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BACKGROUND: Several studies have found that the prognostic nutritional index (PNI), controlling nutritional status (CONUT), and Glasgow Prognostic Score (GPS) of patients with laryngeal cancer accurately predict their prognosis. However, there is no consensus regarding the best assessment tool. Therefore, this study aimed to confirm the predictive value of the three nutritional scoring systems for the prognosis of patients with laryngeal cancer. METHODS: This study analyzed a cohort of 427 patients with laryngeal cancer who visited our hospital. PNI, CONUT, and GPS were calculated, and the relationship between these indicators and prognosis was examined. RESULTS: The optimal cut-off levels for overall survival (OS) of laryngeal cancer patients determined by PNI, CONUT, and GPS were 45, 3, and 0, respectively. When patients were stratified based on these thresholds, OS and disease-free survival (DFS) were significantly decreased in the malnutrition group (all three, p < 0.05). The OS rates of patients with laryngeal cancer were significantly affected by the three scores according to multivariate analysis. CONCLUSIONS: The three scoring methods had a high predictive value for the prognosis of patients with laryngeal cancer, with GPS having the strongest correlation with the prognosis of laryngeal cancer patients.

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BACKGROUND: The number of trials investigating mesenchymal stromal cells (MSCs) soars within 3 years which urges a study analysing emerging MSC treatment-related adverse events. AIM: To assess the safety of MSC therapy and provide solid evidence for clinical translation of MSC. METHODS: A meta-analysis of randomized clinical trials (RCTs) published up to April 20th, 2023 was performed. Odds ratio (OR) and 95% confidential intervals (CIs) were used to display pooled results. RESULTS: 152 randomized clinical trials (RCTs) that incorporated 9228 individuals treated with MSCs from autologous or allogenic adipose tissue, bone marrow, Wharton's Jelly, and placenta tissue were included in the analysis. We discovered appropriate 21 MSC treatment-related adverse events (TRAEs), of which fever [OR, 1.61, 95% CI: 1.22-2.11, p<0.01] was the sole event that was closely associated with MSC therapy. MSCs also trended to lower the incidence rate of tachycardia [OR, 0.83, 95% CI: 0.64-1.09, p=0.14] and fatigue [OR, 0.18, 95% CI: 0.61-1.07, p=0.18]. A separate analysis of studies with long-term follow-up (more than 1 year) demonstrated the close relationship between MSCs and fever [OR, 1.75, 95% CI: 1.26-2.24, p<0.01]. The rest TRAEs did not associate themselves with MSC therapy. Dose-response was also conducted for fever, linearity was discovered between MSCs from allogeneic tissue and Wharton's Jelly and fever. CONCLUSION: To date, our results suggest that fever is the only AE closely associated with MSCs.

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Objective: Accurate cachexia staging is the key to its management. However, there is currently a lack of tools to distinguish the staging of cachexia in patients with cancer undergoing radiotherapy. The Radiotherapy Cachexia Staging Scale (R-CSS) was developed for the stratification of cachexia in patients undergoing cancer radiotherapy. Methods: Patients with cancer undergoing radiotherapy were divided into four stages - noncachexia, precachexia, cachexia, and refractory cachexia - by the R-CSS scale, and the clinical outcomes of the four groups were compared. Results: A total of 270 patients with cancer undergoing radiation therapy were included in the study. All participants were classified into four stages of cachexia: stage 0, I, II, and III. Patients with a higher cachexia stage had a higher prevalence of sarcopenia (P â€‹= â€‹0.015). Scores on the 16-item M. D. Anderson Symptom Inventory were higher in patients with higher cachexia stages (P â€‹< â€‹0.05), but levels of forgetfulness, numbness, and shortness of breath were not higher in these patients (P â€‹> â€‹0.05). Patients with higher cachexia stages exhibited better scores on the QLQ-C30 scale (P â€‹< â€‹0.05), except for in the domains of cognitive functioning, diarrhea, and dyspnea (P â€‹> â€‹0.05). The incidence of treatment-related events (any grade III or higher grade of [non-]hematologic adverse events, the need for hospitalization, emergency room admission) was higher in patients with higher cachexia stages. Conclusions: The R-CSS scale is a screening tool that can simultaneously distinguish different stages of cachexia.

