Enhanced reliability and time efficiency of deep learning-based posterior tibial slope measurement over manual techniques.

PURPOSE: Multifaceted factors contribute to inferior outcomes following anterior cruciate ligament (ACL) reconstruction surgery. A particular focus is placed on the posterior tibial slope (PTS). This study introduces the integration of machine learning and artificial intelligence (AI) for efficient measurements of tibial slopes on magnetic resonance imaging images as a promising solution. This advancement aims to enhance risk stratification, diagnostic insights, intervention prognosis and surgical planning for ACL injuries. METHODS: Images and demographic information from 120 patients who underwent ACL reconstruction surgery were used for this study. An AI-driven model was developed to measure the posterior lateral tibial slope using the YOLOv8 algorithm. The accuracy of the lateral tibial slope, medial tibial slope and tibial longitudinal axis measurements was assessed, and the results reached high levels of reliability. This study employed machine learning and AI techniques to provide objective, consistent and efficient measurements of tibial slopes on MR images. RESULTS: Three distinct models were developed to derive AI-based measurements. The study results revealed a substantial correlation between the measurements obtained from the AI models and those obtained by the orthopaedic surgeon across three parameters: lateral tibial slope, medial tibial slope and tibial longitudinal axis. Specifically, the Pearson correlation coefficients were 0.673, 0.850 and 0.839, respectively. The Spearman rank correlation coefficients were 0.736, 0.861 and 0.738, respectively. Additionally, the interclass correlation coefficients were 0.63, 0.84 and 0.84, respectively. CONCLUSION: This study establishes that the deep learning-based method for measuring posterior tibial slopes strongly correlates with the evaluations of expert orthopaedic surgeons. The time efficiency and consistency of this technique suggest its utility in clinical practice, promising to enhance workflow, risk assessment and the customization of patient treatment plans. LEVEL OF EVIDENCE: Level III, cross-sectional diagnostic study.

Correlation between higher lateral tibial slope and inferior long term subjective outcomes following single bundle anterior cruciate ligament reconstruction.

BACKGROUND: The impact of anatomical factors, such as the lateral tibial slope (LTS), on outcomes following anterior cruciate ligament (ACL) reconstruction is an area of growing interest. This study was led by the observation that patients with a higher LTS may have different recovery trajectories. HYPOTHESIS/PURPOSE: The purpose of this study was to investigate the correlation between a higher LTS and long term subjective outcomes following single-bundle ACL reconstruction. STUDY DESIGN: This study was designed as a retrospective cohort study. METHODS: The study comprised 138 patients who underwent single-bundle ACL reconstruction. The LTS was measured on preoperative radiographs. Patient-reported outcome measures (PROMs) were collected, which included the Lysholm Knee Score, UCLA Activity Score, IKDC Score, and Tegner Activity Score, over a mean follow-up duration of 137 months. RESULTS: A significant negative correlation was found between LTS and all measured PROMs (p < 0.001). The established cut-off value of LTS distinguishing between "Good" and "Fair" Lysholm scores was 8.35 degrees. Female patients have statistically significant higher LTS and lower PROMs scores than male. Patients with LTS greater than or equal to 8.35 had significantly lower PROMs, indicative of poorer functional and subjective outcomes. CONCLUSION: Our findings suggest that a higher LTS is associated with inferior subjective outcomes following single-bundle ACL reconstruction in long term. The LTS cut-off value of 8.35 degrees could potentially be used as a reference in preoperative planning and patient counseling. CLINICAL RELEVANCE: Understanding the relationship between LTS and ACL reconstruction outcomes could inform surgical planning and postoperative management. These findings highlight the need to consider anatomical variances, such as LTS, when assessing patient-specific risks and recovery expectations, contributing to the advancement of personalized care in sports medicine.

The increased lateral tibial slope may result in inferior long-term clinical outcome after DB-ACL reconstruction.

