Association of preoperative frailty with the risk of postoperative delirium in older patients undergoing hip fracture surgery: a prospective cohort study.

OBJECTIVE: This study aimed to explore the correlation between preoperative frailty and the risk of postoperative delirium (POD) in older patients undergoing hip fracture surgery. METHODS: In total, 148 patients with hip fractures who were admitted to Tsinghua Changgung Hospital (Beijing, China) between January 2022 and January 2023 were involved in this study. Preoperative frailty scales were assessed, of which the CAM scale was postoperatively administered every morning and evening on days 1, 2, 3, 5, and 7. Binary logistic regression analysis was conducted to determine the correlation between preoperative frailty and the risk of POD. RESULTS: Among 148 older patients with hip fractures, 71 (48.0%) were identified as preoperative frail and 77 (52.0%) as non-frail. The overall incidence of POD on day 7 was 24.3% (36/148), and preoperative frailty was associated with a significantly higher risk of POD compared with non-frailty (42.3% vs. 7.8%, P < 0.001). The binary logistic regression analysis revealed that preoperative frailty was noted as an independent risk factor for the risk of POD in older patients undergoing hip fracture surgery (P = 0.002). CONCLUSION: Preoperative frailty increased the risk of POD in older patients undergoing hip fracture surgery. DISCUSSION: Preoperative assessment of frailty in geriatric hip surgery can timely identify potential risks and provide interventions targeting frailty factors to reduce the incidence of POD in older patients undergoing hip fracture surgery. The findings suggested that preoperative frailty could increase the risk of POD in older patients undergoing hip fracture surgery. Further research is necessary to determine whether perioperative interventions aimed at enhancing frailty can mitigate the risk of POD and improve prognosis in older patients undergoing hip fracture surgery.

The impact of MIF deficiency on alterations of fecal microbiota in C57BL/6 mice induced by Trichinella spiralis infection.

Trichinellosis caused by Trichinella spiralis (T. spiralis) is a major food-borne parasitic zoonosis worldwide. Prevention of trichinellosis is an effective strategy to improve patient quality of life. Macrophage migration inhibitory factor (MIF) is closely related to the occurrence and development of several parasitic diseases. Studying the impact of MIF deficiency (Mif-/- ) on the alterations in host fecal microbiota due to T. spiralis infection may contribute to proposing a novel dual therapeutic approach for trichinellosis. To reveal the diversity and differences in fecal microbial composition, feces were collected from T. spiralis-uninfected and T. spiralis-infected wild-type (WT) and MIF knockout (KO) C57BL/6 mice at 0, 7, 14, and 35 days post-infection (dpi), and the samples were sent for 16S rRNA amplicon sequencing on the Illumina NovaSeq platform. Flow cytometry was used to determine the expression levels of IFN-γ and IL-4 in the CD4+ /CD8+ T-cell sets of mouse spleens. The results showed that operational taxonomic unit (OTU) clustering, relative abundance of microbial composition, alpha diversity, and beta diversity exhibited significant changes among the eight groups. The LEfSe analysis selected several potential biomarkers at the genus or species level, including Akkermansia muciniphila, Lactobacillus murinus, Coprococcus catus, Firmicutes bacterium M10_2, Parabacteroides sp. CT06, and Bacteroides between the KTs and WTs groups. The predicted bacterial functions of the fecal microbiota were mainly involved in metabolism, such as the metabolism of carbohydrates, amino acids, energy, cofactors, vitamins, nucleotides, glycans, and lipids. Flow cytometry revealed an increased CD3+ CD8- /CD3+ CD8+ T-cell ratio and increased IFN-γ and IL-4 levels in CD3+ CD8- T-cell sets from WT and MIF KO mice at 7 dpi. The results indicated that both MIF KO and infection time have a significant influence on the CD3+ CD8- IFN-γ+ and CD3+ CD8- IL-4+ response in mice after T. spiralis. In conclusion, this research showed alterations of the fecal microbiota and immune response in both WT and MIF KO mice before and after T. spiralis infection. These results revealed a potential role of MIF in regulating the pathogenesis of trichinellosis related to the intestinal microbiota. Importantly, the selected potential biomarkers combined with MIF will also offer a novel therapeutic approach to treat trichinellosis in the future.

