K. Batten, Australia
N. Van Doorn, J. H. Moon, D. Simar,et al

JIMD Rep 2026 Vol. 67 Issue 5 Pages e70123
https://www.ncbi.nlm.nih.gov/pubmed/42781531

Glycogen storage disease VII (GSD VII), also known as Tarui disease, is caused by a deficiency of the skeletal muscle enzyme, phosphofructokinase (PFK). Classical GSD VII is characterised by reduced exercise capacity and exercise-induced myopathic symptoms, exacerbated with carbohydrate intake. No recommended medical or dietary therapy currently exists to improve exercise symptomology in GSD VII. An 11-year-old female was recommended four trial dietary therapies for 8 weeks each: (1) usual diet, (2) 150 mg/kg exogenous ketones pre-exercise, (3) modified Atkins diet (MAD), (4) MAD and pre-exercise ketones. Clinical assessments comprised cardiopulmonary exercise test, anthropometry, biochemical tests including creatine kinase (CK), quality of life (QoL), heart rate (HR) monitoring and subjective symptom reports. Exogenous ketones improved exercise capacity demonstrated by reduced HR for equivalent exercise workload, and participation in higher intensity exercise for longer duration. MAD improved QoL physical domain score by 29%, normalised CK and halved the number of symptoms reported per ‘physically active day’. Dissatisfaction with MAD resulted in unintentional weight loss, and a 20% reduction in QoL emotional domain score, leading to the patient declining the fourth study phase. This study is the first to demonstrate a beneficial effect of exogenous ketones, and separately, MAD, in a child with GSD VII. Exogenous ketones or MAD could be recommended under medical and dietetic supervision in GSD VII. However, consideration must be given to the potential negative impact of MAD on weight and emotional health. Further interventional studies are warranted in this condition.

O. K. Nordfonn,  Department of Heart Disease,Bergen,  Norway,
K. Johnsen Ramstad, T. Roed Pettersen,et al

JMIR Cardio 2026 Vol. 10 Pages e93398

BACKGROUND: Cardiac rehabilitation (CR) is a class IA-recommended treatment and secondary preventive strategy for people with coronary artery disease. eHealth solutions show promise in providing accessible CR. However, few provide a comprehensive and multimodal CR program, and most programs are developed without input from end users.
OBJECTIVE: The aim of this study was to provide a detailed description of the multidisciplinary co-creation process used to develop a person-centered, multimodal digital CR program that integrated the perspectives of stakeholders and end users throughout, with the rationale to optimize the acceptance and feasibility of the CR program.
METHODS: We incorporated a user-centered design with a 3-phase, iterative, multidisciplinary stakeholder co-creation process. This included defining needs (phase 1), development and refinement (phase 2), and testing and optimization (phase 3). Overall, 26 internal stakeholders from the project team participated, including clinicians, researchers, software developers, and user representatives. In addition, 35 external stakeholders (20 clinicians and 15 people with cardiac-related problems) participated in a user-centered development process that included workshops, intervention content development, and usability testing. Data were collected through contextual inquiry, 4 workshops with stakeholders, 12 co-creation sessions with user representatives, 2 usability testing sessions using a think-aloud methodology, standardized usability surveys, and individual and focus group interviews. Intervention content was developed and finalized based on existing evidence, stakeholder input, and user testing. A smoke test and a minimum viable product test were conducted. Data were analyzed using rapid qualitative content analysis and descriptive statistics.
RESULTS: Analyses of data gathered across the 3 phases identified 5 themes important to stakeholders and end users: a program with (1) personalized and tailored solutions with reliable, trustworthy, and evidence-based content (ie, a face-to-face introduction session at the start of the program and a tailored registration page to individually register personal risk factors, goals, and medications); (2) options for feedback (ie, an asynchronous messaging service and tailored face-to-face video consultations with clinicians); (3) peer support (ie, exercise sessions in groups); (4) digital reminders (ie, notifications on a smartphone or tablet); and (5) motivational features (ie, interactive cardiac-specific learning modules on coronary artery disease and secondary prevention). Evidence-based content development resulted in 9 cardiac-specific interactive learning modules, a module for personal health data entry, live exercise sessions, tailored digital follow-up, and an asynchronous messaging service. Readability was assessed using the Gunning Fog Index, with levels ranging from 4 to 13. The overall System Usability Scale score was 86.2 (SD 12.2), indicating excellent usability.
CONCLUSIONS: A multidisciplinary stakeholder co-creation process combining well-known evidence-based concepts with stakeholder input identified several areas for improvement and facilitated the development of the digital CR program. Contextually tailored, co-designed interventions may improve relevance and responsiveness to user needs. The feasibility and effectiveness of the program will be further evaluated in the eCardiacRehab trial.