PURPOSE: To determine if there is a correlation between lateral tibial slope and long-term clinical results in patients who underwent double-bundle ACL reconstruction. METHODS: We retrospectively reviewed patients that received double-bundle ACL reconstruction at a single institution by a single surgeon from January 2011 to December 2014. All the magnetic resonance imaging were reviewed and lateral tibial slopes (LTS) were recorded by an experienced surgeon and rechecked by the other two authors of this study that specialized in orthopedic knee surgery. The relationship between PROMs measurement and lateral tibial slope were analyzed. The patients were then separated into two groups (LTS > 7.4° and < 7.4°) according to the previous study. RESULTS: A total of 119 patients were enrolled in this study. All enrolled patients were followed for at least 8 years. The PROMS result were negatively correlated with the lateral tibial slope (p values all < 0.001). The patients with high lateral tibial slope had significantly lower PROMS values (Lysholm 94.26 ± 5.61 vs 80.15 ± 8.28, p = 0.013; IKDC 82.99 ± 4.55 vs 70.09 ± 7.15, p = 0.003; Tegner 9.32 ± 0.95 vs 6.85 ± 1.99, p < 0.001). Finally, the LTS cutoff value between patients with "Good" and "Fair" Lysholm score in our study was 7.55 degrees. CONCLUSIONS: Patients with high lateral tibial slope may result in inferior long-term subjective outcomes. The using of double-bundle ACL reconstruction along cannot overcome the negative impact caused by steep lateral tibial slope. A lateral tibial slope of 7.55° may be used as a cut-off for a good clinical outcome. LEVEL OF EVIDENCE: III retrospective comparative prognostic trial.

Efficacy and safety of dapagliflozin for treating heart failure in China: A meta-analysis.

This study assesses the efficacy and safety of dapagliflozin in Chinese patients with heart failure through a systematic review of randomized controlled trials from PubMed and the China National Knowledge Infrastructure databases. Focusing on 977 patients across eight trials, the meta-analysis used Review Manager 5.4.1 for data analysis. Key findings include a significant reduction in N-terminal pro-B-type natriuretic peptide levels (standardized mean difference: -2.88, 95% CI: -4.31 to -1.44, p<0.001) and an increase in left ventricular ejection fraction (weighted mean difference: 5.10, 95% CI: 2.32 to 10.32, p<0.001). However, changes in left ventricular end-diastolic diameter were not significant (weighted mean difference: -1.33, 95% CI: -2.80 to 0.15, p=0.08) and the relative risk of adverse reactions was comparable between the control and observation groups (RR: 1.17, 95% CI: 0.82 to 1.68, p=0.38). Overall, dapagliflozin demonstrates good efficacy and safety in treating heart failure in this population.

Cardiac-targeted PIASy gene silencing mediates deSUMOylation of caveolin-3 and prevents ischemia/reperfusion-induced Nav1.5 downregulation and ventricular arrhythmias.