Dexmedetomidine treatment prevents cerebral ischemic reperfusion injury through HIF-1α/Beclin1-mediated autophagy.

OBJECTIVE: Cerebral ischemic reperfusion injury (CIRI) is a common cerebrovascular disorder with high disability and morbidity that threatens human health. Former investigations found that dexmedetomidine (DEX) has a protective effect against CIRI, but regulatory mechanism is unclear. METHODS: The current study utilized C57BL/6 mice to establish a focal cerebral ischemic reperfusion model. Cerebral infarct volume was defined by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. BV2 cells and primary neurons were utilized for molecular mechanism studies after treatment with DEX or autophagy inhibitor 3-Methyladenine (3-Ma). RESULTS: Data revealed that DEX pretreatment protected nerves against CIRI. In vitro studies also found that DEX pretreatment enhanced microglial M2 polarization and protected against neuronal apoptosis by autophagy activation. Downregulation of hypoxia inducible factor (HIF)-1α or Beclin-1 inhibited the promotional effects of DEX on microglial M2 polarization and inhibited the protective effects of DEX against neuronal apoptosis. CONCLUSION: The present study found that DEX treatment protects against CIRI by modulating microglial polarization via HIF-1α/Beclin1-mediated autophagy.

A prediction model for difficult intubation using skeletal features in patients affected by apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) has been linked to increased risk of perioperative morbidity and mortality because of difficult intubation (DI). However, there is a lack of clinically validated tools to identify OSAHS patients who are likely to have an increased the risk of DI. METHODS: For model development, a prospective cohort study included patients with OSAHS who underwent elective surgery between September 2018 to December 2020. The outcome was DI and classified according to the Cormack-Lehane grading. Conventional airway assessment tests, skeletal features, and the severity of OSAHS were recorded, and LASSO regression was used. Validation was performed on an external sample of patients from the same hospital between January 2021 and December 2021. RESULTS: The development (prevalence of DI: 44%) and validation cohorts (prevalence of DI: 32%) included 247 and 82 patients, respectively. Based on the result of LASSO, age and four skeletal features (thyromental height, maximum mandibular protrusion, mandibulohyoid distance, and neck hypokinesis grade) were included in the final model. Discrimination and calibration of the model were satisfactory with high AUC (0.97), sensitivity (88.5%), specificity (94.6%), accuracy (92.7%), PPV (88.5%) and NPV (94.6%) from external validation. CONCLUSIONS: Our study developed and externally validated a DI prediction model using skeletal features in OSAHS patients. The final model had an NPV of nearly 95%, suggesting that a simple nomogram including only five predictors was quite helpful for ruling out the presence of difficult intubation in OSAHS patients who underwent elective surgery.

Deficiency of migration inhibitory factor influences the gut microbiota of C57BL/6 mice infected with Plasmodium berghei ANKA.

Cerebral malaria (CM), as one of the most common complications in severe malaria, has threatened millions of individuals' neurological health and even their lives. Macrophage migration inhibitory factor (MIF), a pleiotropic proinflammatory factor in humans, seems to be a risk factor for death in patients with CM, but its functional mechanism remains unclear. To verify whether affecting the intestinal microbes of the host was one of the mechanisms by which MIF regulates CM, C57BL/6 mice, including WT + PbA, MIF-KO + PbA and their uninfected controls, were sent for 16S rRNA-based sequencing targeting the V4 region of the intestinal microbiota through the Illumina MiSeq platform. The results showed that OTU clustering, alpha and beta diversity in the four groups involved had evident variation. The relative abundance at different taxonomic levels, especially the dominant intestinal flora, was obviously changed. The LEfSe analysis screened out several biomarkers, including significantly reduced Ligilactobacillus (Lactobacillus murinus) in WPbA mice compared to the WT group and Akkermansia (Akkermansia_muciniphila) in KPbA mice compared to the WPbA group. For MIF KO groups, mice infected with PbA or uninfected showed significant enrichment of producers of short-chain fatty acids, including Dubosiella and Faecalibaculum (Faecalibaculum rodentium) in KPbA, and Lachnospiraceae_NK4A136_group and Firmicutes_bacterium_M10-2 in KO. This study not only further proved the gut microbiota changes in C57BL/6 mice caused by PbA infection, but also found that MIF deletion directly affected the changes in the gut microbiota of C57BL/6 mice before and after PbA infection. This finding reveals a potential mechanism by which MIF regulates CM. Combining MIF with potential microbial biomarkers will provide a promising idea to develop combined drugs for improving CM in the future.

