General versus Neuraxial Anesthesia on Clinical Outcomes in Patients Receiving Hip Fracture Surgery: An Analysis of the ACS NSQIP Database.

Whether the use of neuraxial anesthesia or general anesthesia leads to more favorable postoperative outcomes in patients receiving hip fracture surgery remains unclear. We used data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Data Files between 2016 and 2020 to investigate the association of neuraxial anesthesia and general anesthesia with morbidity and mortality after hip fracture surgery. Inverse probability of treatment weighting (IPTW) was used to balance the baseline characteristics, and multivariable Cox regression models were used to estimate the hazard ratio (HR) with a 95% confidence interval (CI) for postoperative morbidity and mortality among the different anesthesia groups. A total of 45,874 patients were included in this study. Postoperative adverse events occurred in 1087 of 9864 patients (11.0%) who received neuraxial anesthesia and in 4635 of 36,010 patients (12.9%) who received general anesthesia. After adjustment for IPTW, the multivariable Cox regressions revealed that general anesthesia was associated with increased risks of postoperative morbidity (adjusted HR, 1.19; 95% CI, 1.14-1.24) and mortality (adjusted HR, 1.09; 95% CI, 1.03-1.16). The results of the present study suggest that, compared with general anesthesia, neuraxial anesthesia is associated with lower risks of postoperative adverse events in patients undergoing hip fracture surgery.

Preoperative renal insufficiency predicts postoperative adverse outcomes in a mixed surgical population: a retrospective matched cohort study using the NSQIP database.

BACKGROUND: The incidence of chronic kidney disease is increasing, but most cases are not diagnosed until the accidental finding of abnormal laboratory data or the presentation of severe symptoms. Patients with chronic kidney disease are reported to have an increased risk of postoperative mortality and morbidities, but previous studies mainly targeted populations undergoing cardiovascular surgery. The authors aimed to evaluate the risk of postoperative mortality and complications in a surgical population with preoperative renal insufficiency (RI). MATERIALS AND METHODS: This retrospective cohort study used data from the National Surgical Quality Improvement Program database between 2013 and 2018 to evaluate the risk of postoperative morbidity and mortality in the surgical population. Patients with estimated glomerular filtration rate less than 60 ml/min/1.73 m 2 were defined as the RI group. Propensity score matching methods and multivariate logistic regression were used to calculate the risk of postoperative morbidity and mortality. RESULTS: After propensity score matching, 502 281 patients were included in the RI and non-RI groups. The RI group had a higher risk of 30-day in-hospital mortality (odds ratio: 1.54, 95% CI: 1.49-1.58) than the non-RI group. The RI group was associated with a higher risk of postoperative complications, including myocardial infarction, stroke, pneumonia, septic shock, and postoperative bleeding. The RI group was also associated with an increased risk of prolonged ventilator use for over 48 h, readmission, and reoperation. CONCLUSION: Patients with preoperative RI have an increased risk of postoperative 30-day mortality and complications. RI group patients with current dialysis, estimated glomerular filtration rate less than or equal to 30 ml/min/1.73 m 2 or concomitant anemia had an elevated risk of postoperative mortality.

Effect of age on biomaterial-mediated in situ bone tissue regeneration.

Emerging studies show the potential application of synthetic biomaterials that are intrinsically osteoconductive and osteoinductive as bone grafts to treat critical bone defects. Here, the biomaterial not only assists recruitment of endogenous cells, but also supports cellular activities relevant to bone tissue formation and function. While such biomaterial-mediated in situ tissue engineering is highly attractive, success of such an approach relies largely on the regenerative potential of the recruited cells, which is anticipated to vary with age. In this study, we investigated the effect of the age of the host on mineralized biomaterial-mediated bone tissue repair using critical-sized cranial defects as a model system. Mice of varying ages, 1-month-old (juvenile), 2-month-old (young-adult), 6-month-old (middle-aged), and 14-month-old (elderly), were used as recipients. Our results show that the bio-mineralized scaffolds support bone tissue formation by recruiting endogenous cells for all groups albeit with differences in an age-related manner. Analyses of bone tissue formation after 2 and 8 weeks post-treatment show low mineral deposition and reduced number of osteocalcin and tartrate-resistant acid phosphatase (TRAP)-expressing cells in elderly mice. STATEMENT OF SIGNIFICANCE: Tissue engineering strategies that promote tissue repair through recruitment of endogenous cells will have a significant impact in regenerative medicine. Previous studies from our group have shown that biomineralized materials containing calcium phosphate minerals can contribute to neo-bone tissue through recruitment and activation of endogenous cells. In this study, we investigated the effect of age of the recipient on biomaterial-mediated bone tissue repair. Our results show that the age of the recipient mouse had a significant impact on the quality and quantity of the engineered neo-bone tissues, in which delayed/compromised bone tissue formation was observed in older mice. These findings are in agreement with the clinical observations that age of patients is a key factor in bone repair.

WNT3A promotes myogenesis of human embryonic stem cells and enhances in vivo engraftment.