BACKGROUND: Abnormal myocardial Nav1.5 expression and function cause lethal ventricular arrhythmias during myocardial ischemia-reperfusion (I/R). Protein inhibitor of activated STAT Y (PIASy)-mediated caveolin-3 (Cav-3) SUMO modification affects Cav-3 binding to the voltage-gated sodium channel 1.5 (Nav1.5). PIASy activity is increased after myocardial I/R, but it is unclear whether this is attributable to plasma membrane Nav1.5 downregulation and ventricular arrhythmias. METHODS: Using recombinant adeno-associated virus subtype 9 (AAV9), rat cardiac PIASy was silenced using intraventricular injection of PIASy short hairpin RNA (shRNA). After two weeks, rat hearts were subjected to I/R and electrocardiography was performed to assess malignant arrhythmias. Tissues from peri-infarct areas of the left ventricle were collected for molecular biological measurements. RESULTS: PIASy was upregulated by I/R (P < 0.01), with increased SUMO2/3 modification of Cav-3 and reduced membrane Nav1.5 density (P < 0.01). AAV9-PIASy shRNA intraventricular injection into the rat heart downregulated PIASy after I/R, at both mRNA and protein levels (P < 0.05 vs. Scramble-shRNA + I/R group), decreased SUMO-modified Cav-3 levels, enhanced Cav-3 binding to Nav1.5, and prevented I/R-induced decrease of Nav1.5 and Cav-3 co-localization in the intercalated disc and lateral membrane. PIASy silencing in rat hearts reduced I/R-induced fatal arrhythmias, which was reflected by a modest decrease in the duration of ventricular fibrillation (VF; P < 0.05 vs. Scramble-shRNA + I/R group) and a significantly reduced arrhythmia score (P < 0.01 vs. Scramble-shRNA + I/R group). The anti-arrhythmic effects of PIASy silencing were also evidenced by decreased episodes of ventricular tachycardia (VT), sustained VT and VF, especially at the time 5-10 min after ischemia (P < 0.05 vs. Scramble-shRNA + IR group). Using in vitro human embryonic kidney 293 T (HEK293T) cells and isolated adult rat cardiomyocyte models exposed to hypoxia/reoxygenation (H/R), we confirmed that increased PIASy promoted Cav-3 modification by SUMO2/3 and Nav1.5/Cav-3 dissociation after H/R. Mutation of SUMO consensus lysine sites in Cav-3 (K38R or K144R) altered the membrane expression levels of Nav1.5 and Cav-3 before and after H/R in HEK293T cells. CONCLUSIONS: I/R-induced cardiac PIASy activation increased Cav-3 SUMOylation by SUMO2/3 and dysregulated Nav1.5-related ventricular arrhythmias. Cardiac-targeted PIASy silencing mediated Cav-3 deSUMOylation and partially prevented I/R-induced Nav1.5 downregulation in the plasma membrane of cardiomyocytes, and subsequent ventricular arrhythmias in rats. PIASy was identified as a potential therapeutic target for life-threatening arrhythmias in patients with ischemic heart diseases.

Effect of Subcostal Anterior Quadratus Lumborum Block vs. Oblique Subcostal Transversus Abdominis Plane Block after Laparoscopic Radical Gastrectomy.

OBJECTIVE: To evaluate the analgesic effect of ultrasound-guided subcostal anterior quadratus lumborum block (QLB) for laparoscopic radical gastrectomy surgery. METHODS: Patients (aged 20-65 years, ASA I - II, and weighing 40-75 kg) scheduled for elective laparoscopic radical gastrectomy were enrolled in the current study. Sixty patients were randomly assigned to two groups by computer-generated randomization codes: an ultrasound-guided oblique subcostal transversus abdominis plane block (TAPB) group (group T, n=30) or an ultrasound-guided subcostal anterior QLB group (group Q, n=30). In both groups, bilateral ultrasound-guided oblique subcostal TAPB and subcostal anterior QLB were performed before general anesthesia with 0.25% ropivacaine 0.5 mL/kg. For postoperative management, all patients received patient-controlled intravenous analgesia (PCIA) with nalbuphine and sufentanil after surgery, maintaining visual analogue scale (VAS) scores ≤4 within 48 h. The intraoperative consumption of remifentanil, the requirement for sufentanil as a rescue analgesic, and the VAS scores at rest and coughing were recorded at 1, 6, 12, 24 and 48 h after surgery. The recovery (extubation time after surgery, first ambulation time, first flatus time and length of postoperative hospital stay) and the adverse events (nausea and vomiting, skin pruritus, respiratory depression and nerve-block related complications) were observed and recorded. The primary outcome was the perioperative consumption of opioids. RESULTS: Compared with group T, the intraoperative consumption of remifentanil, requirement for sufentanil and the frequency of PCIA were reduced in group Q. Meanwhile, VAS scores at all points of observation were significantly lower in group Q than in group T. Patients in group Q were also associated with shorter time to first out-of-bed activity and flatus, and shorter length of postoperative hospital stay than group T (P<0.05). There were no skin pruritus, respiratory depression or nerve-block related complications in both groups. CONCLUSION: Compared with ultrasound-guided oblique subcostal TAPB, ultrasound-guided subcostal anterior QLB provided greater opioid-sparing effect, lower visual analogue scores, and shorter postoperative hospital stay for laparoscopic radical gastrectomy.

