Blood Neutrophil-to-Lymphocyte Ratio as a Potential Prognostic Marker in Dogs ≤10 kg With Multicentric Lymphoma.

Canine lymphoma, the most prevalent haematopoietic tumour in dogs, presents significant challenges in veterinary oncology. This study investigates the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in small-sized dogs (≤10 kg) with multicentric lymphoma. In this retrospective study, we examined medical records and haematological data from 35 dogs to assess the association between NLR and two key outcomes: time-to-progression (TTP) and lymphoma-specific survival (LSS) using Cox proportional hazards models. Our findings revealed a significant correlation between elevated NLR and a worse prognosis, as evidenced by TTP (p = 0.005) and LSS (p = 0.001). NLR is linked to increased hazard ratios (HRs) for the time-to-progression rate (TTPR) at 180, 360 and 540 days (p = 0.001, p = 0.003 and p = 0.005, respectively) and the lymphoma-specific survival rate (LSSR) at the same intervals (p = 0.016, p = 0.001 and p = 0.001, respectively). Cutoff value of 3.764 for NLR was established, above which there is a significantly increased risk of early disease progression and decreased survival. Additionally, our analysis indicates that dogs with substage b exhibited earlier progression than those with substage a, evident in overall (p = 0.026) and TTPR at 180 days (p = 0.004), 360 days (p = 0.018), 540 days (p = 0.026) and LSSR at 180 days (p = 0.033). The results underscore the potential of NLR as a prognostic marker in cases of dogs ≤10 kg with multicentric lymphoma, suggesting that higher NLR is associated with a poorer prognosis.

Arthroscopic Treatment of Femoroacetabular Impingement Syndrome: An Updated Review.

Treatment strategies for femoroacetabular impingement (FAI) syndrome have evolved in tandem with increased comprehension of FAI's impact on hip joint health. Early intervention, including arthroscopic surgery, has gained popularity due to its potential to delay the progression of osteoarthritis. Arthroscopic surgery has demonstrated significant efficacy in treating FAI syndrome, with robust evidence from randomized controlled trials and systematic reviews supporting its use. Despite arthroscopic surgery's success, complications and reoperations are not uncommon. The incidence ranges from 1% to 31% and 4% to 13%, respectively. Adjunctive biologic treatments, such as bone marrow aspirate concentrates and platelet-rich plasma, have shown promise in chondral lesion management. However, robust evidence supporting their routine use in FAI syndrome is currently lacking. Among conservative treatment methods, intra-articular injections offer diagnostic and therapeutic benefits for FAI patients. While they may provide pain relief and aid in prognosis, their long-term efficacy remains a subject of debate. Comparative studies between conservative and arthroscopic treatments highlight the importance of personalized approaches in managing FAI syndrome. In conclusion, recent advancements in FAI syndrome management have illuminated various treatment modalities. Arthroscopic surgery stands as a pivotal intervention, offering substantial benefits in pain relief, function, and quality of life. However, careful patient selection and postoperative monitoring are crucial for optimizing outcomes. Adjunctive biologics and intra-articular injections show promise but require further investigation. Tailoring treatment to individual patient characteristics remains paramount in optimizing FAI syndrome management.

Decreased Sirtuin 4 Levels Promote Cellular Proliferation and Invasion in Papillary Thyroid Carcinoma.

