Obesity exacerbates ischemia-reperfusion injury and senescence in murine kidneys and perirenal adipose tissues.

Background: Obesity is a major worldwide health problem and can be related to cellular senescence. Along with the rise in obesity, the comorbidity of renal ischemia-reperfusion (IR) injury is increasing. Whether obesity accelerates the severity of IR injury and whether senescence contributes to these conditions remain unclear. We studied the degree of injury and cellular senescence in the IR kidneys and perirenal adipose tissues of high-fat-diet-induced obese mice. Methods: C57BL/6 mice fed standard chow or a high-fat diet for 16 weeks were randomized to renal IR or sham group (n = 6-10 each). Renal IR was performed by unilateral clamping of the right renal pedicle for 30 minutes. Six weeks after surgery, renal function, perirenal fat/renal senescence, and histology were evaluated ex vivo. Results: Obese mice showed more renal tubular damage and fibrosis in IR injury than control mice, even though the degree of ischemic insult was comparable. Renal expression of senescence and its secretory phenotype was upregulated in either IR injury or with a high-fat diet and was further increased in the IR kidneys of obese mice. Fat senescence and the expression of tumor necrosis factor alpha were also increased, especially in the perirenal depot of the IR kidneys, with a high-fat diet. Conclusion: A high-fat diet aggravates IR injury in murine kidneys, which is associated, at least in part, with perirenal fat senescence and inflammation. These observations support the exploration of therapeutic targets of the adipo-renal axis in injured obese kidneys.

Association between Gout and Gastric Cancer: A Nested Case-Control Study Using a National Health Sample Cohort.

Given the global significance of gout and gastric cancer (GC) as major health problems with interrelated impacts, we examined the development of GC in Korean patients with gout. We conducted a nested case-control study using data from 10,174 GC patients and 40,696 control patients from the Korean National Health Insurance Service-National Sample Cohort database. Propensity score matching (1:4) with propensity score overlap-weighted adjustment was used to reduce selection bias and estimate the odds ratio (OR) and 95% confidence intervals (CIs) for the association between gout and GC. An adjusted OR for GC was not significantly higher in patients with gout than in control patients (1.02; 95% CI, 0.93-1.12; p = 0.652). Additionally, no association between gout and GC was observed in subgroup analyses such as sex, age, level of income, region of residence, or Charlson Comorbidity Index score. In conclusion, these results suggest that gout is not a significant independent risk factor for GC among the Korean population. Additional investigation is required to establish a causal association between gout and GC, and to generalize these results to general populations.

Combined DNA Methylation and Gastric Microbiome Marker Predicts Helicobacter pylori-Negative Gastric Cancer.

Background/Aims: While DNA methylation and gastric microbiome are each associated with gastric cancer (GC), their combined role in predicting GC remains unclear. This study investigated the potential of a combined DNA methylation and gastric microbiome signature to predict Helicobacter pylori-negative GC. Methods: In this case-control study, we conducted quantitative methylation-specific polymerase chain reaction to measure the methylation levels of DKK3, SFRP1, EMX1, NKX6-1, MIR124-3, and TWIST1 in the gastric mucosa from 75 H. pylori-negative patients, including chronic gastritis (CG), intestinal metaplasia (IM), and GC. A combined analysis of DNA methylation and gastric microbiome, using 16S rRNA gene sequencing, was performed in 30 of 75 patients. Results: The methylation levels of DKK3, SFRP1, EMX1, MIR124-3, and TWIST1 were significantly higher in patients with GC than in controls (all q<0.05). MIR124-3 and TWIST1 methylation levels were higher in patients with IM than those with CG and also in those with GC than in those with IM (all q<0.05). A higher methylation level of TWIST1 was an independent predictor for H. pylori-negative GC after adjusting for age, sex, and atrophy (odds ratio [OR], 15.15; 95% confidence interval [CI], 1.58 to 145.46; p=0.018). The combination of TWIST1 methylation and GC microbiome index (a microbiome marker) was significantly associated with H. pylori-negative GC after adjusting for age, sex, and atrophy (OR, 50.00; 95% CI, 1.69 to 1,476; p=0.024). Conclusions: The combination of TWIST1 methylation and GC microbiome index may offer potential as a biomarker for predicting H. pylori-negative GC.

The mechanism underlying correlation of particulate matter-induced ferroptosis with inflammasome activation and iron accumulation in macrophages.