Maresin1 Promotes M2 Macrophage Polarization Through Peroxisome Proliferator-Activated Receptor-γ Activation to Expedite Resolution of Acute Lung Injury.

BACKGROUND: Acute lung injury (ALI), manifested by progressive hypoxemia and respiratory distress, is associated with high morbidity and mortality, which lacks the effective therapies in clinics. Our previous studies demonstrated that maresin1 (MaR1), a specialized proresolving mediator, could effectively mitigate the inflammation of lipopolysaccharide (LPS)-induced ALI. However, whether MaR1 impacts the macrophage polarization to alleviate ALI remains unclear. Our study explored the effects and underlying mechanisms of MaR1 on the macrophage phenotypes in ALI. MATERIAL AND METHODS: Male BALB/c mice were subjected to endotracheal instillation of LPS to induce ALI and then intravenously injected with MaR1 or normal saline. Intraperitoneal administration of peroxisome proliferator-activated receptor-γ (PPAR-γ) inhibitor GW9662 was given 30 mins before MaR1. We measured the pathohistologic changes, pulmonary edema, inflammatory cytokines, and the flow cytometry of macrophage phenotypes. RESULTS: Our results illustrated that MaR1 ameliorated lung injury and increased monocyte or macrophage recruitment and the release of anti-inflammatory cytokines. The flow cytometry showed that MaR1 promoted polarization of CD11c-CD206+ (M2) macrophages and inhibited polarization of CD11c+CD206- (M1) macrophages. Besides, the western blotting revealed that MaR1 increased the expression of PPAR-γ. The pretreatment with PPAR-γ antagonist GW9662 could significantly suppress the polarization of M2 macrophages and antagonize the protective effects of MaR1 on LPS-stimulated ALI. CONCLUSIONS: MaR1 was able to promote M2 macrophage polarization by reversing LPS-mediated PPAR-γ inhibition, thereby expediting the recovery of LPS-stimulated ALI.

Co-expression Network Analysis Identifies Fourteen Hub Genes Associated with Prognosis in Clear Cell Renal Cell Carcinoma.

Renal cancer is a common genitourinary malignance, of which clear cell renal cell carcinoma (ccRCC) has high aggressiveness and leads to most cancer-related deaths. Identification of sensitive and reliable biomarkers for predicting tumorigenesis and progression has great significance in guiding the diagnosis and treatment of ccRCC. Here, we identified 2397 common differentially expressed genes (DEGs) using paired normal and tumor ccRCC tissues from GSE53757 and The Cancer Genome Atlas (TCGA). Then, we performed weighted gene co-expression network analysis and protein-protein interaction network analysis, 17 candidate hub genes were identified. These candidate hub genes were further validated in GSE36895 and Oncomine database and 14 real hub genes were identified. All the hub genes were up-regulated and significantly positively correlated with pathological stage and histologic grade of ccRCC. Survival analysis showed that the higher expression level of each hub gene tended to predict a worse clinical outcome. ROC analysis showed that all the hub genes can accurately distinguish between tumor and normal samples, and between early stage and advanced stage ccRCC. Moreover, all the hub genes were positively associated with distant metastasis, lymph node infiltration, tumor recurrence and the expression of MKi67, suggesting these genes might promote tumor proliferation, invasion and metastasis. Furthermore, the functional annotation demonstrated that most genes were enriched in cell-cycle related biological function. In summary, our study identified 14 potential biomarkers for predicting tumorigenesis and progression, which might contribute to early diagnosis, prognosis prediction and therapeutic intervention.

