INTRODUCTION: This study aimed to assess the impact of midline lumbar fusion with cortical bone trajectory screws (MIDLF/CBT) on the multifidus muscles, focusing on the evaluation of their postoperative atrophy. CLINICAL RATIONALE FOR THE STUDY: MIDLF/CBT is a relatively new technique increasingly used to treat spinal instability. Despite its reduced invasiveness compared to traditional posterior lumbar interbody fusion with traditional pedicle screws (PLIF/TP), concerns remain about potential damage to the multifidus muscles that are crucial for spinal stability. Understanding the extent of muscular atrophy post-MIDLF/CBT is vital for improving surgical outcomes, and potentially patient rehabilitation strategies. MATERIAL AND METHODS: This study retrospectively analysed preoperative and postoperative MRI scans of patients who underwent MIDLF/CBT for degenerative segmental spondylolisthesis. The bilateral width of the multifidus muscles at the operated segment and adjacent segments was measured using axial T2-weighted MRI scans. Statistical comparisons were made using a paired t test, with significance set at p < 0.05. RESULTS: The study included 16 patients with an average age of 57 ± 10 years, 10 of whom (62.5%) were women, and featured a mean follow-up period of 37 ± 25 months. Postoperative measurements showed a significant reduction in the width of the multifidus muscles at the operated segment (mean difference -3.3mm, p = 0.02) and the inferior adjacent segment (-7.4 mm, p < 0.01). A decrease in muscle width at the superior adjacent segment was also observed, although this was not statistically significant. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study concluded that MIDLF/CBT results in significant multifidus muscle atrophy at and below the operated segment, potentially impacting postoperative rehabilitation and recovery. These findings highlight the need for further research comparing MIDLF/CBT to other spinal stabilisation techniques. Additionally, incorporating functional electromyographic assessments of paraspinal muscles could provide deeper insights into the long-term consequences of spinal surgeries and helpdevelop new approaches and strategies to mitigate paravertebral muscles atrophy, thus enhancing patient outcomes.
- MeSH
- Lumbar Vertebrae * surgery diagnostic imaging MeSH
- Spinal Fusion * methods MeSH
- Paraspinal Muscles * diagnostic imaging pathology MeSH
- Cortical Bone surgery diagnostic imaging MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Pedicle Screws MeSH
- Postoperative Complications diagnostic imaging MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Spondylolisthesis * surgery diagnostic imaging MeSH
- Muscular Atrophy * etiology diagnostic imaging MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Skeletal muscle alterations are associated with higher mortality and morbidity in patients with liver cirrhosis. Assessing these changes seems to be a promising method for identifying patients at a high risk of poor outcomes following liver transplantation (LT). This is particularly important given the current global shortage of organ donors. However, evidence of the impact of these alterations on the prognosis of patients undergoing LT is inconclusive. The aim of our prospective study was to evaluate the impact of skeletal muscle changes, reflected in sarcopenia, myosteatosis and metabolic changes in the calf muscles, on perioperative outcomes and long-term survival after LT. We also sought to determine the posttransplant evolution of the resting muscle metabolism. METHODS: We examined 134 adult LT candidates. Of these, 105 underwent LT. Sarcopenia and myosteatosis were diagnosed by measuring the skeletal muscle index and mean psoas muscle radiation attenuation, respectively, which were obtained from computed tomography (CT) scans taken during pretransplant assessment. Additionally, patients underwent 31P MR spectroscopy (MRS) of the calf muscles at rest before LT and 6, 12 and 24 months thereafter. The median follow-up was 6 years. RESULTS: Patients with abnormal 31P MRS results and CT-diagnosed myosteatosis prior to LT had significantly worse long-term survival after LT (hazard ratio (HR), 3.36; 95% confidence interval (CI), 1.48-7.60; p = 0.0021 and HR, 2.58; 95% CI, 1.06-6.29; p = 0.03, respectively). Multivariable analysis showed that abnormal 31P MR spectra (HR, 3.40; 95% CI, 1.50-7.71; p = 0.003) were a better predictor of worse long-term survival after LT than myosteatosis (HR, 2.78; 95% CI, 1.14-6.78; p = 0.025). Patients with abnormal 31P MR spectra had higher blood loss during LT (p = 0.038), required a higher number of red blood cell transfusions (p = 0.006) and stayed longer in ICU (p = 0.041) and hospital (p = 0.007). Myosteatosis was associated with more revision surgeries following LT (p = 0.038) and a higher number of received red blood cell transfusion units (p = 0.002). Sarcopenia had no significant effect on posttransplant patient survival. An improvement in the resting metabolism of the calf muscles was observed at 12 and 24 months after LT. CONCLUSIONS: Abnormal 31P MRS results of calf muscles were superior to CT-based diagnosis of myosteatosis and sarcopenia in predicting perioperative complications and long-term survival after LT. Resting muscle metabolism normalized 1 year after LT in most recipients.
