Investigating the Immunogenic Cell Death-Dependent Subtypes and Prognostic Signature of Triple-Negative Breast Cancer.

Recently, immunotherapy has emerged as a promising and effective method for treating triple-negative breast cancer (TNBC). However, challenges still persist. Immunogenic cell death (ICD) is considered a prospective treatment and potential combinational treatment strategy as it induces an anti-tumor immune response by presenting the antigenic epitopes of dead cells. Nevertheless, the ICD process in TNBC and its impact on disease progression and the response to immunotherapy are not well understood. In this study, we observed dysregulation of the ICD process and verified the altered expression of prognostic ICD genes in TNBC through quantitative real-time polymerase chain reaction (qRT-PCR) analysis. To investigate the potential role of the ICD process in TNBC progression, we determined the ICD-dependent subtypes, and two were identified. Analysis of their distinct tumor immune microenvironment (TIME) and cancer hallmark features revealed that Cluster 1 and 2 corresponded to the immune "cold" and "hot" phenotypes, respectively. In addition, we constructed the prognostic signature ICD score of TNBC patients and demonstrated its clinical independence and generalizability. The ICD score could also serve as a potential biomarker for immune checkpoint blockade and may aid in the identification of targeted effective agents for individualized clinical strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00133-x.

Comparisons in analgesic effects between ultrasound-guided erector spinae plane block and surgical intercostal nerve block after video-assisted thoracoscopic surgery: A randomized controlled trial.

STUDY OBJECTIVE: This study aimed to compare the analgesic effects of anesthesiologist-administrated erector spinae plane block (ESPB) and surgeon-administrated intercostal nerve block (ICNB) following video-assisted thoracoscopic surgery (VATS). DESIGN: Randomized, controlled, double-blinded study. SETTING: Operating room, postoperative recovery room and ward in two centers. PATIENTS: One hundred patients, ASA I-III and scheduled for elective VATS. INTERVENTIONS: The anesthesiologist-administrated ESPB under ultrasound guidance or surgeon-administrated ICNB under video-assisted thoracoscopy was randomly provided during VATS. Regular oral non-opioid analgesic combined with intravenous rescue morphine were prescribed for multimodal analgesia after surgery. MEASUREMENTS: The primary outcomes were the pain score and morphine consumption during 48 h after surgery. Postoperative pain intensity were assessed using the 10-cm visual analogue scale at 1 h, 24 h, and 48 h after surgery. Morphine consumption at these time points was compared between the two study groups. Furthermore, oral weak opioid rescue analgesic was also provided at 24 h after surgery. Postoperative quality of recovery at 24 h was also assessed using the QoR-15 questionnaire, along with duration of chest tube drainage and hospital stay were compared as secondary outcomes. MAIN RESULTS: Patients in the two study groups had comparable baseline characteristics, and surgical types were also similar. Postoperative VAS changes at 1 h, 24 h, and 48 h after surgery were also comparable between the two study groups. Both groups had low median scores (<4.0) at all time points (all p > 0.05). Patients in the ESPB group required statistically non-significant higher 48-h morphine consumption [3 (0-6) vs. 0 (0-6) mg in the ESPB group and ICNB group respectively; p = 0.135] and lower numbers of oral rescue analgesic (0.4 ± 1.2 vs. 1.0 ± 1.8 in the ESPB group and ICNB group respectively; p = 0.059). Additionally, patients in the two study groups had similar QoR15 scores and lengths of hospital stay. CONCLUSIONS: Both anesthesiologist-administered ultrasound-guided ESPB and surgeon-administered VATS ICNB were effective analgesic techniques for patients undergoing VATS for tumor resection.

Immunocyte profiling changes in patients received epidural versus intravenous analgesia after pancreatectomy: A randomized controlled trial.

