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Journal of Cachexia, Sarcopenia and... Apr 2024Cachexia, with weight loss (WL) as a major component, is highly prevalent in patients with cancer and indicates a poor prognosis. The primary objective of this study was... (Review)
Review
Cachexia, with weight loss (WL) as a major component, is highly prevalent in patients with cancer and indicates a poor prognosis. The primary objective of this study was to conduct a meta-analysis to estimate the risk of mortality associated with cachexia (using established WL criteria prior to treatment initiation) in patients with non-small-cell lung cancer (NSCLC) in studies identified through a systematic literature review. The review was conducted according to PRISMA guidelines. Embase® and PubMed were searched to identify articles on survival outcomes in adult patients with NSCLC (any stage) and cachexia published in English between 1 January 2016 and 10 October 2021. Two independent reviewers screened titles, abstracts and full texts of identified records against predefined inclusion/exclusion criteria. Following a feasibility assessment, a meta-analysis evaluating the impact of cachexia, defined per the international consensus criteria (ICC), or of pre-treatment WL ≥ 5% without a specified time interval, on overall survival in patients with NSCLC was conducted using a random-effects model that included the identified studies as the base case. The impact of heterogeneity was evaluated through sensitivity and subgroup analyses. The standard measures of statistical heterogeneity were calculated. Of the 40 NSCLC publications identified in the review, 20 studies that used the ICC for cachexia or reported WL ≥ 5% and that performed multivariate analyses with hazard ratios (HRs) or Kaplan-Meier curves were included in the feasibility assessment. Of these, 16 studies (80%; n = 6225 patients; published 2016-2021) met the criteria for inclusion in the meta-analysis: 11 studies (69%) used the ICC and 5 studies (31%) used WL ≥ 5%. Combined criteria (ICC plus WL ≥ 5%) were associated with an 82% higher mortality risk versus no cachexia or WL < 5% (pooled HR [95% confidence interval, CI]: 1.82 [1.47, 2.25]). Although statistical heterogeneity was high (I = 88%), individual study HRs were directionally aligned with the pooled estimate, and there was considerable overlap in CIs across included studies. A subgroup analysis of studies using the ICC (HR [95% CI]: 2.26 [1.80, 2.83]) or WL ≥ 5% (HR [95% CI]: 1.28 [1.12, 1.46]) showed consistent findings. Assessments of methodological, clinical and statistical heterogeneity indicated that the meta-analysis was robust. Overall, this analysis found that ICC-defined cachexia or WL ≥ 5% was associated with inferior survival in patients with NSCLC. Routine assessment of both weight and weight changes in the oncology clinic may help identify patients with NSCLC at risk for worse survival, better inform clinical decision-making and assess eligibility for cachexia clinical trials.
PubMed: 38650388
DOI: 10.1002/jcsm.13477 -
Genome Research Apr 2024Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a...
Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a pathogenic variant, variant allele frequency (VAF), must reach a threshold before a biochemical defect occurs, termed the biochemical threshold. Whether the often-cited biochemical threshold of >60% VAF is similar across mtDNA variants and cell types is unclear. In our systematic review, we sought to identify the biochemical threshold of mtDNA variants in relation to VAF by human tissue/cell type. We used controlled vocabulary terms to identify articles measuring oxidative phosphorylation (OXPHOS) complex activities in relation to VAF. We identified 76 eligible publications, describing 69, 12, 16, and 49 cases for complexes I, III, IV, and V, respectively. Few studies evaluated OXPHOS activities in diverse tissue types, likely reflective of clinical access. A number of cases with similar VAFs for the same pathogenic variant had varying degrees of residual activity of the affected complex, alluding to the presence of modifying variants. Tissues and cells with VAFs <60% associated with low complex activities were described, suggesting the possibility of a biochemical threshold of <60%. Using Kendall rank correlation tests, the VAF of the m.8993T > G variant correlated with complex V activity in skeletal muscle (τ = -0.58, = 0.01, n = 13); however, no correlation was observed in fibroblasts ( = 0.7, n = 9). Our systematic review highlights the need to investigate the biochemical threshold over a wider range of VAFs in disease-relevant cell types to better define the biochemical threshold for specific mtDNA variants.