- MeSH
- Adult MeSH
- Muscle, Skeletal * diagnostic imaging metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy * methods MeSH
- Tomography, X-Ray Computed * methods MeSH
- Prognosis MeSH
- Prospective Studies MeSH
- Sarcopenia etiology metabolism MeSH
- Aged MeSH
- Liver Transplantation * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Preservation of mobility independence is a primary goal in older adults with physical frailty and sarcopenia (PF&S). Interventions based on the combination of physical activity (PA) and nutritional counselling have been indicated as strategies for the management of this condition, although their effectiveness is not confirmed in all investigations. A possible explanation for this uncertain scenario relies in the impact of the adherence to PA interventions. Hence, the present study investigated the impact of the adherence to PA sessions on the incidence of mobility disability in older adults with PF&S. METHODS: This is a secondary analysis of an evaluator blinded, randomised controlled trial, developed in 16 clinical sites across 11 European countries, from January 2016 to 31 October 2019. Participants were community-dwelling older adults (70+ years) with PF&S enrolled in the SPRINTT trial (NCT02582138). PF&S was operationalised as having a total score from 3 to 9 on the short physical performance battery (SPPB), low appendicular lean mass and ability to complete the 400-m walk test in < 15 min. Data from participants allocated to a multicomponent intervention (PA with technological support plus nutritional counselling) and a healthy ageing lifestyle education programme (control group) were analysed. Adherence to PA was assessed based on the number of weekly sessions attended. According to recommendations of the American College of Sports Medicine, adherence was categorised as below recommendations (< 2 sessions/week, BR), meeting recommendations (2-3 sessions/week, MR), and above recommendations (> 3 sessions/week, AR). The primary outcome was incident mobility disability, operationalised as incident inability to complete the 400-m walk test in < 15 min during up to 36 months of follow-up. RESULTS: Data of 1444 participants (mean age 79.3 years, 72.6% women) were analysed. In those with SPPB scores of 3-7, MR and AR groups had lower risk of mobility disability compared with controls [MR HR (95% CI): 0.57 (0.41-0.78), p = 0.001; AR HR (95% CI): 0.33 (0.23-0.46), p < 0.001] and BR groups [MR: HR (95% CI): 0.48 (0.34-0.69), p < 0.001; AR: HR (95% CI): 0.27 (0.18-0.38), p < 0.001] in a dose-dependent manner. In those with SPPB scores of 8 or 9, the BR group had a higher risk of mobility disability than controls. MR and AR groups had a lower risk of mobility disability than the BR group. CONCLUSIONS: In older adults with PF&S, adherence to PA recommendations is associated with lower incidence of mobility disability. This benefit depends on the degree of adherence as well as baseline physical performance. TRIAL REGISTRATION: ClinicalTrials.gov NCT02582138.
- MeSH
- Exercise * physiology MeSH
- Humans MeSH
- Mobility Limitation * MeSH
- Persons with Disabilities MeSH
- Sarcopenia * physiopathology therapy MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: Spatial navigation deficits are early symptoms of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for AD. This study investigated effects of APOE genotype on spatial navigation in biomarker-defined individuals with amnestic mild cognitive impairment (aMCI) and associations of AD biomarkers and atrophy of AD-related brain regions with spatial navigation. METHODS: 107 participants, cognitively normal older adults (CN, n = 48) and aMCI individuals stratified into AD aMCI (n = 28) and non-AD aMCI (n = 31) groups, underwent cognitive assessment, brain MRI, and spatial navigation assessment using the Virtual Supermarket Test with egocentric and allocentric tasks and a self-report questionnaire. Cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, phosphorylated tau181 and total tau) and amyloid PET imaging were assessed in aMCI participants. RESULTS: AD aMCI participants had the highest prevalence of APOE ε4 carriers and worst allocentric navigation. CSF levels of AD biomarkers and atrophy in AD-related brain regions were associated with worse allocentric navigation. Between-group differences in spatial navigation and associations with AD biomarkers and regional brain atrophy were not influenced by APOE genotype. Self-reported navigation ability was similar across groups and unrelated to spatial navigation performance. CONCLUSIONS: These findings suggest that allocentric navigation deficits in aMCI individuals are predominantly driven by AD pathology, independent of APOE genotype. This highlights the role of AD pathology as measured by biomarkers, rather than genetic status, as a major factor in navigational impairment in aMCI, and emphasizes the assessment of spatial navigation as a valuable tool for early detection of AD.