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miRNA therapy is popularly investigated in treating acute spinal cord injury (SCI) and offers a significant prospect for the treatment of acute SCI. We aimed to provide pre-clinical validations of miRNA in the treatment of SCI. A systematic search of EMBASE, PubMed, Web of Science, the Cochrane Library, and Scopus databases was performed. Rats, which were the most used animals (70%, n = 46 articles), receiving miRNA therapy got prominent recovery in SCI models [BBB score, SMD 3.90, 95% CI 3.08-4.73, p < 0.01]. Locomotor function of fore and hind limbs in SCI mice receiving miRNA therapy (30%, n = 19 articles) [grip strength, SMD 3.22, 95% CI 2.14-4.26; p < 0.01; BBB score, SMD 3.47, 95% CI 2.38-4.56, p < 0.01; BMS, SMD 2.27, 95% CI 1.34-3.20, p < 0.01] also recovered better than mice in control group. Then, we conducted the subgroup analysis and did find that high-quality articles trended to report non-therapeutic effect of miRNA. Furtherly, we analyzed 46 miRNAs, including 9 miRNA families (miR-21-5p/34a-3p/124-3p/126-3p/223-3p/543-3p/30-3p/136-3p/15-5p), among which miR-30-3p/136-3p/15-5p family were not effective in recovering locomotor function of rats. Conclusively, miRNAs are curative drugs for SCI, however, appropriate miRNA carrier and which miRNA is the most efficacious for SCI should be furtherly investigated.

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BACKGROND: Novel scaffolds and stem cells are alternatives for the treatment of spinal cord injury (SCI), which causes life-long disability. However, there is a lack of synthesized evidence comparing different therapies. AIM: To examine the efficacy of various treatments in achieving locomotor recovery in SCI animals. The PubMed, Scopus and Web of Science databases were searched from inception to 21st May 2021. METHODS: The data were extracted by one investigator under the surveillance of a referee according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement and stored in Microsoft Excel. All data were analysed using Bayesian network analysis with a consistency model. The selection was performed in strict accordance with the participant, intervention, comparison, outcome and study (PICOS) principle, as specifically stated in the methods section. RESULTS: A total of 387 eligible studies involving 11169 animals subjected to 5 different treatments were evaluated. Compared to placebo or no treatment, scaffolds (mean difference (MD), 2.04; 95% credible interval (CrI): 1.58 to 2.50), exosomes (MD, 3.46; 95% CrI: 3.07 to 3.86), stem cells (MD, 4.18; 95% CrI: 3.28 to 5.07), scaffolds in conjunction with stem cells (MD, 5.26; 95% CrI: 4.62 to 5.89), and scaffolds in conjunction with non-cell agents (MD, 4.88; 95% CrI: 4.21 to 5.54) led to significant recovery of locomotor function in SCI animals. No significant difference in the locomotor function score was observed between animals treated with stem cells and those treated with exosomes (MD, 0.71; 95% CrI: -0.25 to 3.05), between animals treated with scaffolds in conjunction with stem cells and those treated with scaffolds in conjunction with non-cell agents (MD, -0.38; 95% CrI: -1.24 to 0.49), or between animals treated with scaffolds in conjunction with non-cell agents and those treated with stem cells (MD, 0.71; 95% CrI: - 0.38 to 1.80). CONCLUSION: Significant differences in the efficacy of various therapies in SCI animals were observed, and transplantation of scaffolds in conjunction with non-cell agents, scaffolds in conjunction with stem cells, and stem cells should be considered over transplantation of exosomes or scaffolds alone. Even though transplantation of scaffolds alone promoted locomotor function recovery in SCI animals, its use should be discouraged.