Topics: Humans; DNA, Mitochondrial; Gene Frequency; Genetic Variation; Mitochondria; Mitochondrial Diseases; Oxidative Phosphorylation
PubMed: 38627095
DOI: 10.1101/gr.278200.123 -
Journal of Sport and Health Science Apr 2024The benefits of exercise are well known; however, many of the underlying molecular mechanisms are not fully understood. Skeletal muscle secretes myokines, which mediate... (Review)
Review
BACKGROUND
The benefits of exercise are well known; however, many of the underlying molecular mechanisms are not fully understood. Skeletal muscle secretes myokines, which mediate muscle-organ crosstalk. Myokines regulate satellite-cell proliferation and migration, inflammatory cascade, insulin secretion, angiogenesis, fatty oxidation, and cancer suppression. To date, the effects of different exercise modes (namely, aerobic and resistance exercise) on myokine response remain to be elucidated. This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment.
METHODS
A systematic search was undertaken in PubMed, Medline, CINAHL, Embase, SPORTDiscus, and Web of Science in April 2023. Eligible studies examining the effects of a single bout of exercise on interleukin15 (IL-15), irisin, secreted protein acidic and rich in cysteine (SPARC), oncostatin M (OSM), and decorin were included. A random-effects meta-analysis was also undertaken to quantify the magnitude of change.
RESULTS
Sixty-two studies were included (n = 1193). Overall, exercise appeared to induce small to large increases in myokine expression, with effects observed immediately after to 60 min post-exercise, although these were mostly not statistically significant. Both aerobic and resistance exercise resulted in changes in myokine levels, without any significant difference between training modes, and with the magnitude of change differing across myokines. Myokine levels returned to baseline levels within 180 min to 24 h post-exercise. However, owing to potential sources of heterogeneity, most changes were not statistically significant, indicating that precise conclusions cannot be drawn.
CONCLUSION
Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation. Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response.
PubMed: 38604409
DOI: 10.1016/j.jshs.2024.04.005 -
The Archives of Bone and Joint Surgery 2024Brachial plexus injuries (BPI), although rare, often results in significant morbidity. Stem cell was thought to be one of BPI treatment modalities because of their... (Review)
Review
OBJECTIVES
Brachial plexus injuries (BPI), although rare, often results in significant morbidity. Stem cell was thought to be one of BPI treatment modalities because of their nerve-forming regeneration potential. Although there is a possibility for the use of mesenchymal stem cells as one of BPI treatment, it is still limited on animal studies. Therefore, this systematic review aimed to analyze the role of mesenchymal stem cells in nerve regeneration in animal models of brachial plexus injury.
METHOD
This study is a systematic review with PROSPERO registration number CRD4202128321. Literature searching was conducted using keywords experimental, animal, brachial plexus injury, mesenchymal stem cell implantation, clinical outcomes, electrophysiological outcomes, and histologic outcomes. Searches were performed in the PubMed, Scopus, and ScienceDirect databases. The risk of bias was assessed using SYRCLE's risk of bias tool for animal studies. The data obtained were described and in-depth analysis was performed.
RESULT
Four studies were included in this study involving 183 animals from different species those are rats and rabbits. There was an increase in muscle weight and shortened initial onset time of muscle contraction in the group treated with stem cells. Electrophysiological results showed that mesenchymal stem cells exhibited higher (Compound muscle action potential) CMAP amplitude and shorter CMAP latency than control but not better than autograft. Histological outcomes showed an increase in axon density, axon number, and the formation of connections between nerve cells and target muscles.
CONCLUSION
Mesenchymal stem cell implantation to animals with brachial plexus injury showed its ability to regenerate nerve cells as evidenced by clinical, electrophysiological, and histopathological results. However, this systematic study involved experimental animals from various species so that the results cannot be uniformed, and conclusion should be drawn cautiously.
PubMed: 38577510
DOI: 10.22038/ABJS.2024.68053.3224 -
Journal of Cachexia, Sarcopenia and... Jun 2024Low skeletal muscle mass (LSMM) and/or, function associated with an increased risk of treatment-related toxicities and inferior overall survival (OS) among adults with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Low skeletal muscle mass (LSMM) and/or, function associated with an increased risk of treatment-related toxicities and inferior overall survival (OS) among adults with solid malignancies. However, the association between LSMM and treatment-related toxicities among adults with haematologic malignancies remains unclear.
METHODS
Using a pre-published protocol (CRD42020197814), we searched seven bibliographic databases from inception to 08/2021 for studies reporting the impact of LSMM among adults ≥18 years with a known haematologic malignancy. The primary outcome of interest was OS, and secondary outcomes included progression free survival (PFS) and non-relapse mortality (NRM). These effect sizes were quantified in terms of hazards ratio (HR) along with 95% confidence interval (CI) and pooled across studies using a DerSimonian-Laird random-effects model. Heterogeneity was assessed using the Cochran's Q and the I statistic. All hypothesis testing was two-sided with an alpha of 0.05.