Byandova A; Plovdiv, Bulgaria.
Marinov B

Folia Medica (Plovdiv). 68(4), 2026 Aug 20.

No abstract available

Mima H; Osaka Graduate School of Medicine Osaka Japan.
Sera F; Ohtani T; Akazawa Y; et al

Journal of the American Heart Association. 15(17):e050214, 2026 Sep.

BACKGROUND: In nonischemic cardiomyopathy, the clinical relevance of
decreased resting myocardial technetium-99m sestamibi (99mTc-MIBI) uptake
regarding exercise capacity and clinical outcomes remains incompletely
understood. We investigated whether decreased 99mTc-MIBI uptake is
associated with impaired exercise capacity and adverse clinical outcomes
in nonischemic cardiomyopathy.

METHODS: We retrospectively analyzed 182 patients (mean age 51.4+/-14.0
years; 27% female) with nonischemic cardiomyopathy and left ventricular
ejection fraction <50% who underwent 99mTc-MIBI scintigraphy and
cardiopulmonary exercise testing from 2016 to 2023. Myocardial uptake of
99mTc-MIBI was evaluated using the summed rest score (SRS). Exercise
capacity was assessed by percentage of predicted peak oxygen consumption
(PPVO2), with <=60% defining impairment.

RESULTS: Seventy-four patients (41%) had PPVO2 <=60% and higher SRS
(median: 12 versus 8; P < 0.001). Higher SRS remained significantly
associated with PPVO2 <=60% after adjustment for relevant clinical
covariates, including brain natriuretic peptide level, left ventricular
ejection fraction, and heart failure duration. Over a median follow-up of
807 days, 23 patients (13%) experienced the composite outcome of all-cause
death, ventricular assist device implantation, or heart transplantation.
Higher SRS was associated with composite outcomes after adjusting for
PPVO2 <=60%. Among the 4 groups stratified by median SRS of 9 and PPVO2 of
60%, patients with high SRS and low PPVO2 had the highest incidence of
adverse events.

CONCLUSIONS: Decreased myocardial 99mTc-MIBI uptake was associated with
impaired exercise capacity and adverse outcomes in patients with
nonischemic cardiomyopathy. Our findings suggest that myocardial injury
assessment using 99mTc-MIBI scintigraphy may provide prognostic
information complementary to exercise capacity.

Zubac D; Center for Integrated Oncology Aachen, Germany
Sonntag T; Kranjc D; Baumann FT

Physiological Reports. 14(17):e71090, 2026 Sep.

This study examined whether cardiopulmonary exercise test (CPET)
performance parameters are associated with chronic cancer-related fatigue
in patients receiving immunotherapy checkpoint inhibitors (ICI) and
healthy controls. Also, the differences in energy expenditure of
steady-state cycling and gross efficiency were assessed during submaximal
cycling efforts. This study involved patients (n = 19, 48 +/- 13 years)
receiving PD-1, PD-L1 checkpoint inhibitors and controls of similar age (n
= 21, 49 +/- 17 years). During the first visit, data on medical history,
previous physical activity records, and CPET to voluntary exhaustion were
collected. The second visit involved body composition assessment, the
MFI-20 fatigue questionnaire, and 30-min steady-state cycling at 90% gas
exchange threshold. There were no significant differences observed between
the groups in age, stature, BMI, or resting blood pressure. Peak VO2 was
33% lower, and the group under ICI treatment had lower cycling efficiency
(22.49% vs. 20.07%, p = 0.031), compared to controls. All self-reported
fatigue items derived from MFI-20 were significantly higher in the ICI
group compared to controls (p = 0.001). The regression analysis found no
association between the self-reported general fatigue and data collected
during CPET. Patients under ICI treatment reported higher levels of
chronic fatigue, lower peak VO2, and reduced cycling efficiency.
Interestingly, variables collected during CPET did not explain
self-reported chronic fatigue, underlying the complexity of this
phenomenon.

Wu X; Harbin Medical University, Heilongjiang, China.
Cui H; Wang S; Zheng X; et al

Clinical & Experimental Medicine. 26(1), 2026 Jun 22.

