Lanthanum-calcium bimetallic-modified attapulgite- chitosan hydrogel beads for efficient phosphate removal from water: Performance evaluation, mechanistic and life cycle assessment.

Phosphorus is a critical factor in the control of eutrophication. We developed a three-dimensional porous, bimetallic-modified adsorbent La-Ca-CS/ATP to remove excess phosphate from water. Langmuir model showed that the theoretical adsorption capacity of La-Ca-CS/ATP was up to 123 mg P/g. The amount of La and Ca leached by La-Ca-CS/ATP was small, and the adsorption of 36.08 mg P/g was maintained during the five cycles of La-Ca-CS/ATP. The La-Ca-CS/ATP adsorption mechanism mainly involved surface precipitation, ligand exchange, electrostatic attraction, and inner-sphere complexation. Molecular dynamics demonstrated that La and Ca had complementary effects on binding sites and energy barriers within the range of 0.5-0.7 nm and 1.2-2 nm, enhancing the adsorption effect of La-Ca-CS/ATP. The life cycle assessment results showed that adding calcium could help reduce the environmental impact of lanthanum and chitosan. The production of La-Ca-CS/ATP adsorbed 73.88 P mg/g and emitted 24.73 kg CO2 eq, which was less than other adsorbents.

Prognostic significance of postoperative complications for patients with hepatocellular carcinoma relative to alpha-feto protein and tumor burden score.

BACKGROUND: We sought to elucidate the impact of postoperative complications on patient outcomes relative to differences in alpha-fetoprotein-tumor burden score (ATS) among patients with hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection of HCC between 2000 and 2020 were identified from an international database. Moderate/severe complications were defined using the optimal cut-off value of the comprehensive complication index (CCI) based on the log-rank test. RESULTS: A total of 1124 patients was included. CCI cut-off value of 16.6 was identified as the optimal prognostic threshold. Patients who experienced moderate/severe complications were more likely to have worse recurrence free survival [RFS] versus individuals who had no/mild complications (2-year RFS; no/mild complication: 55.9% vs. moderate/severe complication: 38.1% p < 0.001). Of note, low and medium ATS patients who experienced moderate/severe complications had a higher risk of recurrence (2-year RFS; no/mild complication: postoperative complications 70.0% vs. moderate/severe complication: 51.1%, p = 0.006; medium: no/mild complication: 50.8% vs moderate/severe complication: 56.7%, p = 0.01); however, postoperative complications were not associated with worse outcomes among patients with high ATS (no/mild complication: 39.1% vs. moderate/severe complication: 29.2%, p = 0.20). CONCLUSION: These data serve to emphasize how reduction in postoperative complications may be crucial to improve prognosis, particularly among patients with favorable HCC characteristics.

Development and validation of nomograms to predict survival and recurrence after hepatectomy for intermediate/advanced (BCLC stage B/C) hepatocellular carcinoma.

BACKGROUND: Despite the Barcelona Clinic Liver Cancer system discouraging hepatectomy for intermediate/advanced hepatocellular carcinoma, the procedure is still performed worldwide, particularly in Asia. This study aimed to develop and validate nomograms for predicting survival and recurrence for these patients. METHODS: We analyzed patients who underwent curative-intent hepatectomy for intermediate/advanced hepatocellular carcinoma between 2010 and 2020 across 3 Chinese hospitals. The Eastern Hepatobiliary Surgery Hospital cohort was used as the training cohort for the nomogram construction, and the Jilin First Hospital and Fujian Mengchao Hepatobiliary Hospital cohorts served as the external validation cohorts. Independent preoperative predictors for survival and recurrence were identified through univariable and multivariable Cox regression analyses. Predictive accuracy was measured using the concordance index and calibration curves. The predictive performance between nomograms and conventional hepatocellular carcinoma staging systems was compared. RESULTS: A total of 1,328 patients met the inclusion criteria. The nomograms for predicting survival and recurrence were developed using 10 and 6 independent variables, respectively. Nomograms' concordance indices in the training cohort were 0.777 (95% confidence interval 0.759-0.800) and 0.719 (95% confidence interval 0.697-0.742) for survival and recurrence, outperforming 4 conventional staging systems (P < .001). Nomograms accurately stratified risk into low, intermediate, and high subgroups. These results were validated well by 2 external validation cohorts. CONCLUSION: We developed and validated nomograms predicting survival and recurrence for patients with intermediate/advanced hepatocellular carcinoma, contradicting Barcelona Clinic Liver Cancer surgical guidelines. These nomograms may facilitate clinicians to formulate personalized surgical decisions, estimate long-term prognosis, and strategize neoadjuvant/adjuvant anti-recurrence therapy.