RESULTS
Of 3791 studies screened, we identified 20 studies involving 3468 patients with a mean age of 60 years; 44% were female and the most common malignancy was diffuse large B-cell lymphoma (42%). Most studies measured muscle mass using single slice computed tomography imaging at the L3 level. The presence of LSMM was associated with worse OS (pooled HR = 1.81, 95% CI = 1.48-2.22, P < 0.001) with moderate heterogeneity (Cochran's Q, I = 60.4%), PFS (pooled HR = 1.61, 95% CI = 1.28-2.02, P < 0.001) with moderate heterogeneity (Cochran's Q, I = 66.0%). Similarly, LSMM was associated with worse NRM (HR = 1.72, 95% CI = 1.34-2.22, P < 0.001) with little evidence of heterogeneity (Cochran's Q, I = 0.0%).
CONCLUSIONS
LSMM is associated with worse survival outcomes among adults with haematologic malignancies. Further research into understanding the underlying mechanism of this association and mitigating the negative effects of LSMM among adults with haematologic malignancies is needed.
Topics: Humans; Hematologic Neoplasms; Muscle, Skeletal; Treatment Outcome; Adult; Middle Aged; Female; Male
PubMed: 38558541
DOI: 10.1002/jcsm.13446 -
Journal of Research in Medical Sciences... 2023Human T-cell lymph tropic virus type 1 (HTLV-I)-related myelopathy/tropical spastic paraparesis (TSP) is a progressive inflammatory process affecting the spinal cord... (Review)
Review
Nonpharmacological interventions and outcomes in the management of complications of human T-cell lymphotropic virus type 1-related myelopathy/tropical spastic paraparesis: A systematic review.
BACKGROUND
Human T-cell lymph tropic virus type 1 (HTLV-I)-related myelopathy/tropical spastic paraparesis (TSP) is a progressive inflammatory process affecting the spinal cord that occurs as a result of HTLV 1. The use of nonpharmacological approaches has always been one of the treatment strategies in these patients, but disagreement about these interventions and their results has led to their limited use. Therefore, this study aimed to identify nonpharmacological interventions and their consequences in these patients.
MATERIALS AND METHODS
We followed the Cochrane Handbook for systematic reviews of interventions. The present report is organized according to the preferred reporting items for systematic reviews and meta-analyses. This study was conducted at PubMed, Cochrane Library, Web of Science, and Scopus, among all published studies by December 30, 2021. Keywords were: HTLV-1, Human T-lymph tropic virus 1, HTLV-I-associated myelopathy, HAM/TSP, tropical spastic paraparesis, nonpharmacological intervention, nonpharmacological treatment, massage, physiotherapy, acupuncture, acupressure, and exercise. The quality of the studies was assessed using JADAD.
RESULTS
Of 288 articles, 11 were eligible for data extraction published between 2014 and 2021. 90/9% of studies were randomized clinical trials. 81/8% of articles were of high quality. The total sample size was 253 people, of which 137 (54/15%) were women. Approaches such as exercise and motion therapy, electrotherapy, behavioral therapy, and virtual reality can be used for these patients. With these interventions, results such as improved mobility and balance, physical condition, pain, quality of life, muscle spasticity, maximum inspiratory pressure, and urinary symptoms can be achieved.
CONCLUSION
The most common physical therapy method used in studies was active and passive body movements, which are associated with positive results for patients. Due to the small sample size in this group of studies, it is necessary to conduct more clinical trials for more accurate conclusions. Furthermore, due to the limited number of studies that have used electrical stimulation or combined intervention packages, it is not possible to say with certainty what effect these methods have on patients. It is necessary to conduct more clinical trials.