- MeSH
- Alzheimer Disease * genetics cerebrospinal fluid diagnostic imaging complications physiopathology pathology MeSH
- Amyloid beta-Peptides cerebrospinal fluid MeSH
- Apolipoprotein E4 * genetics MeSH
- Apolipoproteins E * genetics MeSH
- Atrophy MeSH
- Biomarkers cerebrospinal fluid MeSH
- Genotype MeSH
- Cognitive Dysfunction * genetics cerebrospinal fluid diagnostic imaging physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Brain pathology diagnostic imaging MeSH
- Neuropsychological Tests MeSH
- Peptide Fragments cerebrospinal fluid MeSH
- Positron-Emission Tomography MeSH
- Spatial Navigation * physiology MeSH
- tau Proteins cerebrospinal fluid MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Predicting and quantifying phenotypic consequences of genetic variants in rare disorders is a major challenge, particularly pertinent for 'actionable' genes such as thyroid hormone transporter MCT8 (encoded by the X-linked SLC16A2 gene), where loss-of-function (LoF) variants cause a rare neurodevelopmental and (treatable) metabolic disorder in males. The combination of deep phenotyping data with functional and computational tests and with outcomes in population cohorts, enabled us to: (i) identify the genetic aetiology of divergent clinical phenotypes of MCT8 deficiency with genotype-phenotype relationships present across survival and 24 out of 32 disease features; (ii) demonstrate a mild phenocopy in ~400,000 individuals with common genetic variants in MCT8; (iii) assess therapeutic effectiveness, which did not differ among LoF-categories; (iv) advance structural insights in normal and mutated MCT8 by delineating seven critical functional domains; (v) create a pathogenicity-severity MCT8 variant classifier that accurately predicted pathogenicity (AUC:0.91) and severity (AUC:0.86) for 8151 variants. Our information-dense mapping provides a generalizable approach to advance multiple dimensions of rare genetic disorders.
- MeSH
- Deep Learning * MeSH
- Child MeSH
- Adult MeSH
- Phenotype * MeSH
- Genetic Variation MeSH
- Genetic Association Studies MeSH
- Genomics methods MeSH
- Thyroid Hormones metabolism genetics MeSH
- Humans MeSH
- X-Linked Intellectual Disability genetics metabolism MeSH
- Adolescent MeSH
- Loss of Function Mutation MeSH
- Child, Preschool MeSH
- Monocarboxylic Acid Transporters * genetics metabolism MeSH
- Severity of Illness Index MeSH
- Muscular Atrophy genetics metabolism pathology MeSH
- Muscle Hypotonia genetics metabolism MeSH
- Symporters * genetics metabolism MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. HIGHLIGHTS: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.
Cerebellar atrophy is a characteristic sign of late-onset Tay-Sachs disease (LOTS). Other structural neuroimaging abnormalities are inconsistently reported. Our study aimed to perform a detailed whole-brain analysis and quantitatively characterize morphometric changes in LOTS patients. Fourteen patients (8 M/6F) with LOTS from three centers were included in this retrospective study. For morphometric brain analyses, we used deformation-based morphometry, voxel-based morphometry, surface-based morphometry, and spatially unbiased cerebellar atlas template. The quantitative whole-brain morphometric analysis confirmed the finding of profound pontocerebellar atrophy with most affected cerebellar lobules V and VI in LOTS patients. Additionally, the atrophy of structures mainly involved in motor control, including bilateral ventral and lateral thalamic nuclei, primary motor and sensory cortex, supplementary motor area, and white matter regions containing corticospinal tract, was present. The atrophy of the right amygdala, hippocampus, and regions of occipital, parietal and temporal white matter was also observed in LOTS patients in contrast with controls (p < 0.05, FWE corrected). Patients with dysarthria and those initially presenting with ataxia had more severe cerebellar atrophy. Our results show predominant impairment of cerebellar regions responsible for speech and hand motor function in LOTS patients. Widespread morphological changes of motor cortical and subcortical regions and tracts in white matter indicate abnormalities in central motor circuits likely coresponsible for impaired speech and motor function.