Sex disparity in clinical characteristics and long-term prognosis after liver resection for patients with intrahepatic cholangiocarcinoma: A propensity score matching analysis.

Aim: To compare the survival outcomes between male and female patients with intrahepatic cholangiocarcinoma who underwent liver resection. Methods: Data from 976 consecutive intrahepatic cholangiocarcinoma patients undergoing liver resection between January 2005 and May 2013 at the Eastern Hepatobiliary Surgery Hospital were prospectively collected and retrospectively reviewed. Patient clinicopathological characteristics, overall survival, and cumulative recurrence rates were compared between male and female patients using propensity score matching. Results: Propensity score matching generated 313 matched pairs of patients. Among the entire cohort, the 1-, 3-, and 5-year overall survival and recurrence rates of the male and female patients were 60.2 %, 37.3 %, and 27.7 % vs. 65.8 %, 40.4 %, and 31.0 % (P = 0.380) and 50.6 %, 67.4 %, and 74.2 % vs. 44.4 %, 63.5 %, and 69.6 % (P = 0.123), respectively. In the matched cohort, the 1-, 3-, and 5-year overall survival and recurrence rates of the male and female patients were 60.6 %, 35.9 % and 22.4 % vs. 66.4 %, 40.6 % and 31.1 % (P = 0.041) and 51.5 %, 69.3 % and 83.9 % vs. 44.3 %, 63.6 %, and 69.9 % (P = 0.041), respectively. After adjustment for other confounding variables by multivariate Cox regression analysis, male sex was independently associated with worse overall survival (hazard ratio = 1.322, 95 % confidence interval: 1.079-1.621, P = 0.007) and tumor recurrence (hazard ratio = 1.337, 95 % confidence interval: 1.088-1.645, P = 0.006). A subgroup analysis of patients younger than 55 years old after propensity score matching showed that male patients had significantly worse overall survival and higher recurrence rates than female patients after surgery, while no significant difference in long-term overall survival and recurrence was observed between male and female patients older than 55 years old after propensity score matching. Conclusion: Male sex was an independent risk factor for overall survival and tumor recurrence in patients after liver resection for intrahepatic cholangiocarcinoma.

The Glucose Transporter 5 Enhances CAR-T Cell Metabolic Function and Anti-tumour Durability.

Activated T cells undergo a metabolic shift to aerobic glycolysis to support the energetic demands of proliferation, differentiation, and cytolytic function. Transmembrane glucose flux is facilitated by glucose transporters (GLUT) that play a vital role in T cell metabolic reprogramming and anti-tumour function. GLUT isoforms are regulated at the level of expression and subcellular distribution. GLUTs also display preferential selectivity for carbohydrate macronutrients including glucose, galactose, and fructose. GLUT5, which selectively transports fructose over glucose, has never been explored as a genetic engineering strategy to enhance CAR-T cells in fructose-rich tumour environments. Fructose levels are significantly elevated in the bone marrow and the plasma of acute myeloid leukaemia (AML) patients. Here, we demonstrate that the expression of wild-type GLUT5 restores T cell metabolic fitness in glucose-free, high fructose conditions. We find that fructose supports maximal glycolytic capacity and ATP replenishment rates in GLUT5-expressing T cells. Using steady state tracer technology, we show that 13C6 fructose supports glycolytic reprogramming and TCA anaplerosis in CAR-T cells undergoing log phase expansion. In cytotoxicity assays, GLUT5 rescues T cell cytolytic function in glucose-free medium. The fructose/GLUT5 metabolic axis also supports maximal migratory velocity, which provides mechanistic insight into why GLUT5-expressing CAR-Ts have superior effector function as they undergo "hit-and-run" serial killing. These findings translate to superior anti-tumour function in a xenograft model of AML. In fact, we found that GLUT5 enhances CAR-T cell anti-tumour function in vivo without any need for fructose intervention. Accordingly, we hypothesize that GLUT5 is sufficient to enhance CAR-T resilience by increasing the cells' competitiveness for glucose at physiologic metabolite levels. Our findings have immediate translational relevance by providing the first evidence that GLUT5 confers a competitive edge in a fructose-enriched milieu, and is a novel approach to overcome glucose depletion in hostile tumour microenvironments (TMEs).