OBJECTIVE: This study examined the effect of Sirtuin 4 (Sirt4), a NAD+-dependent deacetylase, on the proliferation and progression of papillary thyroid carcinoma (PTC). METHODS: Data from The Cancer Genome Atlas (TCGA) were analyzed to identify Sirt4 expression in thyroid cancer. Subsequently, the correlation between Sirt4 expression and clinical characteristics was examined in 205 PTC tissue samples. In vitro assays using three human thyroid cancer cell lines (B-CPAP, TPC-1, and SNU-790) were conducted to assess the effects of regulated Sirt4 expression on cell growth, apoptosis, invasion, and migration. Furthermore, in vivo experiments were performed in a xenograft mouse model. RESULTS: GEO and TCGA data indicated that Sirt4 expression is lower in thyroid cancer and Sirt4 downregulation is associated with poor overall survival. In our PTC tissues, positive Sirt4 expression was associated with decreased extracapsular extension. In in vitro experiments using three human thyroid cancer cell lines, overexpression of Sirt4 decreased cell survival, clonogenic potential, and invasion and migratory capabilities, as well as inducing apoptosis and increasing reactive oxygen species levels. Sirt4 overexpression upregulated E-cadherin and downregulated N-cadherin, suggesting its potential involvement in the regulation of epithelial-mesenchymal transition. These findings were confirmed in vivo using a xenograft mouse model. CONCLUSION: This study provides novel insight into the potential contribution of Sirt4 to regulation of the pathological progression of PTC. The data suggest that Sirt4 plays a tumor-suppressive role in PTC by inhibiting growth, survival, and invasive potential. Future research should investigate the molecular mechanisms underlying these effects of Sirt4.

Oxygen reserve index versus conventional peripheral oxygen saturation for prevention of hypoxaemia: A randomised controlled trial.

BACKGROUND: Hypoxaemia occurs frequently during paediatric laryngeal microsurgery. OBJECTIVE: The oxygen reserve index is a noninvasive and continuous parameter to assess PaO2 levels in the range of 100 to 200 mmHg. It ranges from 0 to 1.0. We investigated whether monitoring the oxygen reserve index can reduce the incidence of SpO2 90% or less. DESIGN: Randomised controlled trial. SETTING: A tertiary care paediatric hospital. PARTICIPANTS: Paediatric patients aged 18 years or less scheduled to undergo laryngeal microsurgery. INTERVENTION: The patients were randomly allocated to the oxygen reserve index or control groups, and stratified based on the presence of a tracheostomy tube. Rescue intervention was performed when the oxygen reserve index was 0.2 or less and the SpO2 was 94% or less in the oxygen reserve index and control groups, respectively. MAIN OUTCOME MEASURE: The primary outcome was the incidence of SpO2 90% or less during the surgery. RESULTS: Data from 88 patients were analysed. The incidence of SpO2 ≤ 90% did not differ between the oxygen reserve index and control groups [P = 0.114; 11/44, 25% vs. 18/44, 40.9%; relative risk: 1.27; and 95% confidence interval (CI): 0.94 to 1.72]. Among the 128 rescue interventions, SpO2 ≤ 90% event developed in 18 out of 75 events (24%) and 42 out of 53 events (79.2%) in the oxygen reserve index and control groups, respectively (P < 0.001; difference: 55.2%; and 95% CI 38.5 to 67.2%). The number of SpO2 ≤ 90% events per patient in the oxygen reserve index group (median 0, maximum 3) was less than that in the control group (median 0, maximum 8, P = 0.031). CONCLUSION: Additional monitoring of the oxygen reserve index, with a target value of greater than 0.2 during paediatric airway surgery, alongside peripheral oxygen saturation, did not reduce the incidence of SpO2 ≤ 90%.

Effectiveness of a novel artificial intelligence-assisted colonoscopy system for adenoma detection: a prospective, propensity score-matched, non-randomized controlled study in Korea.

