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ABSTRACT Background The optimal exercise regimen for alleviating sarcopenia remains uncertain. This study aimed to investigate the efficacy of high‐intensity interval training (HIIT) over moderate‐intensity continuous training (MICT) in ameliorating sarcopenia. Methods We conducted a randomized crossover trial to evaluate plasma proteomic reactions to acute HIIT (four 4‐min high‐intensity intervals at 70% maximal capacity alternating with 4 min at 30%) versus MICT (constant 50% maximal capacity) in inactive adults. We explored the relationship between a HIIT‐specific protein relative to MICT, identified via comparative proteomic analysis, eukaryotic translation elongation factor 1 epsilon 1 (EEF1E1) and sarcopenia in a paired case–control study of elderly individuals (aged over 65). Young (3 months old) and aged (20 months old) mice were randomized to sedentary, HIIT and MICT groups (five sessions/week for 4 weeks; n = 8 for each group). Measurements included skeletal muscle index, hand grip strength, expression of atrophic markers Atrogin1 and MuRF1 and differentiation markers MyoD, myogenin and MyHC‐II via western blotting. We examined the impact of EEF1E1 siRNA and recombinant protein on D‐galactose‐induced myoblast senescence, measuring senescence‐associated β‐galactosidase and markers like p21 and p53. Results The crossover trial, including 10 sedentary adults (32 years old, IQR 31–32) demonstrated significant alterations in the abundance of 21 plasma proteins after HIIT compared with MICT. In the paired case–control study of 84 older adults (84 years old, IQR 69–81; 52% female), EEF1E1 was significantly increased in those with sarcopenia compared to those without (14.68 [95%CI, 2.02–27.34] pg/mL, p = 0.03) and was associated with skeletal muscle index (R2 = 0.51, p

Objective: To determine whether the number of cardiac rehabilitation (CR) sessions attended and selected clinical characteristics were predictive of patients who exhibited improvement in peak oxygen uptake (VO2peak) after CR. Patients and Methods: Using the Rochester Epidemiology Project records-linkage system, we identified all consecutive patients aged 18 years or older from Olmsted County, Minnesota, who underwent cardiopulmonary exercise testing before and after CR from 1999 to 2017. Regression models were created to assess the clinical predictors of VO2peak improvement (>0% baseline) after CR. Results: The analysis included 671 patients, of which 524 (78%) patients exhibited VO2peak improvement after CR. The significant univariate predictors of VO2peak improvement included younger age (odds ratio [OR], 0.98; 95% CI, 0.96-0.99), lower pre-CR VO2peak (OR, 0.96; 95% CI, 0.94-0.99), and no history of peripheral artery disease (OR, 0.50; 95% CI, 0.31-0.81) (all, P

Abstract Aims Baduanjin (eight silken movements), a traditional Chinese exercise, is an alternative to the most common cardiac rehabilitation programmes due to their scarcity and unaffordability in China. The aim of this study was to measure the intensity and energy expenditure during Baduanjin and to determine the relative oxygen consumption (VO2) and heart rate (HR) responses of Baduanjin compared with maximal capacity in patients with chronic heart failure. Methods and results Twenty participants (age: 65 ± 10 years, male: n = 17) with New York Heart Association II–III volunteered for this study. Participants were examined during two separate sessions, with 1–2 weeks between sessions. During session one, a symptom‐limited cardiopulmonary exercise testing was performed on a cycle ergometer for measurement of maximal exercise capacity. Additionally, participants were taught Baduanjin exercise from a professional coach and were required to do it at home until the second session when their technique was confirmed by the coach. During session two, participants performed one 9 min round of Baduanjin with continuous measurement of VO2 and HR. Measurements obtained during the Baduanjin were compared with data obtained during cardiopulmonary exercise testing. While performing Baduanjin, the mean VO2 and HR were 7.1 ± 1.2 mL/kg/min and 86.1 ± 15.2 b.p.m., respectively. Compared with the cardiopulmonary exercise test, the VO2 was 44% of their VO2max and 67% of their HRmax, categorizing Baduanjin as a moderate‐intensity exercise. The average energy expenditure during Baduanjin was 23.3 ± 4.4 kcal. Additionally, the VO2 and HR responses during Baduanjin both exhibited a bimodal pattern. Conclusions The results suggest that Baduanjin is a moderate‐intensity aerobic exercise that could be an effective and safe exercise modality for home‐based cardiac rehabilitation.