Prognostic value of peripheral blood neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, pan-immune-inflammation value and systemic immune-inflammation index for the efficacy of immunotherapy in patients with advanced gastric cancer.

Aim: The study aimed to assess the value of pretreatment peripheral blood neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), pan-immune-inflammation value (PIV) and systemic immune-inflammation index (SII) for predicting immunotherapy prognosis and efficacy in advanced gastric cancer (GC). Methods: A total of 84 advanced GC patients received immunotherapy were retrospectively collected. The optimal cut-off values were determined by receiver operating characteristic curves. The univariate and multivariate analysis investigated the effects of NLR, PLR, PIV and SII on patients prognosis. Results: NLR, PLR, PIV and SII had predictive value of efficacy. NLR ≥3.65 was an independent risk factor for worse outcomes. Conclusion: NLR, PLR, PIV and SII have predictive value of efficacy and NLR ≥3.65 suggests a poor prognosis following immunotherapy in advanced GC.

Immunotherapy can make gastric cancer patients live longer. However, not all patients live longer. We need simple, inexpensive and effective indicators to find patients who can live longer with immunotherapy. Routine blood test is common in our daily lives. Previous studies reported that some indicators in routine blood test can predict the prognosis and efficacy of surgery in gastric cancer patients. But it is not clear in immunotherapy for advanced gastric cancer patients. In our trial, we found that some indicators in routine blood test can help predict the effect of immunotherapy in patients with advanced gastric cancer and screen which patients will live longer with immunotherapy.

Textbook outcome in liver surgery: open vs minimally invasive hepatectomy among patients with hepatocellular carcinoma.

BACKGROUND: We sought to investigate whether minimally invasive hepatectomy (MIH) was superior to open hepatectomy (OH) in terms of achieving textbook outcome in liver surgery (TOLS) after resection of hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection of HCC between 2000 and 2020 were identified from an international database. TOLS was defined by the absence of intraoperative grade ≥2 events, R1 resection margin, posthepatectomy liver failure, bile leakage, major complications, in-hospital mortality, and readmission. RESULTS: A total of 1039 patients who underwent HCC resection were included in the analysis. Although most patients underwent OH (n = 724 [69.7%]), 30.3% (n = 315) underwent MIH. Patients who underwent MIH had a lower tumor burden score (3.6 [IQR, 2.6-5.2] for MIH vs 6.1 [IQR, 3.9-10.1] for OH) and were more likely to undergo minor hepatectomy (84.1% [MIH] vs 53.6% [OH]) than patients who had an OH (both P < .001). After propensity score matching to control for baseline differences between the 2 cohorts, the incidence of TOLS was comparable among patients who had undergone MIH (56.6%) versus OH (64.8%) (P = .06). However, MIH was associated with a shorter length of hospital stay (6.0 days [IQR, 4.0-8.0] for MIH vs 9.0 days [IQR, 6.0-12.0] for OH). Among patients who had MIH, the odds ratio of achieving TOLS remained stable up to a tumor burden score of 4; after which the chance of TOLS with MIH markedly decreased. CONCLUSION: Patients with HCC who underwent resection with MIH versus OH had a comparable likelihood of TOLS, although MIH was associated with a short length of stay.

Vortex sorting of rare particles/cells in microcavities: A review.