Background/Aims: The real-world effectiveness of computer-aided detection (CADe) systems during colonoscopies remains uncertain. We assessed the effectiveness of the novel CADe system, ENdoscopy as AI-powered Device (ENAD), in enhancing the adenoma detection rate (ADR) and other quality indicators in real-world clinical practice. Methods: We enrolled patients who underwent elective colonoscopies between May 2022 and October 2022 at a tertiary healthcare center. Standard colonoscopy (SC) was compared to ENAD-assisted colonoscopy. Eight experienced endoscopists performed the procedures in randomly assigned CADe- and non-CADe-assisted rooms. The primary outcome was a comparison of ADR between the ENAD and SC groups. Results: A total of 1,758 sex- and age-matched patients were included and evenly distributed into two groups. The ENAD group had a significantly higher ADR (45.1% vs. 38.8%, p=0.010), higher sessile serrated lesion detection rate (SSLDR) (5.7% vs. 2.5%, p=0.001), higher mean number of adenomas per colonoscopy (APC) (0.78±1.17 vs. 0.61±0.99; incidence risk ratio, 1.27; 95% confidence interval, 1.13-1.42), and longer withdrawal time (9.0±3.4 vs. 8.3±3.1, p<0.001) than the SC group. However, the mean withdrawal times were not significantly different between the two groups in cases where no polyps were detected (6.9±1.7 vs. 6.7±1.7, p=0.058). Conclusions: ENAD-assisted colonoscopy significantly improved the ADR, APC, and SSLDR in real-world clinical practice, particularly for smaller and nonpolypoid adenomas.

What features of stem increase the risk of intraoperative femoral fracture during cementless primary hip arthroplasty?

INTRODUCTION: Cementless fixation has become increasingly popular in hip arthroplasty due to its shorter operation time, easier technique, biologic fixation, and avoidance of bone cement implantation syndrome compared to cemented fixation. However, intraoperative periprosthetic femoral fracture (IOPFx) is a disconcerting complication during cementless hip arthroplasty. Our purpose was to identify the features of cementless stem that increase the risk of IOPFx during primary hip arthroplasty. MATERIALS AND METHODS: We retrospectively reviewed all 4806 hip arthroplasties that was performed in a single institution from May 2003 to December 2020. Age at the index arthroplasty, sex, body mass index, physical status, ambulatory function, side of the operation, operational history, cause of the index arthroplasty, type of arthroplasty, surgical approach, surgeon, implant information, and events during the operation were investigated. The shoulder geometry and length of stem were also reviewed. The event of interest was narrowed down to IOPFx among various records of intraoperative events. RESULTS: We found IOPFx of 2.6% among all the hips operated with cementless stem. In the multivariable analysis, female (OR = 1.52), childhood hip disease (OR = 2.30), stove-pipe femur (OR = 2.43), combined approach (OR = 2.60), and standard length of stem (OR = 1.59) were found to be significant risk factors of IOPFx. CONCLUSIONS: In conclusion, a stem with a standard length is significantly associated with risk of IOPFx compared to a shortened stem. These findings highlight the importance of careful consideration in terms of the risk of IOPFx when standard length cementless stem is chosen.

An eight-year retrospective study on the clinical outcomes of laser surface-treated implants.

PURPOSE: To retrospectively evaluate peri-implant bone loss and health status associated with the long-term use of laser surface-treated implants. METHODS: For control study, total of 23 titanium ASTM F136 grade 23 implants were placed in the edentulous molar area of the mandible. When the Implant Stability Quotient (ISQ) ≥ 70 and insertion torque value (ITV) ≥ 35-50 Ncm at the insertion site, an immediate provisional restoration was connected to the implant within a week after surgery. The definitive restorations were placed 2 months after surgery for all implants. 13 implants were immediately loaded, while 10 implants were conventionally loaded. For comparative study, Radiographs were taken from third years for and then annually for the subsequent eight years to monitor marginal bone loss. RESULTS: After eight year of implant installation, the average change in vertical bone loss was 0.009 mm (P < 0.001), while the average change in horizontal bone loss 8 year after implant placement was 0.026 mm (P < 0.001). The mean marginal bone loss was < 0.2 mm on average. CONCLUSIONS: In this retrospective study, laser-treated implants exhibit a low rate of bone absorption around the implants.

Nevus Spilus, Partial Unilateral Lentiginosis, and Linear and Whorled Nevoid Hypermelanosis: A Comparison of Clinical Features, Course, and Treatment Response.