Risk factors for moderate-to-severe postoperative pain after percutaneous nephrolithotomy: a retrospective cohort study.

Percutaneous nephrolithotomy (PCNL) is a minimally invasive procedure for removing renal calculi, while a large number of patients experience acute moderate-to-severe pain despite the analgesia provided. This study aimed to explore the risk factors for postoperative pain after PCNL, which may provide a novel perspective to refine the enhanced recovery after surgery (ERAS) program and to improve clinical outcomes. The clinical data of 331 patients who underwent PCNL in our hospital from September 2020 to February 2021 were retrospectively analyzed. The pain intensity was assessed every 4 h until 24 h post-surgery. According to the visual analog scale (VAS) score, patients were divided into two groups: mild or no pain group (VAS score, 0-3) and moderate-to-severe pain group (VAS score, 4-10). The pre-, peri-, and post-operative data were collected and analyzed. The indicators with statistically significant differences were selected, and multivariate logistic regression analysis was employed to determine the risk factors for postoperative pain after PCNL. Among 331 patients, 221 patients had moderate-to-severe pain and the incidence rate was 66.77%. Multivariate logistic regression analysis showed that the independent risk factors for moderate-to-severe pain after PCNL were the diameter of the renal calculus (odds ratio (OR) = 6.23, 95% confidence interval (CI) 2.50-15.56, P = 0.001), the number of renal calculi (OR = 15.892, 95% CI 7.721-32.711, P < 0.01), the presence of residual calculi (OR = 1.780, 95% CI 0.897-3.533, P = 0.01), and operation time (OR = 1.033, 95% CI 1.020-1.046, P < 0.01). The diameter of the renal calculus, the number of renal calculi, the presence of residual calculi, and operation time were significant predictors of postoperative pain after PCNL.

Impact of changes in head position during head and neck surgery on the depth of tracheal tube intubation in anesthetized children.

BACKGROUND: The classic formula has been used to estimate the depth of tracheal tube intubation in children for decades. However, it is unclear whether this formula is applicable when the head and neck position changes intraoperatively. METHODS: We prospectively reviewed the data of 172 well-developed children aged 2-12 years (64.0% boys) who underwent head and neck surgery under general anesthesia. The distances from the tracheal carina to the endotracheal tube tip (CT), from the superior margin of the endotracheal tube tip to the vocal cord posterior commissure (CV), and from the tracheal carina to the posterior vocal commissure (TV) were measured in the sniffing position (maximum), neutral head, and maximal head flexion positions. RESULTS: Average CT and CV in the neutral head position were 4.33 cm and 10.4 cm, respectively. They increased to 5.43 cm and 11.3 cm, respectively, in the sniffing position, and to 3.39 cm and 9.59 cm, respectively, in the maximal flexion position (all P-values < 0.001). TV remained unchanged and was only dependent on age. After stratifying patients by age, similar results were observed with other distances. CT and CV increased by 1.099 cm and 0.909 cm, respectively, when head position changed from neutral head to sniffing position, and decreased by 0.947 cm and 0.838 cm, respectively, when head position changed from neutral head to maximal flexion. CONCLUSION: Change in head position can influence the depth of tracheal tube intubation. Therefore, the estimated depth should be corrected according to the surgical head position.

Mapping the amide-I vibrations of model dipeptides with secondary structure sensitivity and amino acid residue specificity, and its application to amyloid ß-peptide in aqueous solution.

Vibrational spectroscopy has been known as particularly well-suited for deciphering the polypeptide's structure. To decode structural information encoded in IR spectra, we developed amide-I frequency maps on the basis of model dipeptides to correlate the amide-I frequency of interest to the combination of the calculated secondary structure dependent amide-I frequency by using DFT method and the electrostatic potentials that projected onto the amide unit from the micro-environment within molecular mechanics force field. The constructed maps were applied to model dipeptides and amyloid ß-peptide fragment (Aß25-35). The dipeptide specified map (DS map) and the hybrid map (HYB map) predicted amide-I bands of Aß25-35 in solution satisfactorily reproduce experimental observation, and indicate the preference of forming ß-sheet and random coil structure for Aß25-35 in D2O just as the results of cluster analysis suggested. These maps with secondary structural sensitivity and amino acid residue specificity open up a way for the interpretation of amide-I vibrations and show their potentials in the understanding of molecular structure of polypeptides in solution.