Objective: To investigate the effect of replacing sitting with standing on cardiovascular risk factors tested in clinical trials. Methods: We searched databases from inception up to August 28, 2019, for studies examining the effect of replacing sitting with standing on fasting blood glucose, fasting insulin, and lipid levels; blood pressure; body fat mass; weight; and waist circumference in healthy adults. Differences in mean ± SD values were used for pooling the data and calculating the mean differences and CIs. Results: The search found 3507 abstracts. Nine clinical trials (8 randomized and 1 nonrandomized) with 877 (64.4% [n=565] women) participants met all inclusion criteria. The mean ± SD age was 45.34±5.41 years; mean follow-up was 3.81 months, and mean difference in standing time between the intervention and control groups was 1.33 hours per day. The follow-up fasting blood glucose and body fat mass values were slightly but significantly lower than baseline records in the intervention groups compared with control groups (−2.53; 95% CI, −4.27 to −0.79 mg/dL; and −0.75; 95% CI, −0.91 to −0.59 kg). The analysis for fasting insulin levels, lipid levels, blood pressure, weight, and waist circumference revealed no significant differences. Conclusion: Replacing sitting with standing can result in very small but statistically significant decreases in fasting blood glucose levels and body fat mass with no significant effect on lipid levels, blood pressure, weight, and waist circumference. Replacing sitting with standing can be used as an adjunctive intervention to decrease the burden of cardiovascular risk factors but cannot be used as an alternative to physical activity to decrease sedentary time.

Abstract Large granular lymphocyte (LGL) leukemia is a rare hematological disorder with expansion of the T‐cell or natural killer (NK) cell lineage. Signal transducer and activator of transcription 3 (STAT3) exhibits somatic activating mutations in 30%‐40% of LGL leukemia cases. Transcriptional targets of STAT3 include inflammatory cytokines, thus previous studies have measured cytokine levels of LGL leukemia patients compared to normal donors. Sphingolipid metabolism is a growing area of cancer research, with efforts focused on drug discovery. To date, no studies have examined serum sphingolipids in LGL leukemia patients, and only one study compared a subset of cytokines between the T‐LGL and NK‐LGL subtypes. Therefore, here, we included both LGL leukemia subtypes with the goals of (a) measuring serum sphingolipids for the first time, (b) measuring cytokines to find distinctions between the subtypes, and (c) establishing relationships with STAT3 mutations and clinical data. The serum analyses identified cytokines (EGF, IP‐10, G‐CSF) and sphingolipids (SMC22, SMC24, SMC20, LysoSM) significantly different in the LGL leukemia group compared to normal donors. In a mixed STAT3 mutation group, D661Y samples exhibited the highest mean corpuscular volume (MCV) values. We explored this further by expanding the cohort to include larger groups of single STAT3 mutations. Male D661Y STAT3 samples had lower Hgb and higher MCV compared to wild type (WT) or Y640F counterparts. This is the first report examining large groups of individual STAT3 mutations. Overall, our results revealed novel serum biomarkers and evidence that D661Y mutation may show different clinical manifestation compared to WT or Y640F STAT3.

ObjectiveWe investigated age-related differences for peak oxygen uptake (peak VO2) improvement with exercise training during cardiac rehabilitation (CR).Patients and MethodsThis was a retrospective cohort study of the Mayo Clinic Rochester CR program including adult patients who attended CR (≥1 session) for any eligible indication between 1999 and 2017 and who had a cardiopulmonary exercise test pre and post CR with VO2 data (peak respiratory exchange ratio ≥1.0). Younger (20–49 yrs), midlife (50–64 yrs), and older adults (≥65 yrs) were compared using ANOVA for delta and percent change in peak VO2; and percentage of peak VO2 responders (>0% change).Results708 patients (age: 60.8 ± 12.1 years; 24% female) met inclusion criteria. Delta and percent change in peak VO2 was lower for older adults (1.6 ± 3.2 mL.kg.min−1; 12 ± 27%) compared with younger (3.7 ± 4.0 mL.kg.min−1, p < 0.001; 23 ± 28%, p = 0.002) and midlife adults (2.8 ± 3.8 mL.kg.min−1, p < 0.001; 17 ± 28%, p = 0.04). For midlife, delta change, but not percent change in peak VO2 was significantly lower (p = 0.02) compared with younger. Percentage of responders was only different between older and younger (72 vs. 86%; p = 0.008). Sensitivity analyses in non-surgical patients showed similar differences for delta change, and differences in percent change remained significant between older and younger adults (10 ± 20% vs. 16 ± 18%; p = 0.04).ConclusionsIn CR patients, older adults had lower improvement in cardiorespiratory fitness than younger and midlife adults. While excluding surgical patients reduced age-related differences, older adults still had lower cardiorespiratory fitness improvement during CR. These findings may have implications for individualizing CR programming in aging populations to reduce future cardiovascular risk.