Skin diseases manifesting as agminated pigmented lesions have overlapping clinical manifestations. Therefore, accurate differentiation is challenging. The clinical characteristics, histopathological findings, and treatment response of patients diagnosed with partial unilateral lentiginosis, nevus spilus, or linear and whorled nevoid hypermelanosis were retrospectively analysed. Each disease demonstrated distinct demographic and clinical characteristics, and the responses to laser treatment varied. The median age at onset varied significantly among the groups: 0.1, 6.6, and 0.5 years in patients with nevus spilus, partial unilateral lentiginosis, and linear and whorled nevoid hypermelanosis, respectively. Regarding the locations of the skin lesions, partial unilateral lentiginosis occurred predominantly on the head and neck, while approximately half of nevus spilus and linear and whorled nevoid hypermelanosis were observed on the extremities. Although linear and whorled nevoid hypermelanosis and partial unilateral lentiginosis share a similar histological feature of basal hyperpigmentation, patients with linear and whorled nevoid hypermelanosis showed the best response to laser treatment, while patients with partial unilateral lentiginosis demonstrated a poor treatment response. The study's data may provide important clues for the differential diagnosis and clinical decision-making regarding the treatment of these agminated pigmented lesions.

Optimizing pain management in breast cancer care: Utilizing 'All of Us' data and deep learning to identify patients at elevated risk for chronic pain.

PURPOSE: The aim of the study was to develop a prediction model using deep learning approach to identify breast cancer patients at high risk for chronic pain. DESIGN: This study was a retrospective, observational study. METHODS: We used demographic, diagnosis, and social survey data from the NIH 'All of Us' program and used a deep learning approach, specifically a Transformer-based time-series classifier, to develop and evaluate our prediction model. RESULTS: The final dataset included 1131 patients. We evaluated the deep learning prediction model, which achieved an accuracy of 72.8% and an area under the receiver operating characteristic curve of 82.0%, demonstrating high performance. CONCLUSION: Our research represents a significant advancement in predicting chronic pain among breast cancer patients, leveraging deep learning model. Our unique approach integrates both time-series and static data for a more comprehensive understanding of patient outcomes. CLINICAL RELEVANCE: Our study could enhance early identification and personalized management of chronic pain in breast cancer patients using a deep learning-based prediction model, reducing pain burden and improving outcomes.

Risk factors for chloral hydrate sedation failure in pediatric patients: a retrospective analysis.

Background: This study aimed to investigate the risk factors for chloral hydrate sedation failure and complications in a tertiary children's hospital in South Korea. Methods: A retrospective analysis of pediatric procedural sedation with chloral hydrate between January 1, 2021, and March 30, 2022, was performed. The collected data included patient characteristics, sedation history, and procedure. Multivariable regression analysis was performed to identify the risk factors for procedural sedation failure and complications. Results: A total of 6691 procedural sedation were included in the analysis; sedation failure following chloral hydrate (50 mg/kg) occurred in 1457 patients (21.8%) and was associated with a higher rate of overall complications compared to those with successful sedation (17.5% [225 / 1457] vs. 6.2% [322 / 5234]; P < 0.001; odds ratio, 3.236). In the multivariable regression analysis, the following factors were associated with increased risk of sedation failure: general ward or intensive care unit inpatient (compared with outpatient); congenital syndrome; oxygen dependency; history of sedation failure or complications with chloral hydrate; procedure more than 60 min; and magnetic resonance imaging, radiotherapy, or procedures with painful or intense stimuli (all P values < 0.05). Factors contributing to the complications included general ward inpatient, congenital syndromes, congenital heart disease, preterm birth, oxygen dependency, history of complications with chloral hydrate, and current sedation failure with chloral hydrate (all P values < 0.05). Conclusions: To achieve successful sedation with chloral hydrate, the patient's sedation history, risk factors, and the type and duration of the procedure should be considered.

Highly functional duodenal stent with photosensitizers enables photodynamic therapy for metabolic syndrome treatment: Feasibility and safety study in a porcine model.

Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS.

The Current Incidence and Future Projection of Acetabular Fractures in Korea.