BACKGROUND: Perioperative immunosuppressants, such as surgical stress and opioid use may downregulate anti-cancer immunocytes for patients undergoing pancreatectomy. Thoracic epidural analgesia (TEA) may attenuate these negative effects and provide better anti-cancer immunocyte profile change than intravenous analgesia using opioid. METHODS: We randomly assigned 108 adult patients undergoing pancreatectomy to receive one of two 72-h postoperative analgesia protocols: one was TEA, and the other was intravenous patient-controlled analgesia (IV-PCA). The perioperative proportional changes of immunocytes relevant to anticancer immunity-namely natural killer (NK) cells, cytotoxic T cells, helper T cells, mature dendritic cells, and regulatory T (Treg) cells were determined at 1 day before surgery, at the end of surgery and on postoperative day 1,4 and 7 using flow cytometry. In addition, the progression-free survival and overall survival between the two groups were compared. RESULTS: After surgery, the proportions of NK cells and cytotoxic T cells were significantly decreased; the proportion of B cells and mature dendritic cells and Treg cells were significantly increased. However, the proportions of helper T cells exhibited no significant change. These results were comparable between the two groups. Furthermore, there were no significant differences in progression-free survival (52.75 [39.96] and 57.48 [43.66] months for patients in the TEA and IV-PCA groups, respectively; p = 0.5600) and overall survival (62.71 [35.48] and 75.11 [33.10] months for patients in the TEA and IV-PCA groups, respectively; p = 0.0644). CONCLUSIONS: TEA was neither associated with favorable anticancer immunity nor favorable oncological outcomes for patients undergoing pancreatectomy.

Integrated transcriptome and proteome analysis provides insights into CpFPA1 for floral induction in Chimonanthus praecox (Magnoliidae) without FLC in genome.

KEY MESSAGE: We used transcriptomic and proteomic association analysis to reveal the critical genes/proteins at three key flower bud differentiation stages and overexpression of CpFPA1 in Arabidopsis resulted in earlier flowering. Wintersweet (Chimonanthus praecox), a rare winter-flowering woody plant, is well known for its unique blooming time, fragrance and long flowering period. However, the molecular mechanism of flowering in C. praecox remains poorly unclear. In this study, we used transcriptomic and proteomic association analysis to reveal the critical genes/proteins at three key flower bud (FB) differentiation stages (FB.Apr, FB.May and FB.Nov) in C. praecox. The results showed that a total of 952 differential expressed genes (DEGs) and 40 differential expressed proteins (DEPs) were identified. Gene ontology (GO) enrichment revealed that DEGs in FB.Apr/FB.May comparison group were mainly involved in metabolic of biological process, cell and cell part of cellular component and catalytic activity of molecular function. In the EuKaryotic Orthologous Groups (KOG) functional classification, DEPs were predicted mainly in the function of general function prediction only (KOG0118), post-translational modification, protein turnover and chaperones. The autonomous pathway genes play an essential role in the floral induction. Based on transcriptome and proteome correlation analysis, six candidate genes associated with the autonomous pathway were identified, including FPA1, FPA2a, FPA2b, FCA, FLK, FY. Furthermore, CpFPA1 was isolated and functionally characterized, and ectopic expression of CpFPA1 in Arabidopsis Columbia (Col-0) resulted in earlier flowering. These data could contribute to understand the function of CpFPA1 for floral induction and provide information for further research on the molecular mechanisms of flowering in wintersweet.

Sakuranetin reduces inflammation and chondrocyte dysfunction in osteoarthritis by inhibiting the PI3K/AKT/NF-κB pathway.

Osteoarthritis (OA) is a prevalent degenerative disease that impairs limb function, and its pathogenesis is closely related to inflammation. Sakuranetin (SK) is a cherry flavonoid phytoalexin with potent anti-inflammatory, anti-oxidant, and ant-ifungal properties. In recent studies, flavonoid and phytoalexin-related medicines have shown promise in the treatment of OA. However, the effects of SK on chondrocyte inflammation and the chondrogenesis process have remained unexplored, as have its functions in OA treatment. This study sought to confirm the therapeutic effects of SK in the OA rat model and reveal the potential mechanisms for protecting chondrocytes. The relevant mechanisms of SK were analyzed by network pharmacology analysis. Chondrocytes were subjected to IL-1ß intervention to simulate an inflammatory environment and received SK treatment. Then, anabolism, catabolism, and inflammatory markers were detected by western blot, qPCR, elisa, and immunofluorescence. Chondrogenic ability was evaluated by micromass and 3D culture assays. The rats were treated with destabilization of the medial meniscus (DMM) surgery to establish an OA model and SK intra-articular injections subsequently. Histological staining, immunohistochemistry, and micro-CT were performed to analyze the structural and morphological changes of cartilage and subchondral bone. In chondrocytes, IL-1ß treatment reduced chondrogenic ability, promoted catabolism, and exacerbated inflammation by triggering the PI3K/AKT/NF-κB pathway, whereas SK treatment partially rescued these negative effects. In vivo, SK treatment effectively alleviated the degeneration of cartilage and subchondral bone, thereby delaying the progression of OA. In summary, SK alleviates chondrocyte inflammation and promotes chondrogenesis by inhibiting the PI3K/AKT/NF-κB pathway, thereby improving OA progression.