Particulate matter (PM) is a global environmental hazard, which affects human health through free radical production, cell death induction, and immune responses. PM activates inflammasomes leading to excessive inflammatory responses and induces ferroptosis, a type of cell death. Despite ongoing research on the correlation among PM-induced ferroptosis, immune response, and inflammasomes, the underlying mechanism of this relationship has not been elucidated. In this study, we demonstrated the levels of PM-induced cell death and immune responses in murine macrophages, J774A.1 and RAW264.7, depending on the size and composition of particulate matter. PM2.5, with extraction ions, induced significant levels of cell death and immune responses; it induces lipid peroxidation, iron accumulation, and reactive oxygen species (ROS) production, which characterize ferroptosis. In addition, inflammasome-mediated cell death occurred owing to the excessive activation of inflammatory responses. PM-induced iron accumulation activates ferroptosis and inflammasome formation through ROS production; similar results were observed in vivo. These results suggest that the link between ferroptosis and inflammasome formation induced by PM, especially PM2.5 with extraction ions, is established through the iron-ROS axis. Moreover, this study can effectively facilitate the development of a new therapeutic strategy for PM-induced immune and respiratory diseases.

Performance reporting design in artificial intelligence studies using image-based TNM staging and prognostic parameters in rectal cancer: a systematic review.

PURPOSE: The integration of artificial intelligence (AI) and magnetic resonance imaging in rectal cancer has the potential to enhance diagnostic accuracy by identifying subtle patterns and aiding tumor delineation and lymph node assessment. According to our systematic review focusing on convolutional neural networks, AI-driven tumor staging and the prediction of treatment response facilitate tailored treat-ment strategies for patients with rectal cancer. METHODS: This paper summarizes the current landscape of AI in the imaging field of rectal cancer, emphasizing the performance reporting design based on the quality of the dataset, model performance, and external validation. RESULTS: AI-driven tumor segmentation has demonstrated promising results using various convolutional neural network models. AI-based predictions of staging and treatment response have exhibited potential as auxiliary tools for personalized treatment strategies. Some studies have indicated superior performance than conventional models in predicting microsatellite instability and KRAS status, offer-ing noninvasive and cost-effective alternatives for identifying genetic mutations. CONCLUSION: Image-based AI studies for rectal can-cer have shown acceptable diagnostic performance but face several challenges, including limited dataset sizes with standardized data, the need for multicenter studies, and the absence of oncologic relevance and external validation for clinical implantation. Overcoming these pitfalls and hurdles is essential for the feasible integration of AI models in clinical settings for rectal cancer, warranting further research.

Dietary intake is associated with the prevalence of uterine leiomyoma in Korean women: A retrospective cohort study.

OBJECTIVE: Uterine leiomyoma (UL), the most prevalent benign gynecologic tumor among reproductive-aged women, lacks sufficient research on the potential association between dietary intake and its occurrence in Korean women. Addressing this research gap, this study aims to evaluate the potential link between dietary intake and the prevalence of UL in Korean women. METHODS: In this cross-sectional study, a cohort of 672 women, aged 23 to 73, were enrolled, with 383 (57%) being premenopausal. Dietary intake was assessed using a validated food frequency questionnaire (FFQ), and UL presence was determined through ultrasonography. The analysis focused exclusively on items within ten categories, including vegetables/fruit, vegetables, fruits, red meat, processed meat, poultry, fish, dairy product, milk, and alcohol. Multiple logistic regression models were employed to explore the relationship between dietary intake and the prevalence of UL, calculating odds ratios (ORs) and 95% confidence intervals (CIs) while adjusting for confounding factors. RESULTS: Within the total cohort, 220 (32.7%) women were diagnosed with UL. High intakes of fish and poultry showed an association with higher UL prevalence. Odds ratios (95% CIs) for the upper quartiles compared to the lower quartiles were 1.68 (1.01-2.81; p trend = 0.05) for fish intake and 1.87 (1.11-3.17; p trend = 0.06) for poultry intake. Conversely, an inverse relationship emerged between dairy product intake and UL prevalence, with an odds ratio of 0.58 (95% CI 0.35-0.96; p trend = 0.05). Stratifying the analysis by menopausal status revealed a parallel pattern, with heightened UL prevalence with fish intake and reduced prevalence with dairy product intake. However, the link between poultry intake and UL prevalence was primarily observed among postmenopausal women. Among premenopausal women, elevated vegetable intake was linked to a decreased UL prevalence (OR 0.45, 95% CI 0.21-0.97 for top vs. bottom quartiles; p trend = 0.01). CONCLUSION: We found that high consumption of fish and poultry, coupled with low intake of dairy products, correlated with an elevated prevalence of UL. Furthermore, vegetable intake exhibited an inverse relationship with UL prevalence, particularly among premenopausal women.

