The effect of physical exercise on fatigue in systemic lupus erythematosus: a systematic review.

OBJECTIVE: Fatigue is a prominent and disabling manifestation that impairs the quality of life of Systemic Lupus Erythematosus (SLE) patients both physically and mentally. The majority of SLE patients reports fatigue as an unmet need. Physical exercise could help SLE patients to reduce fatigue and improve quality of life. METHODS: A systematic review was conducted to analyse the effectiveness of physical exercise interventions to reduce fatigue in SLE patients. PubMed, EMBASE, Web of Science: Core Collection, the Cochrane Library, CINAHL via EBSCO, and PEDro were searched (March 2021 to October 2021). Studies were included if they fulfilled prespecified criteria and were assessed for quality using the PEDro risk of bias tool. RESULTS: A total of 17 studies (11 RCTs, 3 non-RCTs, 2 one-group pretest-posttest designs, and 1 cross-sectional study) were included in this review. They compared exercise treatment with standard care, alternative treatment, or a different type of exercise. Most of the included studies reported significant improvement in fatigue after exercise therapy. However, study heterogeneity is an important methodological limitation. Exercise interventions did not cause disease flare-ups in patients with low to moderate disease activity. CONCLUSION: Studies are heterogeneous, precluding firm conclusions. In general, 10 out of 17 studies showed statistically significant but rarely clinically relevant improvement in fatigue after exercise treatment. However, results were not always consistent across different instruments used to assess fatigue. More multi-centred randomised controlled trials are needed to find the best type of physical activity that is both safe and effective for SLE patients.

Left atrial strain in patients after arterial switch operation for transposition of the great arteries.

BACKGROUND: Left atrial (LA) strain, comprising LA reservoir, conduit and contractile function could add mechanistic information of patients after arterial switch operation (ASO) for transposition of the great arteries (TGA). ASO patients might have abnormal ventriculoarterial coupling, which makes them vulnerable to left ventricle (LV) dysfunction and results in reduced exercise capacity. This explorative study aimed to evaluate the relation between LA strain, atrial size, ventricular function, and exercise data obtained by cardiopulmonary exercise testing (CPET). METHODS: In a cohort of 44 patients (71% male, mean age 25 ± 4 years) LA strain was measured using transthoracic speckle-tracking echocardiography. Further assessment involved standard echocardiography, CPET evaluation, and blood sampling. LA strain values were compared to normal values. Correlations were calculated. Regression analysis with all strain variables to the CPET data was performed. RESULTS: LA reservoir, conduit and contractile strain were normal in 30%, 89% and 50% of the patients, respectively. LA reservoir/contractile strain correlated to LV ejection fraction (ρ 0.310/-0.159, respectively) and LA reservoir/conduit strain correlated to the LA volume index (ρ 0.336/-0.357, respectively). None of the individual LA strain parameters were associated with the CPET variables. In multivariate regression analysis, LA contractile strain was significantly associated with the percentage of predicted maximal heart rate (ß - 2.555). CONCLUSIONS: These data suggest that in TGA patients after ASO repair LA strain is impaired and correlates with LA size and LV function. However, impaired LA strain wasn't associated with the standard CPET parameters. As such, clinical significance needs to be further unravelled.

Monitoring of Leukemia Clones in B-cell Acute Lymphoblastic Leukemia at Diagnosis and During Treatment by Single-cell DNA Amplicon Sequencing.

Acute lymphoblastic leukemia (ALL) is characterized by the presence of chromosomal changes, including numerical changes, translocations, and deletions, which are often associated with additional single-nucleotide mutations. In this study, we used single cell-targeted DNA sequencing to evaluate the clonal heterogeneity of B-ALL at diagnosis and during chemotherapy treatment. We designed a custom DNA amplicon library targeting mutational hotspot regions (in 110 genes) present in ALL, and we measured the presence of mutations and small insertions/deletions (indels) in bone marrow or blood samples from 12 B-ALL patients, with a median of 7973 cells per sample. Nine of the 12 cases showed at least 1 subclonal mutation, of which cases with PAX5 alterations or high hyperdiploidy (with intermediate to good prognosis) showed a high number of subclones (1 to 7) at diagnosis, defined by a variety of mutations in the JAK/STAT, RAS, or FLT3 signaling pathways. Cases with RAS pathway mutations had multiple mutations in FLT3, NRAS, KRAS, or BRAF in various clones. For those cases where we detected multiple mutational clones at diagnosis, we also studied blood samples during the first weeks of chemotherapy treatment. The leukemia clones disappeared during treatment with various kinetics, and few cells with mutations were easily detectable, even at low frequency (<0.1%). Our data illustrate that about half of the B-ALL cases show >2 subclones at diagnosis and that even very rare mutant cells can be detected at diagnosis or during treatment by single cell-targeted DNA sequencing.