Effects of nonintubated thoracoscopic surgery on postoperative neurocognitive function: a randomized controlled trial.

OBJECTIVES: Postoperative neurocognitive disorder following thoracoscopic surgery with general anaesthesia may be linked to reduced intraoperative cerebral oxygenation and perioperative inflammation, which can potentially be exacerbated by mechanical ventilation. However, nonintubated thoracoscopic surgery, which utilizes regional anaesthesia and maintains spontaneous breathing, provides a unique model for studying the potential benefits of avoiding mechanical ventilation. This approach allows investigation into the impact on perioperative neurocognitive profiles, inflammatory responses and intraoperative cerebral oxygen levels. METHODS: In total, 110 patients undergoing thoracoscopic surgery were randomly equally assigned to the intubated group and the nonintubated group. Regional cerebral oxygenation was monitored during surgery. Serum neuroinflammatory biomarkers, including interleukin-6 and glial fibrillary acidic protein, were measured at baseline (before surgery) and 24 h after surgery. Postoperative complication severity was compared using the Comprehensive Complication Index. The primary outcome was perioperative changes in neurocognitive test score, which was assessed at baseline, 24 h and 6 months after surgery. RESULTS: Patients in the nonintubated group had higher neurocognitive test scores at 24 h (69.9 ± 10.5 vs 65.3 ± 11.8; P = 0.03) and 6 months (70.6 ± 6.7 vs 65.4 ± 8.1; P < 0.01) after surgery and significantly higher regional cerebral oxygenation over time during one-lung ventilation (P = 0.03). Patients in the intubated group revealed a significantly higher postoperative serum interleukin-6 level (group by time interaction, P = 0.04) and a trend towards a significantly higher serum glial fibrillary acidic protein level (group by time interaction, P = 0.11). Furthermore, patients in the nonintubated group had a significantly lower Comprehensive Complication Index (9.0 ± 8.2 vs 6.1 ± 7.1; P < 0.05). CONCLUSIONS: Nonintubated thoracoscopic surgery was associated with improved postoperative neurocognitive recovery, more stable intraoperative cerebral oxygenation, ameliorated perioperative inflammation and attenuated postoperative complication severity.

Alleviating effect of Nexrutine on mucosal inflammation in mice with ulcerative colitis: Involvement of the RELA suppression.

BACKGROUND: Nexrutine is an herbal extract derived from Phellodendron amurense, known for its anti-inflammatory, antidiarrheal, and hemostatic properties. However, its effect on ulcerative colitis (UC) remains unclear. METHODS: A mouse model of UC was induced by 3% dextran sulfate sodium, while human colonic epithelial cells NCM-460 were exposed to lipopolysaccharide. Both models were treated with Nexrutine at 300 or 600 mg/kg, with Mesalazine applied as a positive control regimen. The disease activity index (DAI) of mice was calculated, and the pathological injury scores were assessed through hematoxylin and eosin staining. The viability of NCM-460 cells was determined using the CCK-8 method. Inflammatory cytokines were detected using ELISA kits. Expression of mucin 3 (MUC3), Claudin-1, and tight junction protein (ZO-1) was detected to analyze mucosal barrier integrity. Target genes of Nexrutine were predicted using bioinformatics tools. Expression of RELA proto-oncogene (RELA) was analyzed using qPCR and western blot assays. RESULTS: The Nexrutine treatments significantly alleviated DAI of mice, mitigated pathological changes in their colon tissues, decreased the production of pro-inflammatory cytokines, enhanced the barrier integrity-related proteins, and increased NCM-460 cell viability in vitro. RELA, identified as a target gene of Nexrutine, showed elevated levels in UC models but was substantially suppressed by Nexrutine treatment. Adenovirus-mediated RELA upregulation in mice or the overexpression plasmid of RELA in cells counteracted the effects of Nexrutine treatments, exacerbating UC-related symptoms. CONCLUSION: This study demonstrates that Nexrutine alleviates inflammatory mucosal barrier damage in UC by suppressing RELA transcription.