Incidence of immunotherapy-related hyperprogressive disease (HPD) across HPD definitions and cancer types in observational studies: A systematic review and meta-analysis.

BACKGROUND: While evidence of hyperprogressive disease (HPD) continues to grow, the lack of a consensual definition obscures a proper characterization of HPD incidence. We examined how HPD incidence varies by the tumor type or the type of definition used. METHODS: We searched PubMed, Embase, the Cochrane Library of Systematic Reviews, and Web of Science from database inception to June 21, 2022. Observational studies reporting HPD incidence, in patients diagnosed with solid malignant tumors and treated with immune checkpoint inhibitors (ICI), were included. Random-effects meta-analyses were performed, and all statistical tests were 2-sided. RESULTS: HPD incidence was 12.4% (95% CI 10.2%-15.0%) with evidence of heterogeneity (Q = 119.32, p < 0.001). Meta-regression showed that the risk of developing HPD was higher in patients with advanced gastric cancer (adjusted odds ratio [OR], 10.83; 95% CI, 2.14-54.65; p < 0.001), hepatocellular carcinoma (adjusted OR, 7.99; 95% CI, 1.68-38.13; p = 0.006), non-small cell lung cancer (adjusted OR, 7.14; 95% CI, 1.58-32.29; p = 0.005), and mixed or other types (adjusted OR, 5.09; 95% CI, 1.12-23.14, p = 0.018) than in patients with renal cell carcinoma. Across definitions, HPD defined as a tumor growth kinetics ratio ≥ 2 (adjusted OR, 1.82; 95% CI, 1.08-3.07; p = 0.025) based on the Response Evaluation Criteria in Solid Tumors (RECIST) reported higher incidence than when HPD was defined as RECIST-defined progressive disease and a change in the tumor growth rate (TGR) exceeding 50% (∆TGR > 50). CONCLUSIONS: The incidence of immunotherapy-related HPD may vary across tumor types and definitions used, supporting the argument for a uniform and improved method of HPD evaluation for informed clinical decision-making.

Inhibition of Sodium-Glucose Cotransporter-2 during Serum Deprivation Increases Hepatic Gluconeogenesis via the AMPK/AKT/FOXO Signaling Pathway.

BACKGRUOUND: Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states. METHODS: Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA (siRNA), cultured in serum-free Dulbecco's modified Eagle's medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours. RESULTS: SGLT2 inhibitors dose-dependently decreased hepatic glucose uptake. Serum deprivation increased the expression levels of the gluconeogenesis genes peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), glucose 6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK), and their expression levels during serum deprivation were further increased in cells transfected with SGLT2 siRNA. SGLT2 inhibition by siRNA during serum deprivation induces nuclear localization of the transcription factor forkhead box class O 1 (FOXO1), decreases nuclear phosphorylated-AKT (p-AKT), and p-FOXO1 protein expression, and increases phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression. However, treatment with the AMPK inhibitor, compound C, reversed the reduction in the protein expression levels of nuclear p- AKT and p-FOXO1 and decreased the protein expression levels of p-AMPK and PEPCK in cells transfected with SGLT2 siRNA during serum deprivation. CONCLUSION: These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.

Potential Molecular Markers Related to Lymph Node Metastasis and Stalk Resection Margins in Pedunculated T1 Colorectal Cancers Using Digital Spatial Profiling: A Pilot Study with a Small Case Series.