Efficacy and safety of interscalene block combined with general anesthesia for arthroscopic shoulder surgery: A meta-analysis.

STUDY OBJECTIVE: There is controversy regarding the efficacy and safety of using interscalene block (ISB) combined with general anesthesia (GA) for arthroscopic shoulder surgery. Our meta-analysis was undertaken to evaluate the utility of this approach. MEASUREMENTS: We searched the PubMed, Cochrane Library, EMBASE, CNKI, VIP and ClinicalTrials.gov databases for randomized controlled trials. The primary endpoint was extubation time. Secondary endpoints included intraoperative heart rate, pain scores on the day of and 1 day after the operation, intraoperative systolic blood pressure and adverse events. MAIN RESULTS: Ten RCTs involving 746 patients undergoing arthroscopic shoulder surgery met inclusion criteria. Compared with GA alone, ISB + GA was associated with a shorter extubation time(WMD = -6.13; 95% CI = -8.68 to -3.57; P < 0.00001; I2 = 94%), a lower pain score on the day of the operation (WMD = -2.46; 95% CI = -4.53 to -0.40; P = 0.02; I2 = 97%), a lower pain score 1 day after the operation (WMD = -1.49; 95% CI = -2.46 to -0.52; P = 0.003; I2 = 88%), a lower intraoperative systolic blood pressure (WMD = -12.64; 95% CI = -20.90 to -4.39; P = 0.003; I2 = 95%), a lower heart rate (WMD = -8.81; 95% CI = -15.34 to -2.28; P = 0.008; I2 = 95%) and a lower incidence of adverse events (RR = 0.31; 95% CI = 0.15-0.66; P = 0.002; I2 = 32%). CONCLUSIONS: In patients undergoing arthroscopic shoulder surgery, ISB + GA is associated with a lower heart rate, lower pain scores on the day of and 1 day after the operation, a lower intraoperative systolic blood pressure, a shorter extubation time and a lower incidence of adverse events compared with GA alone.

Determination of tubuloside B by LC-MS/MS and its application to a pharmacokinetic study in rats.

Tubuloside B, a novel neuroprotective phenylethanoid, is a major active constituent of Cistanche tubulosa and Cistanche deserticola. A specific and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantification of tubuloside B in rat plasma. Sample preparation was conducted through a protein-precipitation extraction with methanol using tubuloside A as internal standard (IS). Chromatographic separation was achieved using a Capcell Pak C18 column (2.0 × 50 mm, 5 µm) with a mobile phase of methanol-10 mm ammonium acetate buffer (70:30, v/v) in an isocratic elution. Mass spectrometry analysis was performed in negative ionization mode with selected reaction monitoring transitions at m/z 665.1 → 160.9 for tubuloside B, and m/z 827.1 → 160.9 for IS. Calibration curves were linear over the range of 1.64-1640 ng/mL for plasma samples samples (R2 > 0.990). The lower limit of quantification (LLOQ) was 1.64 ng/mL. The intra- and inter-day accuracy was between 92.3 and 113.0% with the RSD <9.23% at all LLOQ and quality control levels. Finally, this method was successfully applied in the pharmacokinetics study of tubuloside B after intravenous administration.

Effect of SiO2 Spacer-Layer Thickness on Localized Surface Plasmon-Enhanced ZnO Nanorod Array LEDs.