- MeSH
- Atrophy pathology MeSH
- White Matter * diagnostic imaging MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Brain pathology MeSH
- Retrospective Studies MeSH
- Tay-Sachs Disease * pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
SIGNIFICANCE STATEMENT: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS: The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS: Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 μ mol/L=0, K1: 250-450 μ mol/L=4, K2: >450 μ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS: The updated score optimizes clinicopathologic prognostication for clinical practice and trials.
- MeSH
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis * diagnosis MeSH
- Atrophy MeSH
- Fibrosis MeSH
- Creatinine MeSH
- Kidney MeSH
- Middle Aged MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Antibodies, Antineutrophil Cytoplasmic * MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Hypoglykémia v starobe je spojená s významnými chorobnosťami vedúcimi k fyzickej aj kognitívnej dysfunkcii. Opakované hospitalizácie v dôsledku častých hypoglykémií sú tiež spojené s ďalším zhoršovaním celkového zdravotného stavu pacientov. Tento negatívny vplyv hypoglykémie pravdepodobne nakoniec povedie ku krehkosti, invalidite. Zdá sa, že vzťah medzi hypoglykémiou a krehkosťou je obojsmerný a je sprostredkovaný radom vplyvov vrátane podvýživy. Preto je potrebné venovať pozornosť manažmentu podvýživy u geriatrických pacientov zlepšením energetického príjmu a udržaním svalovej hmoty. Dôležité je zamerať sa na zvýšenie fyzickej aktivity a konzervatívnejší prístup ku glykemickým cieľom u krehkých starších diabetikov.
Hypoglycemia in elderly is associated with significant morbidities leading to both physical and cognitive dysfunction. Repeated hospital admissions due to frequent hypoglycemia are also associated with further deterioration in patients’ general health. This negative impact of hypoglycemia is likely to eventually lead to frailty and disability. It appears that the relationship between hypoglycemia and frailty is bidirectional and mediated through a series of influences including under nutrition. Therefore, attention should be paid to the management of under nutrition in the general elderly population by improving energy intake and maintaining muscle mass. Increasing physical activity and having a more conservative approach to glycemic targets in frail geriatric patients with diabetes may be worthwhile.
An important complication of prolonged support of the left ventricle with an assist device when implanted in patients with heart failure is unloading-induced cardiac atrophy. Our recent study suggested that sex-linked differences in the development of atrophy induced by heterotopic heart transplantation (HTX) do exist, however, the role of the environmental conditions dependent on plasma concentrations of sex hormones remains elusive. We aimed to compare the course of HTX-induced cardiac atrophy in male and female rats after gonadectomy with substitution of steroid hormones of the opposite sex. In a separate series of experiments, we evaluated the course of unloading-induced cardiac atrophy in the female heart transplanted into a male recipient and vice versa. Cardiac atrophy was assessed as the ratio of the transplanted heart weight to native heart weight (HW), which was determined 14 days after HTX. In female rats, studied in both experimental variants, HTx resulted in significantly smaller decreases in whole HW when compared to those observed in male rats exposed to the same experimental conditions (-9 ± 1 and - 11 + 1 vs. -44 ± 2 and -42 ± 2 %, p?0.05 in both cases). The dynamic of changes in left and right ventricle was similar as in the whole HW. Our results show that the process of unloading-induced cardiac atrophy exhibits important sex-linked differences and that attenuation of this process in female rats cannot be simply ascribed to the protective effects of estradiol or to the absence of deleterious actions of testosterone. Keywords: Cardiac atrophy, Sex differences, Gonadectomy, Hormonal substitution, Heterotopic heart transplantation, Mechanical heart unloading.
- MeSH
- Atrophy * MeSH
- Estradiol blood MeSH
- Transplantation, Heterotopic * MeSH
- Rats MeSH
- Sex Characteristics * MeSH
- Gonadal Steroid Hormones * blood MeSH
- Rats, Wistar MeSH
- Heart MeSH
- Testosterone blood MeSH
- Heart Transplantation * adverse effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