There is a debate regarding the prediction of lymph node metastasis (LNM) in pedunculated T1 colorectal cancer (CRC). In this study with four cases of pedunculated T1 CRCs, we aimed to investigate gene expression variations based on the distance from the Haggitt line (HL) and identify potential molecular risk factors for LNM. By leveraging the Cancer Transcriptome Atlas and digital spatial profiling technology, we meticulously analyzed discrete regions, including the head, HL, proximal stalk region (300-1000 µm from HL), and distal stalk region (1500-2000 µm from HL) to identify spatially sequential molecular changes. Our findings showed significant overall gene expression variations among the head, proximal stalk, and distal stalk regions of pedunculated T1 CRCs compared to the control adenoma. Compared to LNM-negative T1 CRCs, LNM-positive T1 CRC showed that the expression of genes involved in immune-related pathways such as B2M, HLA-B, and HLA-E were significantly downregulated in the distal stalk region compared to the proximal stalk region. In summary, our results may tentatively suggest considering endoscopic resection of the stalk with a minimum 2000 µm margin from the HL, taking into account the gene expression alterations related to immune-related pathways. However, we acknowledge the limitations of this pilot study, notably the small case series, which may restrict the depth of interpretation. Further validation is imperative to substantiate these findings.

Lugol's Solution Reduces Positive Margins and Residual Disease After the Large Loop Excision of Transformation Zone.

OBJECTIVE: This study aimed to examine whether the intraoperative use of Lugol's solution reduces the proportion of positive resection margins (RMs) using the data of women who underwent large loop excision of the transformation zone (LLETZ). MATERIALS AND METHODS: A total of 1,751 consecutive women with cervical intraepithelial neoplasia (CIN) who underwent LLETZ with or without Lugol's solution were retrospectively retrieved from each database of 3 university hospitals in South Korea. Outcomes included positive RMs and residual disease pathologically confirmed within 6 months after LLETZ. RESULTS: Positive RMs were noted in 345 cases (19.7%). Among 1,507 women followed up, residual disease was diagnosed in 100 cases (6.6%) (69/308 cases with positive RMs; 31/1,199 cases with negative RMs). The Lugol's solution group was less likely to have positive RMs (11.8% vs 25.5%, p < .01), to require additional surgical intervention (5.4% vs 10.2%, p < .01), and to have residual disease (4.9% vs 8.0%, p = .02). On multiple logistic regression analysis, Lugol's solution reduced the proportion of positive RMs (adjusted odds ratio [aOR], 0.31). Age (50 years or older; aOR, 1.64), preconization cervical cytology (aOR, 1.53), high-risk human papillomavirus (aOR, 1.75), and CIN 2 or 3 (aOR, 2.65) were independent risk factors for margin positivity ( p < .01 for all except high-risk human papillomavirus of p = .05). CONCLUSIONS: Lugol's solution optimizes CIN treatment by reducing the proportion of positive RMs and residual disease after LLETZ.

Latent tuberculosis infection in Korean patients with multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND: Latent tuberculosis infection (LTBI) is defined as an immune response to Mycobacterium tuberculosis infection that does not manifest clinically as active tuberculosis (TB). Since some immunotherapies can alter cellular immunity, LTBI screening has been recommended for patients with multiple sclerosis (pwMS) before initiation of long-term immunotherapies. In this study, we investigated the frequency of LTBI in Korean pwMS and patients with neuromyelitis optica spectrum disorder (pwNMOSD) and reported the long-term observation of untreated LTBI under various immunotherapies. METHODS: We enrolled pwMS or pwNMOSD who visited the Neurology department of the National Cancer Center between 2017 and 2021. LTBI was determined based on positive results of interferon-gamma release assay (IGRA) using QuantiFERON Gold Plus test and no evidence of active TB. Annual chest X-ray and careful monitoring for TB symptoms were performed until April 2023 or the time of follow-up loss. RESULTS: Among 531 patients who underwent the IGRA test, 25 pwMS (10.5%) and 42 pwNMOSD (14.3%) were diagnosed with LTBI. Of the 67 patients with LTBI, 59 patients (24 pwMS and 35 pwNMOSD) declined to receive preventive anti-TB drugs. None of the 59 with untreated LTBI demonstrated TB reactivation during 74.8 person-years in pwMS and 166.1 person-years in pwNMOSD. In addition, eight patients who completed the treatment for LTBI experienced no TB reactivation for a median of 5.5 years. CONCLUSION: The LTBI prevalence in Korean pw MS and pwNMOSD was 10.5% and 14.3%, respectively, which was much higher than that in pwMS from Western countries. Notably, none of the 59 patients with untreated LTBI showed TB reactivation over 240 person-years even under long-term immunotherapies, indicating the need for additional research to stratify the risk of LTBI-reactivation.

Gout and Colorectal Cancer Likelihood: Insights from a Nested Case-Control Study of the Korean Population Utilizing the Korean National Health Insurance Service-National Sample Cohort.