BACKGROUND: As one of the most challenging fractures to orthopedic surgeons, acetabular fractures show a wide range of incidence among countries and regions with even more variance in the treatment modalities. In this study, we aimed to investigate the epidemiology of acetabular fractures, and to compare the rate of subsequent total hip arthroplasty (THA) between nonoperative and operative treatments in South Korea using a medical claims database. METHODS: This was a retrospective study using the Korean Health Insurance Review and Assessment database. Patients admitted for acetabular fractures from January 2007 to December 2018 were identified using International Classification of Diseases-10 codes. Kaplan-Meier survival analysis was used to compare the cumulative incidence of THA between two groups. We also evaluated the survivorship of operative group according to the type of institutions. RESULTS: The incidence rate of acetabular fractures increased by 28% between 2007 and 2018. Acetabular fractures were more common in men (62%) than women (38%), and most common in the patients older than 80 years. The number of acetabular fractures was estimated to increase 1.7-fold in 2030 compared to 2018. Operative treatment accounted for 16% of cases, and nonoperative treatment for 84%. The incidence of subsequent THA was higher in the operative treatment group than in the nonoperative group (P < 0.001). The higher rate in the operative treatment group is probably related with the severity of the fracture type. The rate of subsequent THA was higher in patients who initially treated in general hospitals compared with those who were initially treated in tertiary hospitals. CONCLUSION: The incidence of acetabular fractures is increasing in South Korea, in line with global trends. Most acetabular fractures are treated conservatively, and those who receive surgery are more likely to require a subsequent THA. Patients who were operated in general hospitals had highest possibility of subsequent THA after acetabular fractures.

Advancing equity in breast cancer care: natural language processing for analysing treatment outcomes in under-represented populations.

OBJECTIVE: The study aimed to develop natural language processing (NLP) algorithms to automate extracting patient-centred breast cancer treatment outcomes from clinical notes in electronic health records (EHRs), particularly for women from under-represented populations. METHODS: The study used clinical notes from 2010 to 2021 from a tertiary hospital in the USA. The notes were processed through various NLP techniques, including vectorisation methods (term frequency-inverse document frequency (TF-IDF), Word2Vec, Doc2Vec) and classification models (support vector classification, K-nearest neighbours (KNN), random forest (RF)). Feature selection and optimisation through random search and fivefold cross-validation were also conducted. RESULTS: The study annotated 100 out of 1000 clinical notes, using 970 notes to build the text corpus. TF-IDF and Doc2Vec combined with RF showed the highest performance, while Word2Vec was less effective. RF classifier demonstrated the best performance, although with lower recall rates, suggesting more false negatives. KNN showed lower recall due to its sensitivity to data noise. DISCUSSION: The study highlights the significance of using NLP in analysing clinical notes to understand breast cancer treatment outcomes in under-represented populations. The TF-IDF and Doc2Vec models were more effective in capturing relevant information than Word2Vec. The study observed lower recall rates in RF models, attributed to the dataset's imbalanced nature and the complexity of clinical notes. CONCLUSION: The study developed high-performing NLP pipeline to capture treatment outcomes for breast cancer in under-represented populations, demonstrating the importance of document-level vectorisation and ensemble methods in clinical notes analysis. The findings provide insights for more equitable healthcare strategies and show the potential for broader NLP applications in clinical settings.

Anti-inflammatory and antioxidant mechanisms of coniferaldehyde in lipopolysaccharide-induced neuroinflammation: Involvement of AMPK/Nrf2 and TAK1/MAPK/NF-κB signaling pathways.

