely involved in separate characteristics of speech in schizotypy. At this stage, cognitive systems appear to have a specific role in the organization of speech, whereas affective systems are more heavily involved in speech production. Regarding the association between affective reactivity and social functioning, previous research has demonstrated individuals highly reactive to emotional stimuli carry additional risk for conversion to psychosis. Future research identifying a subset with schizotypy who demonstrate affective reactivity could lead to a better understanding of links between schizotypy and future psychosis symptoms., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The Marcus Institute for Brain Health (MIBH) provides interdisciplinary care for adults struggling with persistent effects of mild traumatic brain injury and accompanying changes in behavioral health, with specific emphases on Veterans and retired elite athletes. The cognitive, physical, and behavioral symptoms associated with mild traumatic brain injury are interrelated, with neurobiopsychosocial modeling encompassing the factors related to recovery from a traumatic brain injury. The diffuse impacts of chronic concussive injuries require multiple clinical providers to address the breadth of symptoms, facilitating both interdisciplinary and transdisciplinary care models. By implementing integrated practice units, patients receive advanced medical care, imaging, speech-language pathology, physical therapy, behavioral health, neuropsychology, and clinical pharmacy for a cohesive diagnostic and intervention plan. Nationally, speech-language pathologists report challenges with best-practice options for concussion, particularly in the domain of assessment practices. At the MIBH, speech-language pathologists begin their assessment with a structured clinical interview that focuses on patients' needs and concerns. Evaluation modalities focus on hearing, communication, and functional cognition to guide therapeutic treatment planning. The intensive outpatient care program at MIBH incorporates both individual sessions targeting patient-centered goals and group care, where speech-language pathologists work transdisciplinarily to generalize care from all disciplines out into the community. Care practices for concussive injuries continue to evolve rapidly; speech-language pathology at the MIBH offers one such vision for excellence in clinical care., Competing Interests: Kathryn Hardin—Financial: Kathryn Hardin is a faculty member at the University of Colorado School of Medicine and receives accompanying salary support. Nonfinancial: Kathryn Hardin has reviewed works for ASHA focused on traumatic brain injury.James Kelly—Financial: Principal/sole proprietor, Kelly Neuroscience Consulting, LLC. Principal/proprietor, KLNP, LLC. Principal/proprietor, Valor Industries, LLC. Medical Advisory Board Member, Prevacus, Inc. Nonfinancial: Fellow, George W. Bush Institute Military Service Initiative., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Single measurements of left ventricular filling pressure at rest lack sensitivity for identifying heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea on exertion. We hypothesized that exercise hemodynamic measurements (ie, changes in pulmonary capillary wedge pressure [PCWP] indexed to cardiac output [CO]) may more sensitively differentiate HFpEF and non-HFpEF disease states, reflect aerobic capacity, and forecast heart failure outcomes in individuals with normal PCWP at rest., Methods and Results: We studied 175 patients referred for cardiopulmonary exercise testing with hemodynamic monitoring: controls (n=33), HFpEF with resting PCWP≥15 mm Hg (n=32), and patients with dyspnea on exertion with normal resting PCWP and left ventricular ejection fraction (DOE-nlrW; n=110). Across 1835 paired PCWP-CO measurements throughout exercise, we used regression techniques to define normative bounds of "PCWP/CO slope" in controls and tested the association of PCWP/CO slope with exercise capacity and composite cardiac outcomes (defined as cardiac death, incident resting PCWP elevation, or heart failure hospitalization) in the DOE-nlrW group. Relative to controls (PCWP/CO slope, 1.2±0.4 mm Hg/L/min), patients with HFpEF had a PCWP/CO slope of 3.4±1.9 mm Hg/L/min. We used a threshold (2 SD above the mean in controls) of 2 mm Hg/L/min to define abnormal. PCWP/CO slope >2 in DOE-nlrW patients was common (n=45/110) and was associated with reduced peak Vo 2 ( P <0.001) and adverse cardiac outcomes after adjustment for age, sex, and body mass index (hazard ratio, 3.47; P =0.03) at a median 5.3-year follow-up., Conclusions: Elevated PCWP/CO slope during exercise (>2 mm Hg/L/min) is common in DOE-nlrW and predicts exercise capacity and heart failure outcomes. These findings suggest that current definitions of HFpEF based on single measures during rest are insufficient and that assessment of exercise PCWP/CO slope may refine early HFpEF diagnosis., (© 2018 American Heart Association, Inc.)