Localized surface plasmon (LSP)-enhanced ultraviolet LEDs have been constructed via spin-coating Ag nanoparticles onto ZnO/SiO2 core/shell nanorod array/p-GaN heterostructures. Different from the previous reports where the dielectric spacer-layer thickness was determined only through photoluminescence (PL) characterization, the SiO2 shell thickness in this work is also optimized by actual electroluminescence (EL) measurements to maximize the enhancement. It is interesting to find that the enhancement ratios derived from PL and EL measurements demonstrate different thickness dependences on SiO2 shell: an optimal 3.5-fold PL enhancement was obtained at the SiO2 thickness of 16 nm, while an "abnormal" 7-fold EL enhancement was achieved at the thickness of 12 nm. Time-resolved spectroscopy studies, as well as theoretical estimations and numerical simulations, reveal that the higher-ratio EL enhancement stems from joint contributions, both internal-quantum-efficiency improvement induced by exciton-LSP coupling and light-extraction-efficiency improvement aroused by photon-LSP coupling.

Telomerase gene screening and telomere overhang detection in Chinese patients with myelodysplastic syndrome.

BACKGROUND: Telomerase disfunction leads to short telometric overhangs, potentially resulting in chromosome instability. AIMS: To better understand the role of overhang length in the progression of myelodysplastic syndrome (MDS). METHODS: Bone marrow samples of 62 Chinese MDS patients were screened for TERT and TERC gene variants. Overhangs length was investigated. RESULTS: No mutation was identified. MDS patients had shorter overhangs compared to controls. Abnormal karyotype ones had shorter overhang compared to normal. Telomeric overhang length decreased as IPSS/WPSS value increased. CONCLUSIONS: Overhang changes in accordance with IPSS/WPSS in MDS. Short overhang may be an independent factor for poor prognosis in MDS.

Telomerase gene mutation screening and telomere overhang detection in Chinese patients with acute myeloid leukemia.

Loss-of-function mutations in telomerase complex genes reduce telomerase activity, and can clinically manifest as bone marrow failure disease, which predisposes to acute myeloid leukemia (AML). Telomerase dysfunction also leads to short telomeric overhang, which is a crucial telomeric structural component, and potentially results in chromosome instability. We screened variants in telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) genes, and investigated the 3'-overhang length in bone marrow samples from 72 Chinese patients with AML (61 de novo, 11 secondary, excluding M3), aged 13-77. Cytogenetics, disease severity and short-term survival were evaluated. Three TERT mutations (n896G>A, n1079C>G and n1451G>C) were identified. Mutation carriers had short overhangs and a poor prognosis. We found that overhang lengths were much shorter in AML compared to normal controls (p < 0.001). Short overhangs were related to a high percentage of karyotype abnormalities and poor prognosis (73.8% in short overhang group vs. 30% in normal group, p=0.001). Multivariant analysis showed that overhang length, age and unfavorable chromosome abnormalities served as independent prognostic markers in AML (Cox regression, p=0.001). These data raise the possibility that short overhang length may predict poor prognosis in patients with AML. These findings would have to be confirmed in large, prospective studies.

[Porcine anti-human lymphocyte globulin plus cyclosporine A therapy for severe aplastic anemia].

OBJECTIVE: To evaluate the efficacy of porcine anti-human lymphocyte globulin (P-ALG) plus cyclosporine A (CsA) therapy for severe aplastic anemia (SAA). METHODS: Forty-eight SAA patients (31 males, 17 females) including 17 very severe aplastic anemias (vSAA) were treated with ALG plus CsA between 1999 to 2009 in our hospital and the outcomes were analyzed retrospectively for early mortality, response rate and quality, survival rate, toxicity and complications. RESULTS: The median age was 28 (13 - 64) years. The interval from diagnosis to treatment was 45 days. The median neutrophil count at diagnosis was 0.178 × 10(9)/L. Overall response was 83.3% (54.2% complete, 29.2% partial) with a median time of 90 (23 - 380) days. 10.4% died of infection within 30 days mainly of fungi infection. Only 1 patient relapsed 2 years after treatment. No clonal disease was found. The 1.5-year survival rate was 87.5%. vSAAs had less response, higher early mortality and less survival (64.7%, 29.4% and 51.8%, respectively) compared to that of SAA (93.5%, 0, 100%, respectively, P < 0.05). Grouped patients with different age, gender, intervals between diagnosis and treatment and pre-existing infections had similar response. The main side effects were fever and skin rash (52.1%), serum sickness (16.7%), impaired liver function (60.4%) and hemorrhage (2.1%). No treatment-related mortality was found. CONCLUSION: P-ALG plus CsA is an ideal and well tolerated treatment for SAA but not for vSAA.