Alteration of lumbar muscle morphology and composition in relation to low back pain: a systematic review and meta-analysis

BACKGROUND CONTEXTPrevious studies have proposed that there is a relationship between low back pain (LBP) and morphology and composition of paraspinal muscles. However, results have been conflicting, especially regarding fatty infiltration of muscles.PURPOSEThe primary goal of this study was to review and analyze results from imaging studies which investigated morphological and composition changes in the multifidus, erector spinae and psoas major muscles in people with LBP.STUDY DESIGN/SETTINGSystematic review with meta-analysis.PATIENT SAMPLEA patient sample was not requiredOUTCOME MEASURESThis review did not have outcome measures.METHODSPubMed, Scopus, Web of Sciences, EMBASE and ProQuest were searched for eligible studies up to 31st July 2020 (all languages). A systematic search of electronic databases was conducted to identify studies investigating the association between the morphology and fat content of lumbar muscles in people with LBP compared with a (no LBP) control group. 13,795 articles were identified. Based on the screening for inclusion/ exclusion, 25 were included. The quality of the studies was evaluated using the Newcastle-Ottawa Scale. From the 25 articles, 20 were included in the meta-analysis.RESULTSResults showed that the total cross-sectional area of the multifidus was smaller in people with LBP (Standardized mean difference, SMD = -0.24, 95% CI = -0.5 to 0.03). Combined SMDs showed a medium effect of LBP on increasing multifidus muscle fat infiltration (SMD = 0.61, 95% CI = 0.30 to 0.91). There were no LBP related differences identified in the morphology or composition of the lumbar erector spine and psoas major muscles.CONCLUSIONSPeople with LBP were found to have somewhat smaller multifidus muscles with a significant amount of intramuscular fat infiltration. Varying sample size, age and BMI of participants, quality of studies and the procedures used to measure fat infiltration are possible reasons for inconsistencies in results of previous studies.     

Synergism through combination of chemotherapy and oxidative stress-induced autophagy in A549 lung cancer cells using redox-responsive nanohybrids: A new strategy for cancer therapy

A combination of various therapeutic approaches has emerged as a promising strategy for cancer treatment. A safe and competent nano-delivery system is thus in urgent demand to facilitate the simultaneous transport of various therapeutic agents to cancer cells and a tumor region to achieve synergistic effect. Gold nanoparticles (GNPs) and mesoporous silica nanoparticle (MSNs) were fabricated herein as potential candidates for drug delivery. Serving as gatekeepers, GNPs (5 nm in diameter) were attached onto the amino-functionalized MSNs (denoted as NMSNs) via a relatively weak gold–nitrogen bonding. The resulting nanohybrids (denoted as GCMSNs) were uptaken by cells, and the detachment of GNPs and subsequent intracellular drug release from NMSNs were achieved by competitive binding of intracellular glutathione to GNPs. In addition to the function of gatekeeping, GNPs also play another role as the oxidative stress elicitor. Our in vitro studies revealed that GCMSNs induced higher oxidative stress in lung cancer cells (A549) than in normal cells (3T3-L1). This growth inhibitory effect found in the cancer cells was likely induced by mitochondria dysfunction originated from the GCMSN-induced, oxidative stress-triggered mitochondria-mediated autophagy. The redox-responsive nanohybrids were further loaded with camptothecin and the intensified synergistic therapeutic effects were observed associated with combined chemotherapy and oxidative stress strategy. The results clearly demonstrate that such unique nanohybrids hold great promise for selective and effective cancer treatments.     

Increased LDL electronegativity in chronic kidney disease disrupts calcium homeostasis resulting in cardiac dysfunction

Chronic kidney disease (CKD), an independent risk factor for cardiovascular disease, is associated with abnormal lipoprotein metabolism. We examined whether electronegative low-density lipoprotein (LDL) is mechanistically linked to cardiac dysfunction in patients with early CKD. We compared echocardiographic parameters between patients with stage 2 CKD (n = 88) and normal controls (n = 89) and found that impaired relaxation was more common in CKD patients. Reduction in estimated glomerular filtration rate was an independent predictor of left ventricular relaxation dysfunction. We then examined cardiac function in a rat model of early CKD induced by unilateral nephrectomy (UNx) by analyzing pressure–volume loop data. The time constant of isovolumic pressure decay was longer and the maximal velocity of pressure fall was slower in UNx rats than in controls. When we investigated the mechanisms underlying relaxation dysfunction, we found that LDL from CKD patients and UNx rats was more electronegative than LDL from their respective controls and that LDL from UNx rats induced intracellular calcium overload in H9c2 cardiomyocytes in vitro. Furthermore, chronic administration of electronegative LDL, which signals through lectin-like oxidized LDL receptor-1 (LOX-1), induced relaxation dysfunction in wild-type but not LOX-1^−/− mice. In in vitro and in vivo experiments, impaired cardiac relaxation was associated with increased calcium transient resulting from nitric oxide (NO)-dependent nitrosylation of SERCA2a due to increases in inducible NO synthase expression and endothelial NO synthase uncoupling. In conclusion, LDL becomes more electronegative in early CKD. This change disrupts SERCA2a-regulated calcium homeostasis, which may be the mechanism underlying cardiorenal syndrome.     

Renal Dysfunction is the Strongest Prognostic Factor After Carotid Artery Stenting According to Real-World Data

PurposeThrough the progression of devices, the adaptation of carotid artery stenting (CAS) has been expanded according to the non-inferiority of CAS for carotid endarterectomy reported by several randomized control trials. To maintain favorable outcomes, identifying prognostic factors is essential for optimizing treatment indications and periprocedural management. This study focused on the prognostic factors of CAS using real-world data.MethodsThis retrospective multicenter cohort study aimed to identify the prognostic factors after CAS using real-world data from the stroke registry of Yokohama (STrOke Registry of Yokohama; STORY) from January 1, 2018 to May 31, 2021. Patient characteristics, procedural factors, complications, and prognoses were collected using medical records.ResultsData from 107 patients were enrolled in this study after excluding those with insufficient data (2 cases). The mean participant age was 74.9±8.2 years, and 66 patients (61.7%) were symptomatic. Symptomatic lesions were a significant prognostic factor in the overall analysis (p=0.003). A multivariate analysis showed that the estimated glomerular filtration rate (eGFR) (odds ratio: 1.11, p=0.003) and staged CAS (odds ratio: 38.9, p=0.04) were independent prognostic factors. The odds ratio and relative risk of mRS deterioration when eGFR was under 49 mL/min/1.73 m² compared with when eGFR was above 49 mL/min/1.73 m² were 5.2 and 3.74, respectively.ConclusionsIn this real-world multicenter study, we established independent prognostic factors for CAS using high totality data. For patients with symptomatic lesions and low eGFR (≤49 mL/min/1.73 m²), indication for treatment should be considered strictly.