The ability of human embryonic stem cells (hESCs) to differentiate into skeletal muscle cells is an important criterion in using them as a cell source to ameliorate skeletal muscle impairments. However, differentiation of hESCs into skeletal muscle cells still remains a challenge, often requiring introduction of transgenes. Here, we describe the use of WNT3A protein to promote in vitro myogenic commitment of hESC-derived cells and their subsequent in vivo function. Our findings show that the presence of WNT3A in culture medium significantly promotes myogenic commitment of hESC-derived progenitors expressing a mesodermal marker, platelet-derived growth factor receptor-α (PDGFRA), as evident from the expression of myogenic markers, including DES, MYOG, MYH1, and MF20. In vivo transplantation of these committed cells into cardiotoxin-injured skeletal muscles of NOD/SCID mice reveals survival and engraftment of the donor cells. The cells contributed to the regeneration of damaged muscle fibers and the satellite cell compartment. In lieu of the limited cell source for treating skeletal muscle defects, the hESC-derived PDGFRA(+) cells exhibit significant in vitro expansion while maintaining their myogenic potential. The results described in this study provide a proof-of-principle that myogenic progenitor cells with in vivo engraftment potential can be derived from hESCs without genetic manipulation.

Adjunctive traditional Chinese medicine therapy improves survival in patients with advanced breast cancer: a population-based study.

BACKGROUND: Traditional Chinese medicine (TCM) is one of the most common complementary and alternative medicines used in the treatment of patients with breast cancer. However, the clinical effect of TCM on survival, which is a major concern in these individuals, lacks evidence from large-scale clinical studies. METHODS: The authors used the Taiwan National Health Insurance Research Database to conduct a retrospective population-based cohort study of patients with advanced breast cancer between 2001 and 2010. The patients were separated into TCM users and nonusers, and Cox regression models were applied to determine the association between the use of TCM and patient survival. RESULTS: A total of 729 patients with advanced breast cancer receiving taxanes were included in the current study. Of this cohort, the mean age was 52.0 years; 115 patients were TCM users (15.8%) and 614 patients were TCM nonusers. The mean follow-up was 2.8 years, with 277 deaths reported to occur during the 10-year period. Multivariate analysis demonstrated that, compared with nonusers, the use of TCM was associated with a significantly decreased risk of all-cause mortality (adjusted hazards ratio [HR], 0.55 [95% confidence interval, 0.33-0.90] for TCM use of 30-180 days; adjusted HR, 0.46 [95% confidence interval, 0.27-0.78] for TCM use of >180 days). Among the frequently used TCMs, those found to be most effective (lowest HRs) in reducing mortality were Bai Hua She She Cao, Ban Zhi Lian, and Huang Qi. CONCLUSIONS: The results of the current observational study suggest that adjunctive TCM therapy may lower the risk of death in patients with advanced breast cancer. Future randomized controlled trials are required to validate these findings.

Human mesenchymal stem cells suppress the stretch-induced inflammatory miR-155 and cytokines in bronchial epithelial cells.

Current research in pulmonary pathology has focused on inflammatory reactions initiated by immunological responses to allergens and irritants. In addition to these biochemical stimuli, physical forces also play an important role in regulating the structure, function, and metabolism of the lung. Hyperstretch of lung tissues can contribute to the inflammatory responses in asthma, but the mechanisms of mechanically induced inflammation in the lung remain unclear. Our results demonstrate that excessive stretch increased the secretion of inflammatory cytokines by human bronchial epithelial cells (hBECs), including IL-8. This increase of IL-8 secretion was due to an elevated microRNA-155 (miR-155) expression, which caused the suppression of Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) production and the subsequent activation of JNK signaling. In vivo studies in our asthmatic mouse model also showed such changes in miR-155, IL-8, and SHIP1 expressions that reflect inflammatory responses. Co-culture with human mesenchymal stem cells (hMSCs) reversed the stretch-induced hBEC inflammatory responses as a result of IL-10 secretion by hMSCs to down-regulate miR-155 expression in hBECs. In summary, we have demonstrated that mechanical stretch modulates the homeostasis of the hBEC secretome involving miR-155 and that hMSCs can be used as a potential therapeutic approach to reverse bronchial epithelial inflammation in asthma.

Internalization is essential for the antiapoptotic effects of exogenous thymosin beta-4 on human corneal epithelial cells.

PURPOSE: Exogenous thymosin beta-4 (Tbeta(4)) has been shown to inhibit the apoptosis in nontransformed human corneal epithelial cells that is triggered by ethanol. The purpose of this study is to examine whether exogenous Tbeta(4) protects SV40-immortalized human corneal epithelial T (HCE-T) cells against the toxic effects of Fas ligand (FasL) and hydrogen peroxide (H(2)O(2)) and to elucidate its mechanism of action. METHODS: HCE-T cells were incubated without or with the recombinant histidine-tagged Tbeta(4) produced by Escherichia coli before the addition of FasL or H(2)O(2). Cell viability was determined by MTT or MTS assay, and activation of caspase-8, -9, and -3 was examined by colorimetric and fluorescent substrate cleavage assays. The internalization of exogenous Tbeta(4) in HCE-T cells was analyzed by immunofluorescence staining. Cytochalasin D, an actin depolymerization agent, was added to examine whether the actin cytoskeleton is involved in Tbeta(4) entry and whether the internalization of this peptide is crucial for its cytoprotection. RESULTS: The death of HCE-T cells induced by both FasL and H(2)O(2) was dramatically reduced by the recombinant Tbeta(4) pretreatment. Moreover, FasL-mediated activation of caspases-8 and -3 as well as H(2)O(2)-triggered stimulation of caspases-9 and -3 in these cells was abolished by preincubating them with the exogenous Tbeta(4). Of note, internalization of this G-actin-sequestering peptide into HCE-T cells was found to be essential in cell death prevention, in that disruption of the cellular entry of Tbeta(4) by cytochalasin D abrogated its cytoprotective effects. CONCLUSIONS: This is the first report to demonstrate that the internalization of exogenous Tbeta(4) is essential for its antiapoptotic activity in human corneal epithelial cells.