Functional Recovery and Serum Angiogenin Changes According to Intensity of Rehabilitation Therapy After Stroke

Angiogenina; Terapia intensiva; RehabilitaciónAngiogenin; Intensive therapy; RehabilitationAngiogenina; Teràpia intensiva; RehabilitacióBackground: Rehabilitation is still the only treatment available to improve functional status after the acute phase of stroke. Most clinical guidelines highlight the need to design rehabilitation treatments considering starting time, intensity, and frequency, according to the tolerance of the patient. However, there are no homogeneous protocols and the biological effects are under investigation. Objective: To investigate the impact of rehabilitation intensity (hours) after stroke on functional improvement and serum angiogenin (ANG) in a 6-month follow-up study. Methods: A prospective, observational, longitudinal, and multicenter study with three cohorts: strokes in intensive rehabilitation therapy (IRT, minimum 15 h/week) vs. conventional therapy (NO-IRT, <15 h/week), and controls subjects (without known neurological, malignant, or inflammatory diseases). A total of seven centers participated, with functional evaluations and blood sampling during follow-up. The final cohort includes 62 strokes and 43 controls with demographic, clinical, blood samples, and exhaustive functional monitoring. Results: The median (IQR) number of weekly hours of therapy was different: IRT 15 (15–16) vs. NO-IRT 7.5 (5–9), p < 0.01, with progressive and significant improvements in both groups. However, IRT patients showed earlier improvements (within 1 month) on several scales (CAHAI, FMA, and FAC; p < 0.001) and the earliest community ambulation achievements (0.89 m/s at 3 months). There was a significant difference in ANG temporal profile between the IRT and NO-IRT groups (p < 0.01). Additionally, ANG was elevated at 1 month only in the IRT group (p < 0.05) whereas it decreased in the NO-IRT group (p < 0.05). Conclusions: Our results suggest an association of rehabilitation intensity with early functional improvements, and connect the rehabilitation process with blood biomarkers.NG-R holds a VHIR fellowship and MO-G a Joan Margarit VHIR fellowship. Research grants: from the Instituto de Salud Carlos III and European Regional Development Funds (PI16/00981, PI19/00186, RD16/0019/0021, and RD16/0019/0008), 2017-SGR-1427 program from the Generalitat de Catalunya-AGAUR, and Clinical Translational Program for Regenerative Medicine in Catalonia (P-CMR [C])

Functional Recovery and Serum Angiogenin Changes According to Intensity of Rehabilitation Therapy After Stroke

Rehabilitation is still the only treatment available to improve functional status after the acute phase of stroke. Most clinical guidelines highlight the need to design rehabilitation treatments considering starting time, intensity, and frequency, according to the tolerance of the patient. However, there are no homogeneous protocols and the biological effects are under investigation. To investigate the impact of rehabilitation intensity (hours) after stroke on functional improvement and serum angiogenin (ANG) in a 6-month follow-up study. A prospective, observational, longitudinal, and multicenter study with three cohorts: strokes in intensive rehabilitation therapy (IRT, minimum 15 h/week) vs. conventional therapy (NO-IRT, <15 h/week), and controls subjects (without known neurological, malignant, or inflammatory diseases). A total of seven centers participated, with functional evaluations and blood sampling during follow-up. The final cohort includes 62 strokes and 43 controls with demographic, clinical, blood samples, and exhaustive functional monitoring. The median (IQR) number of weekly hours of therapy was different: IRT 15 (15-16) vs. NO-IRT 7.5 (5-9), p < 0.01, with progressive and significant improvements in both groups. However, IRT patients showed earlier improvements (within 1 month) on several scales (CAHAI, FMA, and FAC; p < 0.001) and the earliest community ambulation achievements (0.89 m/s at 3 months). There was a significant difference in ANG temporal profile between the IRT and NO-IRT groups (p < 0.01). Additionally, ANG was elevated at 1 month only in the IRT group (p < 0.05) whereas it decreased in the NO-IRT group (p < 0.05). Our results suggest an association of rehabilitation intensity with early functional improvements, and connect the rehabilitation process with blood biomarkers

Contribution of molecular analysis to the typification of the non-functioning pituitary adenomas.

The WHO Classification of Tumours of Endocrine Organs considers the inmunohistochemical characterization of pituitary adenomas (PA) as mandatory for patient diagnosis. Recent advances in the knowledge of the molecular patterns of these tumours could complement this classification with gene expression profiling.Within the context of the Spanish Molecular Registry of Pituitary Adenomas (REMAH), a multicentre clinical-basic research project, we analysed the molecular phenotype of 142 PAs with complete IHC and clinical information. Gene expression levels of all pituitary hormones, type 1 corticotrophin-releasing hormone receptor, dopamine receptors and arginine vasopressin receptor 1b were measured by quantitative real-time polymerase chain reaction. In addition, we used three housekeeping genes for normalization and a pool of nine healthy pituitary glands from autopsies as calibration reference standard.Based on the clinically functioning PA (FPA: somatotroph, corticotroph, thyrotroph and lactotroph adenomas), we established the interquartile range of relative expression for all genes studied in each PA subtype. That allowed molecularly the different PA subtypes, including the clinically non-functioning PA (NFPA). Afterwards, we estimated the concordance of the molecular and immunohistochemical classification with clinical diagnosis in FPA and between them in NFPA. The kappa values were higher in molecular than in immunohistochemical classification in FPA and showed a bad concordance in all NFPA subtypes.According to these results, the molecular characterization of the PA complements the IHC analysis, allowing a better typification of the NFPA

Relative gene expression of hormone and receptor implicated in the molecular classification of pituitary adenomas (n = 142).

<p>Figure shows the bar chart of the gene expression levels analyzed for each subtype. Silent lactotroph and silent somatotroph are not represented because there was none in our series.</p

Concordance between clinical diagnosis and independent diagnosis with each technique.

<p>Concordance between clinical diagnosis and independent diagnosis with each technique.</p

Concordance between immunohistochemical and molecular classifications for the 74 clinically NFPA.

<p>Concordance between immunohistochemical and molecular classifications for the 74 clinically NFPA.</p

Prevalence of the different pituitary subtypes according to their inmunohistochemical or molecular identification in the series studied (N = 142).

<p>Prevalence of the different pituitary subtypes according to their inmunohistochemical or molecular identification in the series studied (N = 142).</p

Clinical Baseline characteristics of patients.

<p>Clinical Baseline characteristics of patients.</p

Ranges of relative expression (p25-p75) of the pituitary genes.

<p>Ranges of relative expression (p25-p75) of the pituitary genes.</p