CXCL14 Overexpression Attenuates Sepsis-Associated Acute Kidney Injury by Inhibiting Proinflammatory Cytokine Production.

CXCL14 is a relatively novel chemokine with a wide spectrum of biological activities. The present study was designed to investigate whether CXCL14 overexpression attenuates sepsis-associated acute kidney injury (AKI) in mice. Sepsis model has been established by cecal ligation and puncture (CLP). CLP induced AKI in mice as assessed by increased renal neutrophil gelatinase-associated lipocalin (NGAL) expression and serum creatinine levels. We found that renal CXCL14 expression in the kidney was significantly decreased at 12 hours after CLP. Correlation analysis demonstrated a negative association between renal CXCL14 expression and AKI markers including serum creatinine and renal NGAL. Moreover, CXCL14 overexpression reduced cytokine (TNF-α, IL-6, and IL-1ß) production and NGAL expression in the kidney and decreased serum creatinine levels. In vivo and in vitro experiments found that CXCL14 overexpression inhibited M1 macrophage polarization but increased M2 polarization. Together, these results suggest that CXCL14 overexpression attenuates sepsis-associated AKI probably through the downregulation of macrophages-derived cytokine production. However, further studies are required to elucidate the underlying mechanism.

A Splice Variant of NCOR2, BQ323636.1, Confers Chemoresistance in Breast Cancer by Altering the Activity of NRF2.

Breast cancer is the most common type of female cancer. Reactive oxygen species (ROS) are vital in regulating signaling pathways that control cell survival and cell proliferation. Chemotherapeutic drugs such as anthracyclines induce cell death via ROS induction. Chemoresistance development is associated with adaptive response to oxidative stress. NRF2 is the main regulator of cytoprotective response to oxidative stress. NRF2 can enhance cell growth, antioxidant expression, and chemoresistance by providing growth advantage for malignant cells. Previously, we identified BQ323636.1 (BQ), a novel splice variant of nuclear co-repressor NCOR2, which can robustly predict tamoxifen resistance in primary breast cancer. In this study, we found that BQ was overexpressed in epirubicin-resistant cells and demonstrated that BQ overexpression could reduce the levels of epirubicin-induced ROS and confer epirubicin resistance. In vivo analysis using tissue microarray of primary breast cancer showed direct correlation between BQ expression and chemoresistance. In vitro experiments showed BQ could modulate NRF2 transcriptional activity and upregulate antioxidants. Luciferase reporter assays showed that although NCOR2 repressed the transcriptional activity of NRF2, the presence of BQ reduced this repressive activity. Co-immunoprecipitation confirmed that NCOR2 could bind to NRF2 and that this interaction was compromised by BQ overexpression, leading to increased transcriptional activity in NRF2. Our findings suggest BQ can regulate the NRF2 signaling pathway via interference with NCOR2 suppressive activity and reveals a novel role for BQ as a modulator of chemoresistance in breast cancer.

NecroX-5 alleviate lipopolysaccharide-induced acute respiratory distress syndrome by inhibiting TXNIP/NLRP3 and NF-κB.

The activation of NLRP3 inflammasome and NF-κB pathway, associating with oxidativestress, have been implicated in the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). NecroX-5 has been reported to exhibit theeffectsofanti-oxidation and anti-stress in various diseases. However, the role of NecroX-5 in ALI has not been explicitly demonstrated. The aim of this study was to explore the therapeutic effects and potential mechanism action of NecroX-5 on ALI. Here, we found that NecroX-5 pretreatment dramatically diminished the levels of IL-1ß, IL-18 and ROS in in RAW264.7 cells challenged with LPS and ATP. Furthermore, NecroX-5 suppressed the activation of NLRP3 inflammasome and NF-κB signalpathway. In addition, NecroX-5 also inhibited the thioredoxin-interacting protein (TXNIP) expression. In vivo, NecroX-5 reduced the LPS-induced lung histopathological injury, the number of TUNEL-positive cells, lung wet/dry (W/D) ratio, levels of total protein and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) in mice. Additionally, LPS-induced upregulation of myeloperoxidase (MPO), ROS production and malondialdehyde (MDA) were inhibited by NecroX-5 administration. Thus, our results demonstrate that NecroX-5 protects against LPS-induced ALI by inhibiting TXNIP/NLRP3 and NF-κB.