Microglia are primarily involved in inflammatory reactions and oxidative stress in the brain; as such reducing microglial activation has been proposed as a potential therapeutic strategy for neurodegenerative disorders. Herein, we investigated the anti-inflammatory and antioxidant activities of coniferaldehyde (CFA), a naturally occurring cinnamaldehyde derivative, on activated microglia to evaluate its therapeutic potential. CFA inhibited the production of nitric oxide (NO) and proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6, in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. CFA also inhibited intracellular reactive oxygen species levels and oxidative stress markers such as 4-HNE and 8-OHdG. Detailed mechanistic studies showed that CFA exerted anti-inflammatory effects by inhibiting TAK1-mediated MAP kinase/NF-κB activation and upregulating AMPK signaling pathways. In addition, CFA exerted antioxidant effects by inhibiting the NADPH oxidase subunits and by increasing the expression of antioxidant enzymes such as HO-1, NQO1, and catalase by upregulating Nrf2 signaling. Finally, we confirmed the effects of CFA on the brains of the LPS-injected mice. CFA inhibited microglial activation and the expression of proinflammatory markers and increased Nrf2-driven antioxidant enzymes. Furthermore, CFA inhibited the production of 4-HNE and 8-OHdG in the brains of LPS-injected mice. As a result, CFA's significant anti-inflammatory and antioxidant properties may have therapeutic applications in neuroinflammatory disorders related with oxidative stress and microglial activation.

Effects of goal-directed analgesia using the analgesia nociception index in children undergoing surgery for moyamoya disease: A randomised controlled trial.

BACKGROUND: The potential benefits of Analgesia Nociception Index guided intra-operative analgesia on intra-operative opioid consumption remains to be demonstrated in paediatric anaesthesia. OBJECTIVES: This study aimed to explore the effects of Analgesia Nociception Index guided analgesia on sufentanil consumption during anaesthesia and postoperative pain scores in paediatric patients with moyamoya disease. DESIGN: A prospective randomised controlled study. SETTING: Seoul National University Children's Hospital, Seoul, Republic of Korea. PATIENTS: A total of 40 children scheduled for encephaloduroarteriosynangiosis. MAIN OUTCOME MEASURES: The primary outcome was total intra-operative sufentanil consumption, and the secondary outcomes included postoperative pain scores and incidence of opioid-related adverse events. RESULTS: The Analgesia Nociception Index group showed lower intra-operative sufentanil consumption (in µg kg -1  h -1 ) compared with the Standard group (0.30 ±â€Š0.12 and 0.39 ±â€Š0.17, respectively; mean difference, -0.09; 95% confidence interval, -0.19 to 0.00; P  = 0.049). Postoperatively, compared with the Standard group, the Analgesia Nociception Index group reported lower median pain scores at 18 and 24 h and maximum pain within 24 h (1 [0 to 2] vs. 3 [2 to 5]; P  = 0.004, 1 [0 to 2] vs. 3 [1 to 4]; P  = 0.041, and 4 [3 to 5] vs. 5 [4 to 7]; P  = 0.045, respectively), with fewer patients experiencing nausea (3 [15%] vs. 10 [50%], P  = 0.043). CONCLUSION: The Analgesia Nociception Index guided analgesic protocol can reduce intra-operative sufentanil consumption and postoperative pain within 24 h with fewer nausea symptoms in paediatric patients with moyamoya disease who undergo encephaloduroarteriosynangiosis. TRIAL REGISTRATION NUMBER: NCT05672212.

Atmospheric particulate matter and hypoxaemia in Korean children receiving general anaesthesia: A retrospective analysis.

BACKGROUND: The association between the concentration of atmospheric particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia in children receiving general anaesthesia is unclear. OBJECTIVE: To investigate the association between the exposure to particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% for more than 1 min, in children. DESIGN: Retrospective study. SETTING: Single-centre. PARTICIPANTS: Children aged 18 years or younger who received general anaesthesia between January 2019 and October 2020. INTERVENTION: Information on daily levels of particulate matter with a diameter 10 µm or less and 2.5 µm or less measured within a neighbourhood corresponding to the area defined by the hospital's zip code was obtained from publicly available air-quality data. MAIN OUTCOME MEASURES: The primary outcome was intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% lasting for more than 1 min, manually verified by anaesthesiologists using vital sign registry data extracted at 2 s intervals. RESULTS: Of the patients finally analysed, 3.85% (489/13 175) experienced intra-operative hypoxaemia. Higher levels of particulate matter 10 µm or less in diameter (≥81 µg m -3 , 17/275, 6.2%) were associated with an increased occurrence of intra-operative hypoxaemia compared with lower particulate matter concentrations [<81 µg m -3 , 472/12 900, 3.7%; adjusted odds ratio, 1.71; 95% confidence interval (CI), 1.04 to 2.83; P  = 0.035]. CONCLUSION: The level of particulate matter on the day of surgery pose a risk of intra-operative hypoxaemia in children receiving general anaesthesia. If the concentrations of particulate matter 10 µm or less in diameter on the day of surgery are high, children receiving general anaesthesia should be managed with increased caution.