Activity of Gut-Derived Nisin-like Lantibiotics against Human Gut Pathogens and Commensals.

Recent advances in sequencing techniques unveiled the vast potential of ribosomally synthesized and post-translationally modified peptides (RiPPs) encoded in microbiomes. Class I lantibiotics such as nisin A, widely used as a food preservative, have been investigated for their efficacy in killing pathogens. However, the impact of nisin and nisin-like class I lantibiotics on commensal bacteria residing in the human gut remains unclear. Here, we report six gut-derived class I lantibiotics that are close homologues of nisin, four of which are novel. We applied an improved lantibiotic expression platform to produce and purify these lantibiotics for antimicrobial assays. We determined their minimal inhibitory concentration (MIC) against both Gram-positive human pathogens and gut commensals and profiled the lantibiotic resistance genes in these pathogens and commensals. Structure-activity relationship (SAR) studies with analogs revealed key regions and residues that impact their antimicrobial properties. Our characterization and SAR studies of nisin-like lantibiotics against both pathogens and human gut commensals could shed light on the future development of lantibiotic-based therapeutics and food preservatives.

Electroencephalographic spectrogram-guided total intravenous anesthesia using dexmedetomidine and propofol prevents unnecessary anesthetic dosing during craniotomy: a propensity score-matched analysis.

BACKGROUND: The bispectral index (BIS) may be unreliable to gauge anesthetic depth when dexmedetomidine is administered. By comparison, the electroencephalogram (EEG) spectrogram enables the visualization of the brain response during anesthesia and may prevent unnecessary anesthetic consumption. METHODS: This retrospective study included 140 adult patients undergoing elective craniotomy who received total intravenous anesthesia using a combination of propofol and dexmedetomidine infusions. Patients were equally matched to the spectrogram group (maintaining the robust EEG alpha power during surgery) or the index group (maintaining the BIS score between 40 and 60 during surgery) based on the propensity score of age and surgical type. The primary outcome was the propofol dose. Secondary outcome was the postoperative neurological profile. RESULTS: Patients in the spectrogram group received significantly less propofol (1585 ± 581 vs. 2314 ± 810 mg, P < 0.001). Fewer patients in the spectrogram group exhibited delayed emergence (1.4% vs. 11.4%, P = 0.033). The postoperative delirium profile was similar between the groups (profile P = 0.227). Patients in the spectrogram group exhibited better in-hospital Barthel's index scores changes (admission state: 83.6 ± 27.6 vs. 91.6 ± 17.1; discharge state: 86.4 ± 24.3 vs. 85.1 ± 21.5; group-time interaction P = 0.008). However, the incidence of postoperative neurological complications was similar between the groups. CONCLUSIONS: EEG spectrogram-guided anesthesia prevents unnecessary anesthetic consumption during elective craniotomy. This may also prevent delayed emergence and improve postoperative Barthel index scores.

Interfacial Crack Growth-Based Fatigue Lifetime Prediction of Thermoelectric Modules under Thermal Cycling.

As a result of the complexity and difficulty of the lifetime assessment of the thermoelectric (TE) module, the related research is still immature. In this work, to predict the lifetime of the Bi2Te3-based TE module from the perspective of cyclic thermal stress leading to interface cracking, the viscoplastic behavior of the solder layer is first described by the Anand material ontology model, and then the sprouting and expansion of interface cracking of the module are simulated by combining the Darveaux model and the viscoplastic dissipation energy accumulated during the thermal stress cyclic loading. After that, the complete lifetime prediction model of the TE module is established on the basis of the thermal cycling experiments and the finite element simulation calculation data, which can simply and efficiently predict the cycle number of the module resistance rise and its rise rate. The prediction deviations are 6.1 and 6.7%, respectively, verifying the feasibility of the model. The work in this paper can provide a reference for the life evaluation of TE modules.