Considering the global importance of both gout and colorectal cancer (CRC) as significant health issues with mutual relevance, we aimed to examine the risk of colorectal cancer in Korean patients with gout. In this nested case-control study, we used data from 9920 CRC patients and 39,680 controls the Korean National Health Insurance Service-National Sample Cohort database. Propensity score overlap-weighted multivariate logistic regression analyses, adjusted for confounders, were used to assess the odds ratio (OR) and 95% confidence interval (CI) of the association between gout and CRC. Adjusted OR for CRC were similar between patients with gout and the control group (0.95; 95% CI, 0.86-1.04; p = 0.282). However, after adjustment, subgroup analysis revealed an 18% reduction in the probability of CRC among patients younger than 65 years with gout (95% CI, 0.70-0.95; p = 0.009). Conversely, absence of an association between gout and subsequent CRC persisted regardless of sex, income, residence, and Charlson Comorbidity Index score, even among individuals aged 65 years or older. These results imply that gout may not be a significant independent risk factor for CRC among the general population. However, in patients younger than 65 years with gout, a slightly reduced likelihood of CRC was observed. Further research is necessary to establish a causal relationship between gout and CRC and to generalize these findings to other populations.

Proton Pump Inhibitors and Likelihood of Colorectal Cancer in the Korean Population: Insights from a Nested Case-Control Study Using National Health Insurance Data.

The potential connection between proton pump inhibitors (PPIs) and colorectal cancer (CRC) risk remains unclear, with specific ethnic genetic backgrounds playing a role in PPI-induced adverse effects. In this nested case-control study, we investigated the risk of CRC in relation to preceding PPI use and the duration of use using data from the Korean National Health Insurance Service-National Sample Cohort database, including 9374 incident CRC patients and 37,496 controls. To assess the impact of preceding PPI exposure (past vs. current) and use duration (days: <30, 30-90, and ≥90) on incident CRC, we conducted propensity score overlap-weighted multivariate logistic regression analyses, adjusted for confounding factors. Our findings revealed that past and current PPI users had an increased likelihood of developing CRC. Regardless of duration, individuals who used PPIs also had higher odds of developing CRC. Subgroup analyses revealed that CRC occurrence increased independent of history or duration of prior PPI use, consistent across various factors such as age, sex, income level, and residential area. These findings suggest that PPI use, regardless of past or present use and duration of use, may be related to an increased risk of developing CRC in the Korean population.

Randomized Trial on the Effect of an Oral Spleen Tyrosine Kinase Inhibitor in the Treatment of IgA Nephropathy.

Introduction: We reported increased spleen tyrosine kinase (SYK) expression in kidney biopsies of patients with IgA nephropathy (IgAN) and that inhibition of SYK reduces inflammatory cytokines production from IgA stimulated mesangial cells. Methods: This study was a double-blind, randomized, placebo-controlled phase 2 trial of fostamatinib (an oral SYK inhibitor) in 76 patients with IgAN. Patients were randomized to receive placebo, fostamatinib at 100 mg or 150 mg twice daily for 24 weeks on top of maximum tolerated dose of renin-angiotensin system inhibitors. The primary end point was reduction of proteinuria. Secondary end points included change from baseline in estimated glomerular filtration rate (eGFR) and kidney histology. Results: Although we could not detect significant reduction in proteinuria with fostamatinib overall, in a predetermined subgroup analysis, there was a trend for dose-dependent reduction in median proteinuria (from baseline to 24 weeks by 14%, 27%, and 36% in the placebo, fostamatinib 100 mg, and 150 mg groups, respectively) in patients with baseline urinary protein-to-creatinine ratios (UPCR) more than 1000 mg/g. Kidney function (eGFR) remained stable in all groups. Fostamatinib was well-tolerated. Side effects included diarrhea, hypertension, and increased liver enzymes. Thirty-nine patients underwent repeat biopsy showing reductions in SYK staining associated with therapy at low dose (-1.5 vs. 1.7 SYK+ cells/glomerulus in the placebo group, P < 0.05). Conclusions: There was a trend toward reduction in proteinuria with fostamatinib in a predefined analysis of high risk patients with IgAN despite maximal care, as defined by baseline UPCR greater than 1000 mg/g. Further study may be warranted.