Microfluidics or lab-on-a-chip technology has shown great potential for the separation of target particles/cells from heterogeneous solutions. Among current separation methods, vortex sorting of particles/cells in microcavities is a highly effective method for trapping and isolating rare target cells, such as circulating tumor cells, from flowing samples. By utilizing fluid forces and inertial particle effects, this passive method offers advantages such as label-free operation, high throughput, and high concentration. This paper reviews the fundamental research on the mechanisms of focusing, trapping, and holding of particles in this method, designs of novel microcavities, as well as its applications. We also summarize the challenges and prospects of this technique with the hope to promote its applications in medical and biological research.

Experimental investigation of confinement effect in single molecule amplification via real-time digital PCR on a multivolume droplet array SlipChip.

BACKGROUND: Digital polymerase chain reaction (digital PCR) is an important quantitative nucleic acid analysis method in both life science research and clinical diagnostics. One important hypothesis is that by physically constraining a single nucleic acid molecule in a small volume, the relative concentration can be increased therefore further improving the analysis performance, and this is commonly defined as the confinement effect in digital PCR. However, experimental investigation of this confinement effect can be challenging since it requires a microfluidic device that can generate partitions of different volumes and an instrument that can monitor the kinetics of amplification. (96). RESULTS: Here, we developed a real-time digital PCR system with a multivolume droplet array SlipChip (Muda-SlipChip) that can generate droplet of 125 nL, 25 nL, 5 nL, and 1 nL by a simple "load-slip" operation. In the digital region, by reducing the volume, the relative concentration is increased, the amplification kinetic can be accelerated, and the time to reach the fluorescence threshold, or Cq value, can be reduced. When the copy number per well is much higher than one, the relative concentration is independent of the partition volume, thus the amplification kinetics are similar in different volume partitions. This system is not limited to studying the kinetics of digital nucleic acid amplification, it can also extend the dynamic range of the digital nucleic acid analysis by additional three orders of magnitude by combining a digital and an analog quantification algorithm. (140). SIGNIFICANCE: In this study, we experimentally investigated for the first time the confinement effect in the community of digital PCR via a new real-time digital PCR system with a multivolume droplet array SlipChip (Muda-SlipChip). And a wider dynamic range of quantification methods compared to conventional digital PCR was validated by this system. This system provides emerging opportunities for life science research and clinical diagnostics. (63).

YBX1 promotes stemness and cisplatin insensitivity in intrahepatic cholangiocarcinoma via the AKT/ß-catenin axis.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy characterized by a poor prognosis and closely linked to tumor stemness. However, the key molecules that regulate ICC stemness remain elusive. Although Y-box binding protein 1 (YBX1) negatively affects prognosis in various cancers by enhancing stemness and chemoresistance, its effect on stemness and cisplatin sensitivity in ICC remains unclear. METHODS: Three bulk and single-cell RNA-seq datasets were analyzed to investigate YBX1 expression in ICC and its association with stemness. Clinical samples and colony/sphere formation assays validated the role of YBX1 in stemness and sensitivity to cisplatin. AZD5363 and KYA1979K explored the interaction of YBX1 with the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) and WNT/ß-catenin pathways. RESULTS: YBX1 was significantly upregulated in ICC, correlated with worse overall survival and shorter postoperative recurrence time, and was higher in chemotherapy-non-responsive ICC tissues. The YBX1-high group exhibited significantly elevated stemness scores, and genes linked to YBX1 upregulation were enriched in multiple stemness-related pathways. Moreover, YBX1 expression is significantly correlated with several stemness-related genes (SOX9, OCT4, CD133, CD44 and EPCAM). Additionally, YBX1 overexpression significantly enhanced the colony- and spheroid-forming abilities of ICC cells, accelerated tumor growth in vivo and reduced their sensitivity to cisplatin. Conversely, the downregulation of YBX1 exerted the opposite effect. The transcriptomic analysis highlighted the link between YBX1 and the PI3K/AKT and WNT/ß-catenin pathways. Further, AZD5363 and KYA1979K were used to clarify that YBX1 promoted ICC stemness through the regulation of the AKT/ß-catenin axis. CONCLUSIONS: YBX1 is upregulated in ICC and promotes stemness and cisplatin insensitivity via the AKT/ß-catenin axis. Our study describes a novel potential therapeutic target for improving ICC prognosis.