Heart failure after acute myocardial infarction (post-MI HF) has become a
major global health problem. Accurate risk prediction is essential for
optimising management and preventing post-MI HF. However, existing models
rely mainly on resting-state clinical examinations and inadequately
reflect the complex pathophysiology of post-MI HF. We aimed to develop and
validate a multimodal machine learning (ML) model incorporating
cardiopulmonary exercise testing (CPET) data to predict post-MI HF risk
and to quantify CPET’s incremental value. This study included 3172 acute
myocardial infarction (AMI) patients who underwent CPET at three hospitals
from 2018 to 2023. The primary outcome was post-MI HF within 1 year.
Thirteen ML algorithms were used to select clinical and CPET variables and
to construct multimodal prediction models. The incremental predictive
value of CPET was evaluated by the area under the curve (AUC), integrated
discrimination improvement index (IDI), and net reclassification
improvement index (NRI). After screening, 2221 patients were included, of
whom 221 (10.0%) developed post-MI HF. The optimal multimodal ML model
achieved an AUC of 0.987 (95% CI: 0.982-0.992) in training set and 0.929
(95% CI: 0.903-0.955) in external validation set. Ablation analyses showed
that CPET significantly improved discrimination (AUC: 0.890 vs. 0.929,
P=0.003), calibration (IDI=0.135 [95% CI: 0.082-0.189], P<0.001), and
reclassification (NRI=0.154 [95% CI: 0.073-0.234], P<0.001). The model
effectively stratified low- and high-risk patients (3.1% vs. 54.7%,
P<0.001). The multimodal ML model accurately predicted post-MI HF and
highlighted the additive value of CPET in risk stratification. The
web-based risk calculator derived from this model may support early
identification of high-risk patients and facilitate personalised
management.

de Almeida IS; Centro Infant, Rio Grande do Sul, Brazil
Vendrusculo FM; da Costa MS; Donadio MVF

Pediatric Pulmonology. 61(9):e71826, 2026 Sep.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR)
modulator therapy has led to relevant clinical advances in people with
cystic fibrosis (pwCF). However, its effects on aerobic fitness are
unclear.

OBJECTIVE: To evaluate the effects of CFTR modulator therapy on aerobic
fitness in pwCF through a systematic review and meta-analysis.

METHODS: This systematic review (CRD420251066602) was conducted by
searching major databases without date or language restrictions.
Analytical studies evaluating cardiopulmonary exercise testing outcomes
before and after CFTR modulator therapy were included. The primary outcome
was peak oxygen uptake (peak VO2). Secondary outcomes included peak VO2 (%
predicted), VO2 at the first ventilatory threshold (VT1), breathing
reserve, workload, forced expiratory volume in one second (FEV1), and body
mass index. Meta-analyses were performed using a random-effects model with
heterogeneity assessed by the I2 statistic, and sensitivity analyses
conducted.

RESULTS: Thirteen studies (n = 578 participants) were included, of which
11 were eligible for meta-analysis. The meta-analysis did not identify a
significant improvement in peak VO2 (mL.kg-1.min-1) after CFTR modulator
use (MD = -0.22; 95% CI: -2.10 to 1.65; p = 0.82). For submaximal
outcomes, after sensitivity analysis, VO2 at VT1 was significantly lower
in the post-intervention period (MD = -1.85; 95% CI: -2.61 to -1.10; p <
0.00001). Breathing reserve increased significantly (MD = 7.94; 95% CI:
2.15 to 13.73; p = 0.007), and workload also increased significantly (MD =
15.39; 95% CI: 2.20 to 28.58; p = 0.02).

CONCLUSION: CFTR modulator therapy is not consistently associated with
improvements in aerobic fitness, as assessed by peak VO2, although it
appears to variably influence outcomes related to ventilatory response and
exercise performance.

James MD; Department of Medicine, Kingston General
Hospital, Kingston, ON, Canada. & other Canadian sites
Vincent SG; Elbehairy AF; Phillips DB; et al

Copd: Journal of Chronic Obstructive Pulmonary Disease. 23(1):2705831,
2026 Jul 25.

Long-term smokers with persistent dyspnoea and exercise intolerance, who
are at risk for COPD, require careful clinical assessment. However, many
such individuals have only minor abnormalities on spirometry, and it is
not known if various additional tests of small airways dysfunction (SAD)
or pulmonary microvascular deficits, offer added clinical value. In this
study we wished to determine which of the available resting pulmonary
function tests (e.g. airway mechanics and lung diffusing capacity for
carbon monoxide, DLCO) best uncover the physiological underpinnings of
these troublesome respiratory symptoms. This tri-centre, prospective study
enrolled 90 volunteers: 33 non-smoker controls, 57 symptomatic smokers, 38
of whom had Global Initiative for Obstructive Lung Disease Grade 1 COPD).
Participants completed impulse oscillometry (IOS), spirometry, body
plethysmography, DLCO, single and multiple breath nitrogen washout and an
incremental cycle cardiopulmonary exercise test. Smokers had more diverse
physiological abnormalities, greater dyspnoea and exercise intolerance
than healthy controls. Stepwise multilinear regression revealed that DLCO
was the only independent predictor of dyspnoea burden (ratio of peak
dyspnoea score to peak oxygen uptake (VO2peak)), lower VO2peak, higher
ventilatory equivalent for carbon dioxide (VE/VCO2 nadir) and dynamic
inspiratory mechanical constraints (higher tidal volume to inspiratory
capacity ratio), after accounting for age, sex, height, and smoking
history. In symptomatic smokers, reduced DLCO, contributed more to the
variance in exertional dyspnoea and exercise intolerance than all airway
mechanical measurements. This attests to the added value of DLCO for
clinicians assessing the nature and extent of smoking-related lung injury
in individuals with only minor airway obstruction.