Explainable machine learning using perioperative serial laboratory results to predict postoperative mortality in patients with peritonitis-induced sepsis.

Purpose: Sepsis is one of the most common causes of death after surgery. Several conventional scoring systems have been developed to predict the outcome of sepsis; however, their predictive power is insufficient. The present study applies explainable machine-learning algorithms to improve the accuracy of predicting postoperative mortality in patients with sepsis caused by peritonitis. Methods: We performed a retrospective analysis of data from demographic, clinical, and laboratory analyses, including the delta neutrophil index (DNI), WBC and neutrophil counts, and CRP level. Laboratory data were measured before surgery, 12-36 hours after surgery, and 60-84 hours after surgery. The primary study output was the probability of mortality. The areas under the receiver operating characteristic curves (AUCs) of several machine-learning algorithms using the Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score (SAPS) 3 models were compared. 'SHapley Additive exPlanations' values were used to indicate the direction of the relationship between a variable and mortality. Results: The CatBoost model yielded the highest AUC (0.933) for mortality compared to SAPS3 and SOFA (0.860 and 0.867, respectively). Increased DNI on day 3, septic shock, use of norepinephrine therapy, and increased international normalized ratio on day 3 had the greatest impact on the model's prediction of mortality. Conclusion: Machine-learning algorithms increase the accuracy of predicting postoperative mortality in patients with sepsis caused by peritonitis.

Efficacy of White Spot Syndrome Virus Protein VP28-Expressing Chlorella vulgaris as an Oral Vaccine for Shrimp.

The white spot syndrome virus (WSSV) is the causative agent of white spot disease, which kills shrimp within a few days of infection. Although WSSV has a mortality rate of almost 100% and poses a serious threat to the shrimp farming industry, strategies for its prevention and treatment are extremely limited. In this study, we examined the efficacy of VP28, a recombinant WSSV protein expressed in Chlorella vulgaris (C. vulgaris), as an oral shrimp vaccine. When compared with the control group, in which WSSV had a cumulative mortality of 100%, shrimp treated with 5% VP28-expressing C. vulgaris in their feed only had a 20% cumulative mortality rate 12 days after the WSSV challenge. When compared with the nonvaccinated group, the transcription of anti-lipopolysaccharide factor, C-type lectin, and prophenoloxidase genes, which are involved in shrimp defense against WSSV infection, was upregulated 29.6 fold, 15.4 fold, and 11.5 fold, respectively. These findings highlight C. vulgaris as a potential host for industrial shrimp vaccine production.

Usefulness of 3-Dimensional Computed Tomography Assessment of Femoral Tunnel after Anterior Cruciate Ligament Reconstruction.

Positioning of the femoral tunnel during anterior cruciate ligament (ACL) reconstruction is the most crucial factor for successful procedure. Owing to the inter-individual variability in the intra-articular anatomy, it can be challenging to obtain precise tunnel placement and ensure consistent results. Currently, the three-dimensional (3D) reconstruction of computed tomography (CT) scans is considered the best method for determining whether femoral tunnels are positioned correctly. Postoperative 3D-CT feedback can improve the accuracy of femoral tunnel placement. Precise tunnel formation obtained through feedback has a positive effect on graft maturation, graft failure, and clinical outcomes after surgery. However, even if femoral tunnel placement on 3D CT is appropriate, we should recognize that acute graft bending negatively affects surgical results. This review aimed to discuss the implementation of 3D-CT evaluation for predicting postoperative outcomes following ACL re-construction. Reviewing research that has performed 3D CT evaluations after ACL reconstruction can provide clinically significant evidence of the formation of ideal tunnels following anatomic ACL reconstruction.

Aquaporin-4-IgG positive neuromyelitis optica spectrum disorder in a paraneoplastic context.