Investigation into the mechanism of action of the antimicrobial peptide epilancin 15X.

Addressing the current antibiotic-resistance challenge would be aided by the identification of compounds with novel mechanisms of action. Epilancin 15X, a lantibiotic produced by Staphylococcus epidermidis 15 × 154, displays antimicrobial activity in the submicromolar range against a subset of pathogenic Gram-positive bacteria. S. epidermidis is a common member of the human skin or mucosal microbiota. We here investigated the mechanism of action of epilancin 15X. The compound is bactericidal against Staphylococcus carnosus as well as Bacillus subtilis and appears to kill these bacteria by membrane disruption. Structure-activity relationship studies using engineered analogs show that its conserved positively charged residues and dehydroamino acids are important for bioactivity, but the N-terminal lactyl group is tolerant of changes. Epilancin 15X treatment negatively affects fatty acid synthesis, RNA translation, and DNA replication and transcription without affecting cell wall biosynthesis. The compound appears localized to the surface of bacteria and is most potent in disrupting the membranes of liposomes composed of negatively charged membrane lipids in a lipid II independent manner. Epilancin 15X does not elicit a LiaRS response in B. subtilis but did upregulate VraRS in S. carnosus. Treatment of S. carnosus or B. subtilis with epilancin 15X resulted in an aggregation phenotype in microscopy experiments. Collectively these studies provide new information on epilancin 15X activity.

Platycodin D induces neutrophil apoptosis by downregulating PD-L1 expression to inhibit breast cancer pulmonary metastasis.

During breast cancer development, programmed cell death 1 ligand 1 (PD-L1) overexpression in neutrophils leads to delayed apoptosis and promotes neutrophil hyperproliferation in the lung to form a premetastatic niche, which is beneficial for pulmonary metastasis. Platycodin D (PlaD), a triterpenoid saponin with known anti-inflammatory and antitumor effects, has been reported to downregulate PD-L1 expression. This study aimed to investigate the inhibitory effect of PlaD on neutrophil PD-L1 in 4 T1 tumor-bearing mice and the potential mechanism of breast cancer pulmonary metastasis. In this study, the orthotopic 4 T1 murine mammary carcinoma model was administered 10 and 20 mg/kg PlaD by gavage. PlaD reduced the excess neutrophils and decreased their high migratory capacity in bone marrow, peripheral blood and lung tissue in the premetastatic period, thereby effectively inhibiting tumor growth and pulmonary metastasis. Moreover, PlaD inhibited the phosphatidylinositol-3-kinase (PI3K)/Akt pathway by decreasing the expression of PD-L1 in neutrophils and promoted neutrophil apoptosis. In vitro, PlaD treatment decreased the viability and inhibited migration of neutrophil-like dHL-60 in a dose-dependent manner. Similarly, PlaD inhibited the increase in PD-L1 induced by IFN-γ stimulation and subsequently induced apoptosis in dHL-60 cells. In conclusion, the administration of PlaD inhibited the PI3K/Akt signaling pathway by reducing the expression of PD-L1 in neutrophils. PlaD promoted neutrophil apoptosis, thereby inhibiting the establishment of a premetastatic niche and ultimately blocking the development of pulmonary metastasis.

Periodic event-triggered dynamic output feedback control for networked control systems subject to packet dropouts.

This paper proposes a co-design method of dynamic output feedback control law and periodic event-triggered control (PETC) strategy to tolerate a maximum allowable number of successive packet dropouts (MANSDs) in networked control systems (NCSs). For the purpose of striking a balance between saving limited communication resources and reducing complexity of the transmission implementation, we present the periodic event-triggering mechanism (PETM), in which the triggering conditions only needs to be monitored at each event-verifying instant. In NCSs, packets often suffer from some interference in network transmission, such as packet losses. For packet dropouts, we introduce a dropout variable and model the whole closed-loop systems as a hybrid system. Furthermore, some stability conditions for co-design are given by a novel Lyapunov function and stability theorems of hybrid systems, and the explicit designs parameters of controller and triggering conditions are presented to ensure L2 stability. Finally, two illustrated examples are given to show the effectiveness of the proposed design methods.