Enhanced recovery after cesarean delivery: a challenge for anesthesiologists.

Enhanced recovery after cesarean (ERAC) delivery is an evidence-based, multi-disciplinary approach throughout pre-, intra-, post-operative period. The ultimate goal of ERAC is to enhance recovery and improve the maternal and neonatal outcomes. This review highlights the role of anesthesiologist in ERAC protocols. This review provided a general introduction of ERAC including the purposes and the essential elements of ERAC protocols. The tool used for evaluating the quality of ERAC (ObsQoR-11) was discussed. The role of anesthesiologist in ERAC should cover the areas including management of peri-operative hypotension, prevention and treatment of intra- and post-operative nausea and vomiting, prevention of hypothermia and multi-modal peri-operative pain management, and active pre-operative management of unplanned conversion of labor analgesia to cesarean delivery anesthesia. Although some concerns still remain, ERAC implementation should not be delayed. Regular assessment and process improvement should be imbedded into the protocol. Further high-quality studies are warranted to demonstrate the effectiveness and efficacy of the ERAC protocol.

Intra-operative cell salvage for cesarean delivery: a retrospective study using propensity score matched analysis.

BACKGROUND: Obstetric hemorrhage is a major cause of maternal death during cesarean delivery. The objective of this retrospective observational study was to evaluate the efficacy and safety of intra-operative cell salvage (IOCS) in cesarean section. METHODS: We included a total of 361 patients diagnosed with central placenta previa who underwent cesarean section from May 2016 to December 2018. In this study, 196 patients received autologous transfusion using IOCS (IOCS group) and 165 patients accepted allogeneic blood transfusion (ABT group). Propensity score matched analysis was performed to balance differences in the baseline variables between the IOCS group and ABT group. Patients in the IOCS group were matched 1:1 to patients in the ABT group. RESULTS: After propensity score matching, 137 pairs of cases between the two groups were successfully matched and no significant differences in baseline characteristics were found between the IOCS group and ABT group. Patients in the IOCS group were associated with significantly shorter length of hospital stay, compared with ABT group (8.9 ±â€Š4.1 days vs. 10.3 ±â€Š5.2 days, t = -2.506, P = 0.013). The postoperative length of hospital stay was 5.3 ±â€Š1.4 days for patients in the IOCS group and 6.6 ±â€Š3.6 days for those in the ABT group (t = -4.056, P < 0.001). The post-operative hemoglobin level in the IOCS group and ABT group was 101.3 ±â€Š15.4 and 96.3 ±â€Š16.6 g/L, respectively, which were significantly different (t = 2.615, P = 0.009). Allogeneic red blood cell transfusion was significantly lower at 0 unit (range: 0-11.5 units) in the IOCS group when compared with 2 units (range: 1-20 units) in the ABT group (P < 0.001). CONCLUSIONS: This retrospective observational study using propensity score matched analysis suggested that IOCS was associated with shorter length of postoperative hospital stay and higher post-operative hemoglobin levels during cesarean delivery.

Study on Isomeric Impurities in Cefotiam Hydrochloride.

In this study, two isomeric impurities were identified in cefotiam hydrochloride injection preparation and were characterized. Column-switching HPLC-MS and NMR techniques were used to identify the impurity 1 as the Δ3(4) isomers of cefotiam. Using software-based calculations, it was predicted that neither of the isomeric impurities was embryotoxic. This study provides a reference for the production, storage, and quality control of cefotiam and related cephalosporin antibiotics.