Objective: We aimed to determine the cardiorespiratory responses during, and adaptations to, high-intensity interval training (HIIT) prescribed using ratings of perceived exertion (RPE) in patients after myocardial infarction (MI) during early outpatient cardiac rehabilitation (CR).Methods: We prospectively recruited 29 MI patients after percutaneous coronary intervention who began CR within 2 weeks after hospital discharge. Eleven patients (seven men; four women; age: 61 ± 11 yrs) who completed ≥24 supervised HIIT sessions with metabolic gas exchange measured during HIIT once weekly for 8 weeks and performed pre- and post- CR cardiopulmonary exercise tests were included in the study. Each HIIT session consisted of 5–8 high-intensity intervals [HIIs, 1-min RPE 14–17 (Borg 6–20 scale)] and low-intensity intervals (LIIs, 4-min RPE < 12). Metabolic gas exchange, heart rate (HR), and blood pressure during HIIT were measured.Results: The mean oxygen uptake (V˙O2) during HIIs across 88 sessions of HIITs [91 (14)% of V˙O2peak, median (interquartile range, IQR)] was significantly higher than the lower limit of target V˙O2 zone (75% of V˙O2peak) recommended for the HII (p < 0.001). Exercise intensity during RPE-prescribed HIITs, determined as %V˙O2peak, was highly repeatable with intra-class correlations of 0.95 (95% CI 0.86– 0.99, p < 0.001). For cardiorespiratory adaptations from the first to the last session of HIIT, treadmill speed, treadmill grade, treadmill power, V˙O2HII, %V˙O2peak, and VE during HIIs were increased (all p < 0.05), while no difference was found for HR, %HRpeak and systolic blood pressure (all p > 0.05). V˙O2peak increased by an average of 9% from pre-CR to post-CR. No adverse events occurred.Conclusion: Our results demonstrate that HIIT can be effectively prescribed using RPE in MI patients during early outpatient CR. Participation in RPE-prescribed HIIT increases exercise workload and V˙O2 during exercise training without increased perception of effort or excessive increases in heart rate or blood pressure.

Objectives: This meta-analysis aims to investigate the diagnostic value of exercise stress testing (EST) for asymptomatic coronary artery disease (CAD) among patients with type 2 diabetes mellitus (T2DM) and to ascertain the influence of different variables on the sensitivity and specificity of EST.Background: Asymptomatic CAD occurs in >1 in five diabetes mellitus patients, and it is associated with an increased risk of complications. Methods for screening asymptomatic CAD in T2DM patients are still not unified.Methods: MEDLINE (via Ovid), Embase (via Ovid), Cochrane Library, SCOPUS, PubMed, Ovid, EBSCO ASP, and Web of Science were systematically searched on June 8 and 9, 2021, for diagnostic cohort and case-control studies. We included studies that used EST to screen for CAD in asymptomatic patients with T2DM, and that used coronary angiography to diagnose CAD and had reported the basic diagnostic indicators. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess study quality. The combined effect sizes were calculated by overall analysis and multiple variable effects were explored by regression analysis and subgroup analysis.Results: Nine groups of data from eight diagnostic cohort studies, totaling 515 participants, were included. Included studies showed a low risk of bias in most items, except for flow and timing. The combined sensitivity and specificity of EST for asymptomatic CAD in patients with T2DM were 55 (48 to 61%) and 66 (61 to 70%), respectively. When non-diagnostic tests were excluded, sensitivity increased to 73 (56 to 88%). The proportion receiving angiography also significantly affected sensitivity. No significant difference was found in the duration of diabetes or other additional risk factors.Conclusions: EST is a tool of moderate sensitivity and specificity to be used for the initial screening of asymptomatic CAD in T2DM. It has the advantage of being non-invasive, relatively inexpensive, easily available in most settings, and has no radiation associated with its use. Additional research with higher quality studies in which tests that are non-diagnostic are included and flow and timing is described clearly, will be important to further our understanding of EST for asymptomatic CAD detection in patients with T2DM.Systematic review registration: PROSPERO CRD42021259555.