Dry Nutrition Delivery System Based on Defatted Soybean Particles and Its Application with ß-Carotene.

Many nutrition delivery systems (NDSs) have been developed for the encapsulation, protection, and delivery of bioactive compounds, such as ß-carotene. Most of those systems were prepared in solution, which is inconvenient for transportation and storage in the food industry. In the present work, we constructed an environmentally friendly dry NDS based on defatted soybean particles (DSPs) by milling a ß-carotene-DSP mixture. The loading efficiency of the NDS reached 89.0%, and the cumulative release rate decreased from 15.1% (free ß-carotene) to 6.0% within 8 h. The stability of ß-carotene in the dry NDS was found to have increased in a thermogravimetric analysis. Stored for 14 days at 55 °C or under UV irradiation, the retaining rates of ß-carotene in the NDS increased to 50.7% and 63.6%, respectively, while they were 24.2% and 54.6% for the free samples. The bioavailability of ß-carotene was improved by the NDS too. The apparent permeability coefficient of the NDS reached 1.37 × 10-6 cm/s, which is 12 times that of free ß-carotene (0.11 × 10-6 cm/s). Besides being environmentally friendly, the dry NDS can facilitate carriage, transportation, or storage in the food industry, and similar to other NDSs, it improves the stability and bioavailability of nutrients.

Improved production of class I lanthipeptides in Escherichia coli.

Lanthipeptides are ribosomally synthesised and post-translationally modified peptides containing lanthionine (Lan) and methyllanthionine (MeLan) residues that are formed by dehydration of Ser/Thr residues followed by conjugate addition of Cys to the resulting dehydroamino acids. Class I lanthipeptide dehydratases utilize glutamyl-tRNAGlu as a co-substrate to glutamylate Ser/Thr followed by glutamate elimination. Here we report a new system to heterologously express class I lanthipeptides in Escherichia coli through co-expression of the producing organism's glutamyl-tRNA synthetase (GluRS) and tRNAGlu pair in the vector pEVOL. In contrast to the results in the absence of the pEVOL system, we observed the production of fully-dehydrated peptides, including epilancin 15X, and peptides from the Bacteroidota Chryseobacterium and Runella. A second common obstacle to production of lanthipeptides in E. coli is the formation of glutathione adducts. LanC-like (LanCL) enzymes were previously reported to add glutathione to dehydroamino-acid-containing proteins in Eukarya. Herein, we demonstrate that the LanCL enzymes can remove GSH adducts from C-glutathionylated peptides with dl- or ll-lanthionine stereochemistry. These two advances will aid synthetic biology-driven genome mining efforts to discover new lanthipeptides.

Validation of Chinese version of a global anesthetic recovery questionnaire: A multicenter observational trial on ObsQoR-11.

BACKGROUND: The obstetric quality of recovery (ObsQoR-11) is considered one of the best patient-reported outcome measures of post-cesarean recovery. However, it has been neither validated in Chinese nor evaluated at >24 h after delivery. METHODS: Parturients from three hospitals (n = 279) completed the Chinese ObsQoR-11 at 24 h (T1) and 96 h (T2) after elective cesarean delivery. Convergent validity was assessed by correlation of Chinese ObsQoR-11 with a 100-mm numerical rating scale (NRS) of general health status; discriminant validity of good recovery (NRS ≥ 70-mm); and construct validity by correlation with influential factors to post-cesarean recovery. The reliability and responsiveness were also assessed. RESULTS: The Chinese ObsQoR-11 correlated moderately with the NRS [T1: r = 0.38 (95% confidence interval: 0.28-0.48), p < 0.0001; T2: r = 0.43 (95% confidence interval: 0.32-0.52), p < 0.0001] and discriminated between good and poor recovery [T1: mean (SD) score: 64 (20) vs 49 (17), p < 0.0001; T2: median (IQR) score: 81 (66-94) vs. 61 (53-72); p = 0.0002]; weakly correlated with gestational age, successful breastfeeding, and operation time. It was reliable (internal consistency: 0.75 (T1) and 0.82 (T2); split-half: 0.77 (T1) and 0.85 (T2); test-retest intraclass correlation coefficient r > 0.6 for each item) and responsive (Cohen effect size: 0.88; standardized response mean: 0.81). CONCLUSION: The Chinese ObsQoR-11may be used for assessing recovery at 24 h and 96 h after cesarean delivery. However, its' cutoff value for good recovery may be lower than that of other versions.