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STUDY DESIGN: A meta-analysis of early surgery for acute thoracolumbar spinal cord injury. OBJECTIVE: To evaluate whether early surgery increases the American Spinal Injury Association (ASIA) grade of patients confronted with acute thoracolumbar spinal cord injury. SUMMARY OF BACKGROUND DATA: The idea that early surgery aids the recovery of spinal cord function in patients confronted with acute thoracolumbar spinal cord injury is controversial. METHODS: All articles were retrieved from the PubMed, Embase, Web of Science and Scopus databases, which were searched from onset until 1 May 2021. All data are presented as odds ratios (ORs) and mean deviations (MDs) with 95% confidential intervals (CIs). RESULTS: Ten studies, including 6 prospective studies, 3 retrospective studies, and 1 randomized controlled trial, containing 952 patients, were included in the analysis. The results showed that early surgery significantly reduced the number of patients with ASIA grade A (OR 0.27, 95% CI: 0.13-0.58, P <0.01) and B (OR 0.56, 95% CI: 0.39-0.82, P <0.01) status but greatly increased the number of patients with grade E status (OR 1.44, 95% CI: 1.06-1.96, P <0.01). Generally, the patients receiving early surgery achieved >1 ASIA grade improvement (OR 1.70, 95% CI: 1.31-2.21, P <0.01) or >2 ASIA grade (OR 3.55, 95% CI: 2.20-5.70, P <0.01) improvements. Although early surgery did not reduce the incidence of operative complications (OR 0.72, 95% CI: 0.45-1.16, P <0.01), the duration of hospitalization was greatly shortened (MD-3.48, 95% CI: -0.45 to-2.91, P <0.01). CONCLUSIONS: The spinal cord function of acute thoracolumbar spinal cord injury patients can benefit from early decompression. This conclusion should be further verified with randomized controlled trials.

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Even though reunion of bone fracture confronts clinicians, mesenchymal stromal cells (MSCs) are investigated to be curative in bone fracture. This study aimed to explore the application potential of MSCs for healing bone fractures. By inputting search terms and retrieving studies published up to March 2021, multiple databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, were searched to identify eligible studies. The mean difference (MD) and 95% confidence interval (95% CI) were calculated to analyze the main results in the meta-analysis. Data analysis was performed using Engauge Digitizer 10.8 and R Software. Of the 31 articles, 26 were preclinical studies (n = 913), and 5 were clinical trials (n = 335). Preclinically, MSCs therapy significantly augmented the progress of bone regeneration [(bone volume over tissue volume (MD7.35, p < 0.01)], despite some non-significant effects (on the callus index, bone strength, work to failure, and stiffness). Clinically, the MSC group had a significantly reduced incidence of poor recovery (odds ratio (OR) 0.30, p < 0.01); however, a significant decrease in healing time was not observed in the MSC group (MD 2.47, p = 0.26). In summary, our data suggest that patients with bone fractures benefited from MSC administration and that MSCs are a potentially useful agent for bone regeneration. Despite these satisfactory outcomes, larger randomised clinical trials (RCTs) are necessary to confirm these findings.

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BACKGROUND: Benefiting from in-depth research into stem cells, extracellular vesicles (EVs), which are byproducts of cells and membrane-wrapped microvesicles (30-120 nm) containing lipids, proteins, and nucleic acids, may cast light on the research and development of therapeutics capable of improving the neurological recovery of spinal cord injury (SCI) animals. However, the mechanistic modes of action for EVs in alleviating the lesion size of SCI remain to be solved, thus presenting a tremendous gap existing in translation from the laboratory to the clinic. OBJECTIVE: The purpose of this minireview was to cover a wide range of basic views on EVs involved in SCI treatment, including the effects of EVs on the pathogenesis, treatment, and diagnosis of spinal cord injury. METHODS: We searched databases (i.e., PubMed, Web of Science, Scopus, Medline, and EMBASE) and acquired all accessible articles published in the English language within five years. Studies reporting laboratory applications of EVs in the treatment of SCI were included and screened to include studies presenting relevant molecular mechanisms. RESULTS: This review first summarized the basic role of EVs in cell communication, cell death, inflammatory cascades, scar formation, neuronal regrowth, and angiogenesis after SCI, thereby providing insights into neuroprotection and consolidated theories for future clinical application of EVs. CONCLUSION: EVs participate in an extremely wide range of cell activities, play a critical role in cell communication centring neurons, and are considered potential therapies and biomarkers for SCI. miRNAs are the most abundant nucleic acids shipped by EVs and effluent cytokines, and they may represent important messengers of EVs and important factors in SCI treatment.