Background: As demand for cardiopulmonary exercise test using a supine position has increased, so have the testing options. However, it remains uncertain whether the existing evaluation criteria for the upright position are suitable for the supine position. The purpose of this meta-analysis is to compare the differences in peak oxygen uptake (VO2peak) between upright and supine lower extremity bicycle exercise.Methods: We searched PubMed, Web Of Science and Embase from inception to March 27, 2021. Self-control studies comparing VO2peak between upright and supine were included. The quality of the included studies was assessed using a checklist adapted from published papers in this field. The effect of posture on VO2peak was pooled using random/fixed effects model.Results: This meta-analysis included 32 self-control studies, involving 546 participants (63% were male). 21 studies included only healthy people, 9 studies included patients with cardiopulmonary disease, and 2 studies included both the healthy and cardiopulmonary patients. In terms of study quality, most of the studies (n = 21, 66%) describe the exercise protocol, and we judged theVO2peak to be valid in 26 (81%) studies. Meta-analysis showed that the upright VO2peak exceeded the supine VO2peak [relative VO2peak: mean difference (MD) 2.63 ml/kg/min, 95% confidence interval (CI) 1.66-3.59, I2 = 56%, p < 0.05; absolute VO2peak: MD 0.18 L/min, 95% CI 0.10-0.26, I2 = 63%, p < 0.05). Moreover, subgroup analysis showed there was more pooled difference in healthy people (4.04 ml/kg/min or 0.22 L/min) than in cardiopulmonary patients (1.03 ml/kg/min or 0.12 L/min).Conclusion: VO2peak in the upright position is higher than that in supine position. However, whether this difference has clinical significance needs further verification.Systematic Review Registration: identifier, CRD42021233468.

Abstract Background To examine the effect of high-intensity interval training (HIIT) on metabolic syndrome (MetS) and body composition in cardiac rehabilitation (CR) patients with myocardial infarction (MI). Methods We retrospectively screened 174 consecutive patients with MetS enrolled in CR following MI between 2015 and 2018. We included 56 patients who completed 36 CR sessions and pre-post dual-energy X-ray absorptiometry. Of these patients, 42 engaged in HIIT and 14 in moderate-intensity continuous training (MICT). HIIT included 4–8 intervals of high-intensity (30–60 s at RPE 15–17 [Borg 6–20]) and low-intensity (1–5 min at RPE

Abstract Background Large granular lymphocyte (LGL) leukemia is an uncommon cancer characterized by sustained clonal proliferation of LGL cells. Antibodies reactive to retroviruses have been documented in the serum of patients with LGL leukemia. Culture or molecular approaches have to date not been successful in identifying a retrovirus. Methods Because a retrovirus must integrate into the genome of an infected cell, we focused our efforts on detecting a novel retrovirus integration site in the clonally expanded LGL cells. We present a new computational tool that uses long-insert mate pair sequence data to search the genome of LGL leukemia cells for retrovirus integration sites. We also utilize recently published methods to interrogate the status of polymorphic human endogenous retrovirus type K (HERV-K) provirus in patient genomes. Results Our data show that there are no new retrovirus insertions in LGL genomes of LGL leukemia patients. However, our insertion call tool did detect four HERV-K provirus integration sites that are polymorphic in the human population but absent from the human reference genome, hg19. To determine if the prevalence of these or other polymorphic proviral HERV-Ks differed between LGL leukemia patients and the general population, we used a recently developed tool that reports sites in the human genome occupied by a known proviral HERV-K. We report that there are significant differences in the number of polymorphic HERV-Ks in the genomes of LGL leukemia patients of European origin compared to individuals with European ancestry in the 1000 genomes (KGP) data. Conclusions Our study confirms that the clonal expansion of LGL cells in LGL leukemia is not driven by the integration of a new infectious or endogenous retrovirus, although we do not rule out that these cells are responding to retroviral antigens produced in other cell types. However, our computational analyses revealed that the genomes of LGL leukemia patients carry a higher burden of polymorphic HERV-K proviruses compare to individuals from KGP of European ancestry. Our research emphasizes the merits of comprehensive genomic assessment of HERV-K in cancer samples and suggests that further analyses to determine contributions of HERV-K to LGL leukemia are warranted.