Light-Triggered PROTAC Nanoassemblies for Photodynamic IDO Proteolysis in Cancer Immunotherapy.

While proteolysis-targeting chimeras (PROTACs) hold great potential for persistently reprogramming the immunosuppressive tumor microenvironment via targeted protein degradation, precisely activating them in tumor tissues and preventing uncontrolled proteolysis at off-target sites remain challenging. Herein, a light-triggered PROTAC nanoassembly (LPN) for photodynamic indoleamine 2,3-dioxygenase (IDO) proteolysis is reported. The LPN is derived from the self-assembly of prodrug conjugates, which comprise a PROTAC, cathepsin B-specific cleavable peptide linker, and photosensitizer, without any additional carrier materials. In colon tumor models, intravenously injected LPNs initially silence the activity of PROTACs and accumulate significantly in targeted tumor tissues due to an enhanced permeability and retention effect. Subsequently, the cancer biomarker cathepsin B begins to trigger the release of active PROTACs from the LPNs through enzymatic cleavage of the linkers. Upon light irradiation, tumor cells undergo immunogenic cell death induced by photodynamic therapy to promote the activation of effector T cells, while the continuous IDO degradation of PROTAC simultaneously blocks tryptophan metabolite-regulated regulatory-T-cell-mediated immunosuppression. Such LPN-mediated combinatorial photodynamic IDO proteolysis effectively inhibits tumor growth, metastasis, and recurrence. Collectively, this study presents a promising nanomedicine, designed to synergize PROTACs with other immunotherapeutic modalities, for more effective and safer cancer immunotherapy.

Posterior Approach and Inferior Capsulotomy in Bipolar Hemiarthroplasty for Femoral Neck Fractures: Comparison with Superior Capsulotomy.

Background: Hemiarthroplasty is frequently used to treat displaced femoral neck fractures in elderly patients, but it has a higher risk of postoperative dislocation. We introduced the posterior approach and inferior capsulotomy (PAICO) to enhance joint stability after bipolar hemiarthroplasty for femoral neck fracture. We evaluated whether the PAICO would have a lower dislocation rate than the conventional posterior approach with superior capsulotomy. Methods: From January 2021 to December 2021, we prospectively recruited 25 patients (25 hips) aged 50 years or older who underwent bipolar hemiarthroplasty for femoral neck fractures due to low-energy trauma as the PAICO group. We compared the PAICO group with a historical control group who had undergone hemiarthroplasty in 7 institutes between 2010 and 2020. The primary endpoint was dislocation within 1 year after the surgery. We compared data from the PAICO group with the data from the historical control group from the Korean Hip Fracture Registry which was carried out in South Korea. Results: A total of 25 patients (25 hips) were enrolled in the present study; 3,477 patients (3,571 hips) who underwent bipolar hemiarthroplasty were reviewed as the historical control group. In the PAICO group, we observed no dislocation, whereas the dislocation rate in the control group was 1.3%. Conclusions: In patients with displaced femoral neck fractures, the PAICO approach demonstrated comparable results in operation time and complication rates when compared to bipolar hemiarthroplasty using superior capsulotomy. Notably, there were no observed cases of dislocation among patients who underwent the PAICO approach. We recommend this PAICO approach to surgeons using the posterior approach, hoping to prevent dislocation in bipolar hemiarthroplasty.

Ventriculoperitoneal shunt infection and malfunction in adult patients: incidence, risk factors, and long-term follow-up of single institution experience.