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BACKGROUND: Despite increasing clinical investigations emphasizing the safety of mesenchymal stem cell (MSC) therapy in different populations with different diseases, no article has recently reviewed the adverse events in all populations. AIM: To evaluate the safety of MSC therapy in all populations receiving MSC therapy and explore the potential heterogeneities influencing the clinical application of MSCs. METHODS: The PubMed, Embase, Web of Science and Scopus databases were searched from onset until 1 March 2021. RESULTS: All adverse events are displayed as odds ratios (ORs) and 95% CIs (confidential intervals). In total, 62 randomized clinical trials were included that enrolled 3546 participants diagnosed with various diseases (approximately 20 types of diseases) treated with intravenous or local implantation versus placebo or no treatment. All studies were of high quality, and neither serious publication bias nor serious adverse events (such as death and infection) were discovered across the included studies. The pooled analysis demonstrated that MSC administration was closely associated with transient fever (OR, 3.65, 95% CI 2.05-6.49, p < 0.01), administration site adverse events (OR, 1.98, 95% CI 1.01-3.87, p = 0.05), constipation (OR, 2.45, 95% CI 1.01-5.97, p = 0.05), fatigue (OR, 2.99, 95% CI 1.06-8.44, p = 0.04) and sleeplessness (OR, 5.90, 95% CI 1.04-33.47, p = 0.05). Interestingly, MSC administration trended towards lowering rather than boosting the incidence rate of arrhythmia (OR, 0.62, 95% CI 0.36-1.07, p = 0.09). CONCLUSIONS: Conclusively, MSC administration was safe in different populations compared with other placebo modalities.

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CONTEXT: There are no recommended therapeutic agents for acute spinal cord injury (SCI) due to the pathophysiological complexity of the injury. OBJECTIVE: The objective of this study is to investigate the efficacy of various exosomes and potential factors impacting the efficacy of exosomes. METHODS: We searched the PubMed, EMBASE, Web of Science, Medline, Scopus, and Cochrane Library databases to systematically collect articles comparing the locomotor function of SCI rodents undergoing exosome treatment and untreated SCI rodents. No language was preferred. RESULTS: Pooled analysis revealed that the locomotor function recovery of SCI rodents receiving exosomes was greatly improved (583 rats, 3.12, 95% CI: 2.56-3.67, p < 0.01; 116 mice, 2.46, 95% CI: 1.20-3.72, p < 0.01) compared to those of control rodents. The trial sequential analysis demonstrated the findings of the meta-analysis with the cumulative Z-curve crossing the upper monitoring boundary for the benefit and reaching the adjusted required information size. However, the origin of the exosome, SCI model, and administration method determined the therapeutic effect to some extent. CONCLUSIONS: Despite the proven therapeutic effects of exosomes on SCI rodents, the results should be interpreted cautiously considering the diversity in vivo and in vitro in relation to future trials.

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BACKGROUND: Clinically, severe burns remain one of the most challenging issues, but an ideal treatment is yet absent. Our purpose is to compare the efficacy of stem cell therapy in a preclinical model of burn wound healing. METHODS: Research reports on mesenchymal stem cells (MSCs) for burn wound healing were retrieved from 5 databases: PubMed, Embase, MEDLINE, Web of Science, and the Cochrane Library. The primary outcomes reported in this article include the un-healing rate of the wound area, the closure rate, and the wound area. Secondary outcomes included CD-31, vascular density, interleukin (IL)-10, thickness of eschar tissue, vascular endothelial growth factor (VEGF), and white blood cell count. Finally, a subgroup analysis was conducted to explore heterogeneity that potentially impacted the primary outcomes. A fixed-effects model with a 95% confidence interval (CI) was performed when no significant heterogeneity existed. Otherwise, a random-effects model was used. All data analysis was conducted by using Engauge Digitizer 10.8 and R software. RESULTS: Twenty eligible articles were finally included in the analysis. Stem cell therapy greatly improved the closure rate (2.00, 95% CI 0.52 to 3.48, p = 0.008) and compromised the wound area (- 2.36; 95% CI - 4.90 to 0.18; p = 0.069) rather than the un-healing rate of the wound area (- 11.10, 95% CI - 32.97 to 10.78, p = 0.320). Though p was 0.069, there was a trend toward shrinkage of the burn wound area after stem cell therapy. Vascular density (4.69; 95% CI 0.06 to 9.31; p = 0.047) and thickness of eschar tissue (6.56, 95% CI 1.15 to 11.98, p = 0.017) were also discovered to be significantly improved in the burn site of stem cell-treated animals. Moreover, we observed that animals in the stem cell group had an increased white blood cell count (0.84, 95% CI 0.01 to 1.66, p = 0.047) 5 days post treatment. Other indicators, such as VEGF (p = 0.381), CD-31 (p = 0.335) and IL-10 (p = 0.567), were not significantly impacted. CONCLUSIONS: Despite limited data from preclinical trials, this meta-analysis suggests that stem cell therapy is curative in decreasing the burn wound area and provides some insights into future clinical studies of stem cell therapy for burns.

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