Exercise based cardiac rehabilitation (CR) is recognized internationally as a class 1 clinical practice recommendation for patients with select cardiovascular diseases and heart failure with reduced ejection fraction. Over the past decade, several meta-analyses have generated debate regarding the effectiveness of exercise-based CR for reducing all-cause and cardiovascular mortality. A common theme highlighted in these meta-analyses is the heterogeneity and/or lack of detail regarding exercise prescription methodology within CR programs. Currently there is no international consensus on exercise prescription for CR, and exercise intensity recommendations vary considerably between countries from light-moderate intensity to moderate intensity to moderate-vigorous intensity. As cardiorespiratory fitness [peak oxygen uptake (VO2peak)] is a strong predictor of mortality in patients with coronary heart disease and heart failure, exercise prescription that optimizes improvement in cardiorespiratory fitness and exercise capacity is a critical consideration for the efficacy of CR programming. This review will examine the evidence for prescribing higher-intensity aerobic exercise in CR, including the role of high-intensity interval training. This discussion will highlight the beneficial physiological adaptations to pulmonary, cardiac, vascular, and skeletal muscle systems associated with moderate-vigorous exercise training in patients with coronary heart disease and heart failure. Moreover, this review will propose how varying interval exercise protocols (such as short-duration or long-duration interval training) and exercise progression models may influence central and peripheral physiological adaptations. Importantly, a key focus of this review is to provide clinically-relevant recommendations and strategies to optimize prescription of exercise intensity while maximizing safety in patients attending CR programs.

Aims: The Baduanjin Eight-Silken-Movements wIth Self-Efficacy building for Heart Failure (BESMILE-HF) program is a contextually adapted cardiac rehabilitation program. It uses a traditional Chinese exercise, Baduanjin, to solve the unmet demand of exercise-based cardiac rehabilitation programs due to their scarcity and unaffordability in China. This pilot study assesses BESMILE-HF's feasibility and preliminary effects.Methods: Eighteen patients with chronic heart failure were included: 8 in a BESMILE-HF group (age: 67 ± 5 years, EF: 40.4 ± 13.6%) and 10 in a control group (age: 70 ± 13 years, EF: 42.9 ± 12.5%). Both received the usual medications, with the intervention group receiving additionally the BESMILE-HF program for 6 weeks. Feasibility was explored by participants' involvement in the intended intervention. Clinical outcome assessments were conducted at baseline and post-intervention, while adverse events were captured throughout the study period.Results: The BESMILE-HF program was well-received by patients, and adherence to the intervention was good. The intervention group completed all required home exercises and total home-practice time was correlated with baseline self-efficacy (r = 0.831, p = 0.011). Moreover, after 6 weeks, self-efficacy increased in the BESMILE-HF group (p = 0.028) and the change was higher than in the control [mean difference (MD): 3.2; 95% confidence interval (CI) 0.6–5.9, p = 0.004]. For the exercise capacity, the control group demonstrated a significant decline in peak oxygen consumption (p =0.018) whereas, the BESMILE-HF group maintained their exercise capacity (p = 0.063). Although the between-group difference was not statistically significance, there was clear clinical improvement in the BESMILE-HF group (1.5 mL/kg/min, 95% CI, −0.3 to 3.2 vs. minimal clinically important difference of 1 mL/kg/min). Throughout the study period, no adverse events related to the intervention were captured.Conclusions: BESMILE-HF is feasible for patients with chronic heart failure in Chinese settings. A larger sample size and a longer follow-up period is needed to confirm its benefit on clinical outcomes.Clinical Trial Registration:ClinicalTrials.gov: NCT03180320.

This 18-year cross-sectional study was conducted to provide data on the safety of exercise testing in the clinical Chinese population. We retrospectively identified exercise tests completed at Xiangya Hospital of Central South University from January 1, 2002 to December 31, 2019. From 43,130 unique individuals (50.9% female), a total of consecutive 50,142 tests (standard exercise testing 29,466; cardiopulmonary exercise testing 20,696) were retrieved. Demographics, patients' medical history, exercise testing characteristics, and exercise testing-related adverse events were described. Safety data is expressed as the number of adverse events per 10,000 tests, with 95% confidence interval. The average patients' age was 51 ± 13 years. The majority of patients were diagnosed with at least one disease (N = 44,941, 89.6%). Tests were maximal or symptom-limited. Common clinical symptoms included dizziness (6,822, 13.6%), chest pain or distress (2,760, 5.5%), and musculoskeletal limitations (2,507, 5.0%). Out of 50,142 tests, three adverse events occurred, including one sustained ventricular tachycardia, one sinus arrest with junctional escape rhythm at a rate of 28 bpm, and one syncopal event with fecal and urinary incontinence. The rate of adverse events was 0.8 events per 10,000 tests (95% confidence interval, 0.2–3.0) in men, 0.4 per 10,000 tests (0.7–2.2) in women, and 0.6 per 10,000 tests (0.21.8) total. This study represents the largest dataset analysis of exercise testing in the clinical Chinese population. Our results demonstrate that clinical exercise testing is safe, and the low rate of adverse events related to exercise testing might be due to the overall changes in clinical practice over time.