OBJECTIVE: The association between aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and cancer via a plausible immunological response has been reported. Here, we investigated the frequency of cancer in a large cohort of patients with AQP4-IgG-NMOSD. METHODS: Between May 2005 and January 2023, patients with AQP4-IgG-NMOSD and a history of cancer were included by searching for diagnostic codes of both NMOSD and cancer in the electronic medical records and/or reviewing the database of the National Cancer Center registry of inflammatory diseases of the central nervous system. Probable paraneoplastic AQP4-IgG-NMOSD was defined according to the 2021 Criteria for Paraneoplastic Neurological Syndrome. RESULTS: Of 371 patients with AQP4-IgG-NMOSD, 23 (6.2%) had a history of cancer and four (1.1%) experienced NMOSD in a paraneoplastic context. Among the four patients with probable paraneoplastic AQP4-IgG-NMOSD, the types of cancer were lung (1 adenocarcinoma, 1 squamous cell carcinoma) and colorectal (2 adenocarcinomas). In three patients, the first NMOSD symptoms developed after a cancer diagnosis (median, 8 months [range, 4-23]), and one patient's symptoms preceded the cancer diagnosis (6 months). Compared to the 367 non-paraneoplastic patients, those in the paraneoplastic context had an older age at onset (median: 59.5 vs. 37 years, p = 0.012) and a higher proportion of longitudinally extensive transverse myelitis (LETM) as an initial manifestation (4/4[100%] vs. 130/367[35.4%], p = 0.017). CONCLUSIONS: In a large cohort of patients with AQP4-IgG-NMOSD, the frequency of cancer was low. Older age, LETM features at onset, and adenocarcinoma as the histological type were usually observed in patients with AQP4-IgG-NMOSD in a paraneoplastic context.

ß-hydroxybutyrate ameliorates sepsis-induced acute kidney injury.

BACKGROUND: Sepsis is a major cause of acute kidney injury (AKI). Recent studies have demonstrated that ß-hydroxybutyrate (ß-HB) alleviates renal ischemia-reperfusion injury and cisplatin-induced renal injury in murine models. This study aimed to investigate whether ß-HB ameliorates sepsis-induced AKI (SIAKI) in a lipopolysaccharide (LPS)-induced mouse sepsis model. METHODS AND RESULTS: SIAKI was induced by intraperitoneally injecting LPS to C57BL/6 male mice. ß-HB was administrated intraperitoneally before LPS injection. The mice were divided into sham, ß-HB, LPS, and ß-HB + LPS groups. The histological damage score and serum creatinine level were significantly increased in the LPS group mice, but attenuated in the ß-HB + LPS group mice. The expression of phosphorylated nuclear factor-κB tumor necrosis factor-α/interleukin-6 and the number of F4/80-positive macrophages in the ß-HB + LPS group mice were lower than those in the LPS group mice. The number of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells, cleaved caspase-3 expression, and Bax/Bcl-2 ratio in the ß-HB + LPS group mice were lower than those in the LPS group mice. CONCLUSION: ß-HB pre-treatment ameliorates SIAKI by reducing tubular apoptosis and inflammatory responses. Thus, ß-HB pre-treatment could be a potential prophylactic strategy against SIAKI.

Oncologic relevance of genetic alterations in sporadic synchronous and solitary colorectal cancer: a retrospective multicenter study.

BACKGROUND: Oncologic impact of genetic alteration across synchronous colorectal cancer (CRC) still remains unclear. This study aimed to compare the oncologic relevance according to genetic alteration between synchronous and solitary CRC with performing systematic review. METHODS: Multicenter retrospective analysis was performed for CRC patients with curative resection. Genetic profiling was consisted of microsatellite instability (MSI) testing, RAS (K-ras, and N-ras), and BRAF (v-Raf murine sarcoma viral oncogene homolog B1) V600E mutation. Multivariate analyses were conducted using logistic regression for synchronicity, and Cox proportional hazard model with stage-adjusting for overall survival (OS) and disease-free survival (DFS). RESULTS: It was identified synchronous (n = 36) and solitary (n = 579) CRC with similar base line characteristics. RAS mutation was associated to synchronous CRC with no relations of MSI and BRAF. During median follow up of 77.8 month, Kaplan-meier curves showed significant differences according to MSI-high for OS, and in RAS, and BRAF mutation for DFS, respectively. In multivariable analyses, RAS and BRAF mutation were independent factors (RAS, HR = 1.808, 95% CI = 1.18-2.77, p = 0.007; BRAF, HR = 2.417, 95% CI = 1.32-4.41, p = 0.004). Old age was independent factor for OS (HR = 3.626, 95% CI = 1.09-12.00, p = 0.035). CONCLUSION: This study showed that oncologic outcomes might differ according to mutation burden characterized by RAS, BRAF, and MSI between synchronous CRC and solitary CRC. In addition, our systematic review highlighted a lack of data and much heterogeneity in genetic characteristics and survival outcomes of synchronous CRC relative to that of solitary CRC.