Effects of Goal-Directed Hemodynamic Therapy Using a Noninvasive Finger-Cuff Monitoring Device on Intraoperative Cerebral Oxygenation and Early Delayed Neurocognitive Recovery in Patients Undergoing Beach Chair Position Shoulder Surgery: A Randomized Controlled Trial.

BACKGROUND: Perioperative cerebral desaturation events (CDEs) and delayed neurocognitive recovery are common among patients undergoing beach chair position (BCP) shoulder surgery and may be caused by cerebral hypoperfusion. This study tested the hypothesis that the application of goal-directed hemodynamic therapy (GDHT) would attenuate these conditions. METHODS: We randomly assigned 70 adult patients undergoing BCP shoulder surgery to GDHT group or control at a 1:1 ratio. Cerebral oxygenation was monitored using near-infrared spectroscopy, and GDHT was administered using the ClearSight pulse wave analysis system. The primary outcome was CDE duration, whereas the secondary outcomes were CDE occurrence, delayed neurocognitive recovery occurrence, and Taiwanese version of the Quick Mild Cognitive Impairment (Qmci-TW) test score on the first postoperative day (T 2 ) adjusted for the baseline score (on the day before surgery; T 1 ). RESULTS: CDE duration was significantly shorter in the GDHT group (0 [0-0] vs 15 [0-75] min; median difference [95% confidence interval], -8 [-15 to 0] min; P = .007). Compared with the control group, fewer patients in the GDHT group experienced CDEs (23% vs 51%; relative risk [95% confidence interval], 0.44 [0.22-0.89]; P = .025) and mild delayed neurocognitive recovery (17% vs 40%; relative risk [95% confidence interval], 0.60 [0.39-0.93]; P = .034). The Qmci-TW scores at T 2 adjusted for the baseline scores at T 1 were significantly higher in the GDHT group (difference in means: 4 [0-8]; P = .033). CONCLUSIONS: Implementing GDHT using a noninvasive finger-cuff monitoring device stabilizes intraoperative cerebral oxygenation and is associated with improved early postoperative cognitive scores in patients undergoing BCP shoulder surgery.

Delay of Surgery for Spinal Metastasis due to the COVID-19 Outbreak Affected Patient Outcomes.

OBJECTIVE: The present study is to analyze the effects of the coronavirus disease 2019 (COVID 2019) outbreak and the subsequent lockdown on the outcomes of spinal metastasis patients. METHODS: The study was a retrospective analysis of data from a prospective cohort study. All patients underwent surgical intervention for spinal metastases between January 2019 and December 2021 and had at least 3 months of postoperative follow-up. The primary outcome was overall mortality during the 4 different stages (pre-COVID-19 era, COVID-19 pandemic except in Taiwan, national lockdown, lifting of the lockdown). The secondary outcomes were the oncological severity scores, medical/surgical accessibility, and patient functional outcome during the 4 periods as well as survival/mortality. RESULTS: A total of 233 patients were included. The overall mortality rate was 41.20%. During the Taiwan lockdown, more patients received palliative surgery than other surgical methods, and no total en bloc spondylectomy was performed. The time from surgeon visit to operation was approximately doubled after the COVID-19 outbreak in Taiwan (75.97, 86.63, 168.79, and 166.91 hours in the 4 periods, respectively). The estimated survival probability was highest after the national lockdown was lifted and lowest during the lockdown. In the multivariate analysis, increased risk of mortality was observed with delay of surgery, with emergency surgery having a higher risk with delays above 33 hours, urgent surgery (below 59 and above 111 hours), and elective surgery (above 332 hours). CONCLUSION: The COVID-19 pandemic and related policies have altered daily clinical practice and negatively impacted the survival of patients with spinal metastases.