Ventriculoperitoneal shunt surgery was developed to manage excessive cerebrospinal fluid (CSF) in the brain's ventricles and is considered a mainstream treatment. Despite the development of the shunt device system, various complications still occur. In this study, we reported 307 cases and a long-term follow-up of at least five years of adult patients who underwent VP shunt surgery and analyzed various factors that may affect revision surgery. A retrospective study was conducted at Asan Medical Center, Korea, a tertiary medical center. We reviewed 307 cases from January 2012 to December 2018. The patients' neurological status, predisposing medical conditions, laboratory findings, and other operation-related factors were reviewed using electrical medical records. The normal function group comprised 272 cases (88.6%), and the overall incidence of revision group comprised 35 cases (11.4%). Of the 35 revision surgery cases, 30 (85.71%) were due to shunt malfunctions, such as obstruction, overdrainage, and valve-related errors while 5 (14.29%) were due to shunt infection. Patient demographics, mental status, and operation time did not influence revision as risk factors. Serum laboratory findings showed no statistical difference between the two groups. The white blood cell (WBC) count in the CSF profile differed significantly between the two groups. The Hakim Programmable valve (Codman, USA) is mainly used in our center. In addition, various shunt systems were used, including Strata Regulatory valve (Medtronic, USA), proGAV (Aesculap, USA), and Accu-Flo (Codman, USA). This study analyzed the factors affecting long-term outcomes. Based on these findings, efforts are needed to achieve more favorable outcomes in the future.

The role of PCSK9 in glomerular lipid accumulation and renal injury in diabetic kidney disease.

AIMS/HYPOTHESIS: Glomerular lipid accumulation is a defining feature of diabetic kidney disease (DKD); however, the precise underlying mechanism requires further elucidation. Recent evidence suggests a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in intracellular lipid homeostasis. Although PCSK9 is present in kidneys, its role within kidney cells and relevance to renal diseases remain largely unexplored. Therefore, we investigated the role of intracellular PCSK9 in regulating lipid accumulation and homeostasis in the glomeruli and podocytes under diabetic conditions. Furthermore, we aimed to identify the pathophysiological mechanisms responsible for the podocyte injury that is associated with intracellular PCSK9-induced lipid accumulation in DKD. METHODS: In this study, glomeruli were isolated from human kidney biopsy tissues, and glomerular gene-expression analysis was performed. Also, db/db and db/m mice were used to perform glomerular gene-expression profiling. We generated DKD models using a high-fat diet and low-dose intraperitoneal streptozocin injection in C57BL/6 and Pcsk9 knockout (KO) mice. We analysed cholesterol and triacylglycerol levels within the kidney cortex. Lipid droplets were evaluated using BODIPY staining. We induced upregulation and downregulation of PCSK9 expression in conditionally immortalised mouse podocytes using lentivirus and siRNA transfection techniques, respectively, under diabetic conditions. RESULTS: A significant reduction in transcription level of PCSK9 was observed in glomeruli of individuals with DKD. PCSK9 expression was also reduced in podocytes of animals under diabetic conditions. We observed significantly higher lipid accumulation in kidney tissues of Pcsk9 KO DKD mice compared with wild-type (WT) DKD mice. Additionally, Pcsk9 KO mouse models of DKD exhibited a significant reduction in mitochondria number vs WT models, coupled with a significant increase in mitochondrial size. Moreover, albuminuria and podocyte foot process effacement were observed in WT and Pcsk9 KO DKD mice, with KO DKD mice displaying more pronounced manifestations. Immortalised mouse podocytes exposed to diabetic stimuli exhibited heightened intracellular lipid accumulation, mitochondrial injury and apoptosis, which were ameliorated by Pcsk9 overexpression and aggravated by Pcsk9 knockdown in mouse podocytes. CONCLUSIONS/INTERPRETATION: The downregulation of PCSK9 in podocytes is associated with lipid accumulation, which leads to mitochondrial dysfunction, cell apoptosis and renal injury. This study sheds new light on the potential involvement of PCSK9 in the pathophysiology of glomerular lipid accumulation and podocyte injury in DKD.