Johansen SH; Faculty of Medicine, University of Oslo, Oslo, Norway.
Edvardsen E; Raastad T; Ruud E;et al

Pediatric Blood & Cancer. 73(9):e70478, 2026 Sep.

BACKGROUND: Fatigue is a prevalent and distressing late effect among
childhood cancer survivors (CCSs), yet its physiological determinants
remain unclear. This study examined the associations between physical
fitness (VO2peak and muscular strength), physical function (sit-to-stand
[STS] performance), physical activity, and fatigue in adolescent CCSs, and
whether these associations differ from those observed in healthy controls.

METHODS: This cross-sectional analysis was part of the international
multicenter Physical Activity and Fitness in Childhood Cancer Survivors
(PACCS) study, including CCSs and age- and sex-matched healthy controls.
Fatigue was assessed using the Pediatric Quality of Life
Inventory-Multidimensional Fatigue Scale. Physical fitness and function
were evaluated by cardiopulmonary exercise testing (VO2peak), isometric
muscular strength (knee extension, chest press, and handgrip), and the
1-min STS test. Physical activity was measured by accelerometry.
Associations between physical fitness, physical activity, and fatigue were
examined using multivariable mixed-effects linear regression models.

RESULTS: A total of 123 CCSs (mean age 13.5 +/- 2.5 years, 6.7 +/- 3.5
years posttreatment) and 99 controls (mean age 13.1 +/- 2.6 years) were
included. Total fatigue scores among CCSs and controls were 72.6 +/- 17.1
and 74.8 +/- 15.7, respectively (p = 0.324). Higher VO2peak (beta = 0.66,
95% confidence interval [CI] 0.14-1.17, p = 0.012) and greater muscular
strength (beta = 5.85, 95% CI 0.63-11.08, p = 0.028) were associated with
less fatigue in CCSs, whereas activity levels were not associated with
fatigue. No significant differences were observed in the association of
physical fitness or physical activity measures with fatigue between CCSs
and controls.

CONCLUSION: Higher physical fitness, but not physical activity level, was
associated with lower fatigue in adolescent CCSs, with similar
associations observed in healthy controls. These findings highlight
physical fitness as a potential target for fatigue management in
adolescent CCSs.

Szulc AM; Faculty of Health Sciences and Physical Education, Bydgoszcz, Poland
Balatoni I; Przybylski G; Chesy A; Busko K

British Journal of Sports Medicine. 60(16):1250-1258, 2026 Aug 16.

PURPOSE: Research on deaf and hard-of-hearing athletes suggests
sensorimotor trade-offs from neuroplasticity. We tested divergent
adaptation in elite female soccer players, hypothesising a phenotype with
cardiorespiratory/repeated-sprint deficits with enhanced explosive power
(H1), respiratory-perceptual fatigue (H2) and a sensory-endurance gradient
(H3).

METHODS: This cross-sectional study compared 18 elite deaf (Polish
National Team) and 21 hearing (top-tier) players. Assessments included
cardiopulmonary exercise testing with maximal oxygen uptake (VO2max)
verification, Running-Based Anaerobic Sprint Test (RAST) and
countermovement jump (CMJ) with allometric scaling. Analysis of covariance
controlled for body fat and training experience.

RESULTS: Supporting H1, hearing athletes had higher adjusted VO2max (50.3
vs 45.8 mL/kg/min, p=0.016) and RAST peak power (7.2 vs 6.1 W/kg,
p<0.001), while deaf athletes generated greater allometrically scaled CMJ
peak power (115.8 vs 107.4, p=0.011). Supporting H2, deaf athletes had
shorter time to exhaustion (TTE) (12.35 vs 14.83 min, p<0.001) and lower
attainment of respiratory exchange ratio >1.0 (33% vs 90%, p=0.0002), with
dyspnoea cited as the limiting symptom (56% deaf vs 71% leg fatigue in
hearing). Partially supporting H3, deeper hearing loss correlated with
shorter TTE (r=-0.64, p=0.005) but not CMJ power.

CONCLUSIONS: Findings evidence a neuro-respiratory trade-off in elite
deaf female soccer players: cardiorespiratory and repeated-sprint deficits
with an explosive power advantage. Fatigue appears governed by
respiratory-perceptual factors rather than metabolic acidosis. This
phenotype, likely from developmental neuroplasticity, necessitates
individualised dual-track training.