PubMed: 38510783
DOI: 10.4103/jrms.jrms_300_22 -
Acta Biomaterialia Apr 2024While most of current models investigating bone remodelling are based on matrix deformation, intramedullary pressure also plays a role. Bone remodelling is orchestrated... (Review)
Review
While most of current models investigating bone remodelling are based on matrix deformation, intramedullary pressure also plays a role. Bone remodelling is orchestrated by the Lacuno-Canalicular Network (LCN) fluid-flow. The aim of this review was hence to assess the influence of intramedullary pressure on the fluid circulation within the LCN. Three databases (Science Direct, Web of Science, and PubMed) were used. The first phase of the search returned 731 articles, of which 9 respected the inclusion/exclusion criteria and were included. These studies confirm the association between intramedullary pressure and fluid dynamics in the LCN. Among the included studies, 7 experimental studies using animal models and 2 numerical models were found. The studies were then ranked according to the nature of the applied loading, either axial compression or direct cyclic intramedullary pressure. The current review revealed that there is an influence of intramedullary pressure on LCN fluid dynamics and that this influence depends on the magnitude and the frequency of the applied pressure. Two studies confirmed that the influence was effective even without bone matrix deformation. While intramedullary pressure is closely associated with LCN fluid, there is a severe lack of studies on this topic. STATEMENT OF SIGNIFICANCE: Since the 1990's, numerical models developed to investigate fluid flow in bone submicrometric porous network are based on the flow induced by matrix deformation. Bone fluid flow is known to be involved in cells stimulation and hence directly influences bone remodeling. Different studies have shown that intramedullary pressure is also associated with bone mechanosensitive adaptation. This pressure is developed in bone due to blood circulation and is increased during loading or muscle stimulation. The current article reviews the studies investigating the influence of this pressure on bone porous fluid flow. They show that fluid flow is involved by this pressure even without bone matrix deformation. The current review article highlights the severe lack of studies about this mechanism.
Topics: Animals; Bone and Bones; Bone Matrix; Bone Remodeling; Hydrodynamics; Models, Animal; Osteocytes
PubMed: 38484832
DOI: 10.1016/j.actbio.2024.03.003 -
European Journal of Medical Research Mar 2024Enterocystoplasty is the most commonly used treatment for bladder reconstruction. However, it has some major complications. In this study, we systematically reviewed the... (Review)
Review
Enterocystoplasty is the most commonly used treatment for bladder reconstruction. However, it has some major complications. In this study, we systematically reviewed the alternative techniques for enterocystoplasty using different scaffolds. A comprehensive search was conducted in PubMed, Embase, and Cochrane Library, and a total of 10 studies were included in this study. Five different scaffolds were evaluated, including small intestinal submucosa (SIS), biodegradable scaffolds seeded with autologous bladder muscle and urothelial cells, dura mater, human cadaveric bladder acellular matrix graft, and bovine pericardium. The overall results revealed that bladder reconstruction using regenerative medicine is an excellent alternative method to enterocystoplasty regarding the improvement of bladder capacity, bladder compliance, and maximum detrusor pressure; however, more large-scale studies are required.
Topics: Humans; Animals; Cattle; Regenerative Medicine; Urinary Bladder; Urologic Surgical Procedures; Muscles; Plastic Surgery Procedures
PubMed: 38475865
DOI: 10.1186/s40001-024-01757-z -
Dementia & Neuropsychologia 2024The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been... (Review)
Review
UNLABELLED
The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been well-researched in organs such as adipose tissue, muscle, and liver, has been linked to neurodegenerative diseases like Alzheimer's disease (AD) when it occurs in the brain.
OBJECTIVE
The authors aimed to gather data from the current literature on brain insulin resistance (BIR) and its likely repercussions on neurodegenerative disorders, more specifically AD, through a systematic review.
METHODS
A comprehensive search was conducted in multiple medical databases, including the Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline), and PubMed, employing the descriptors: "insulin resistance", "brain insulin resistance", "Alzheimer's disease", "neurodegeneration", and "cognition". The authors focused their search on English-language studies published between 2000 and 2023 that investigated the influence of BIR on neurodegenerative disorders or offered insights into BIR's underlying mechanisms. Seventeen studies that met the inclusion criteria were selected.
RESULTS
The results indicate that BIR is a phenomenon observed in a variety of neurodegenerative disorders, including AD. Studies suggest that impaired glucose utilization and uptake, reduced adenosine triphosphate (ATP) production, and synaptic plasticity changes caused by BIR are linked to cognitive problems. However, conflicting results were observed regarding the association between AD and BIR, with some studies suggesting no association.
CONCLUSION
Based on the evaluated studies, it can be concluded that the association between AD and BIR remains inconclusive, and additional research is needed to elucidate this relationship.
PubMed: 38425702
DOI: 10.1590/1980-5764-DN-2023-0032 -
Journal of Clinical Medicine Feb 2024Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor () gene on the long arm of the X chromosome. As a result...
Androgen Insensitivity Syndrome with Bilateral Gonadal Sertoli Cell Lesions, Sertoli-Leydig Cell Tumor, and Paratesticular Leiomyoma: A Case Report and First Systematic Literature Review.
Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor () gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient's gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli-Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient's karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations-a pathogenic frameshift deletion in the gene (c.77delT) and a likely pathogenic missense variant in the gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads ( = 225; age: 4-84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases ( = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2-49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS.
PubMed: 38398243
DOI: 10.3390/jcm13040929