Abstract Introduction It remains unclear if naturally occurring respiratory muscle (RM) work influences leg diffusive O2 transport during exercise in heart failure patients with reduced ejection fraction (HFrEF). In this retrospective study, we hypothesized that RM unloading during submaximal exercise will lead to increases in locomotor muscle O2 diffusion capacity (DMO2) contributing to the greater leg VO2. Methods Ten HFrEF patients and 10 healthy control matched participants performed two submaximal exercise bouts (i.e., with and without RM unloading). During exercise, leg blood flow was measured via constant infusion thermodilution. Intrathoracic pressure was measured via esophageal balloon. Radial arterial and femoral venous blood gases were measured and used to calculate leg arterial and venous content (CaO2 and CvO2, respectively), VO2, O2 delivery, and DMO2. Results From CTL to RM unloading, leg VO2, O2 delivery, and DMO2 were not different in healthy participants during submaximal exercise (all, p > .15). In HFrEF, leg VO2 (CTL: 0.7 ± 0.3 vs. RM unloading: 1.0 ± 0.4 L/min, p

Purpose: The purpose of this study was to determine the effectiveness of a simple algorithm to mathematically predict a patients’ response to blood pressure (BP) therapy using functional genes in the 3 major organ systems involved in hypertension. Methods: Eighty-six patients with controlled hypertension completed 1 study visit consisting of a buccal swab collection, measurement of office BP, and a medical chart review for BP history. Genes in the analysis included 14 functional alleles in 11 genes. These genotypes were mathematically summed per organ system to determine whether a patient would likely respond to target therapy. Results: Patients recommended to and taking a diuretic had significantly higher rates of control (

Cardiac hemodynamic assessment during cardiopulmonary exercise testing (CPET) is proposed to play an important role in the clinical evaluation of individuals with cystic fibrosis (CF). Cardiac catheterization is not practical for routine clinical CPET. Use of oxygen pulse (O 2 pulse) as a noninvasive estimate of stroke volume (SV) has not been validated in CF. This study tested the hypothesis that peak exercise O 2 pulse is a valid estimate of SV in CF. Measurements of SV via the acetylene rebreathe technique were acquired at baseline and peak exercise in 17 mild-to-moderate severity adult CF and 25 age-matched healthy adults. We calculated O 2 p u l s e = V . O 2 H R . Baseline relationships between SV and O 2 pulse were significant in CF ( r = .80) and controls ( r = .40), persisting to peak exercise in CF ( r = .63) and controls ( r = .73). The standard error of estimate for O 2 pulse-predicted SV with respect to measured SV was similar at baseline (14.1 vs 20.1 mL) and peak exercise (18.2 vs 13.9 mL) for CF and controls, respectively. These data suggest that peak exercise O 2 pulse is a valid estimate of SV in CF. The ability to noninvasively estimate SV via O 2 pulse during routine clinical CPET can be used to improve test interpretation and advance our understanding of the impact cardiac dysfunction has on exercise intolerance in CF.

Large granular lymphocyte (LGL) leukemia is a chronic clonal lymphoproliferative disorder. Here, a T-LGL leukemia patient developed NK-LGL leukemia with residual leukemic T-LGL. TCRVβ usage and CDR3 sequence drifts were observed with disease progression. A STAT3 S614R mutation was identified in NK but not T-cells in the mixed leukemic stage. Multiple, non-dominant T-cell clones with distinct STAT3 mutations were present throughout. Our results suggest that T and NK-LGL leukemia may share common pathogenesis mechanisms and that STAT3 mutation alone is insufficient to bring about clonal expansion. Mutational and immunological monitoring may provide diagnostic and therapeutic significance in LGL leukemia.