Optimizing lipid control in Taiwanese diabetic patients: A collaborative consensus by the Diabetes Association of the Republic of China (Taiwan) and the Taiwanese Association of Diabetes Educators.

We present an in-depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low-density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence-based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.

Efficient isomerization of glucose into fructose by MgO-doped lignin-derived ordered mesoporous carbon.

The conversion of glucose into fructose can transform cellulose into high-value chemicals. This study introduces an innovative synthesis method for creating an MgO-based ordered mesoporous carbon (MgO@OMC) catalyst, aimed at the efficient isomerization of glucose into fructose. Throughout the synthesis process, lignin serves as the exclusive carbon precursor, while Mg2+ functions as both a crosslinking agent and a metallic active center. This enables a one-step synthesis of MgO@OMC via a solvent-induced evaporation self-assembly (EISA) method. The synthesized MgO@OMCs exhibit an impeccable 2D hexagonal ordered mesoporous structure, in addition to a substantial specific surface area (378.2 m2/g) and small MgO nanoparticles (1.52 nm). Furthermore, this catalyst was shown active, selective, and reusable in the isomerization of glucose to fructose. It yields 41 % fructose with a selectivity of up to 89.3 % at a significant glucose loading of 7 wt% in aqueous solution over MgO0.5@OMC-600. This performance closely rivals the current maximum glucose isomerization yield achieved with solid base catalysts. Additionally, the catalyst retains a fructose selectivity above 60 % even after 4 cycles, a feature attributable to its extended ordered mesoporous structure and the spatial confinement effect of the OMCs, bestowing it with high catalytic efficiency.

The complication-overall survival (CompOS) risk tool predicts risk of a severe postoperative complications relative to long-term survival among patients with primary liver cancer.

BACKGROUND: This study aimed to develop a tool based on preoperative factors to predict the risk of perioperative complications based on the Comprehensive Complication Index (CCI) and long-term survival outcomes after liver resection for primary liver cancer. METHODS: Patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) undergoing curative-intent hepatectomy between 1990 and 2020 were identified using a multi-institutional international database. RESULTS: Among 1411 patients who underwent curative-intent hepatic resection (HCC: 997, 70.7%; ICC: 414, 29.3%), median patient age was 66.0 years (IQR, 57.0-73.0), and most patients were male (n = 1001, 70.9%). In the postoperative setting, 699 patients (49.5%) experienced a complication; moreover, 112 patients (7.9%) had major complications. Although most patients had a favorable risk complication-overall survival (CompOS) profile (CCI score > 40 risk of <30% and median survival of >5 years: n = 778, 55.1%), 553 patients (39.2%) had an intermediate-risk profile, and 80 patients (5.7%) had a very unfavorable risk profile (CCI score > 40 risk of ≥30% and/or median survival of ≤1.5 years). The areas under the curve of the test and validation cohorts were 0.73 and 0.76, respectively. CONCLUSION: The CompOS risk model accurately stratified patients relative to short- and long-term risks, identifying a subset of patients at a high risk of major complications and poor overall survival.

An Improved A-Star Path Planning Algorithm Based on Mobile Robots in Medical Testing Laboratories.

In the blood sample management pipeline environment, we have innovatively improved the traditional A-star algorithm to enhance the efficiency of mobile robots. This study employs a grid environmental modeling approach to accurately simulate medical testing laboratories. On the grid map, we utilize an 8-neighbor search method for path planning to accommodate the complex structure within the laboratory. By introducing an improved evaluation function and a bidirectional search strategy, we have successfully reduced the number of search nodes and significantly improved path search efficiency. Additionally, we eliminate redundant nodes in the path, smooth the path using cubic uniform B-spline curves, remove unnecessary inflection points, and further optimize the motion trajectory of the robot. The experimental results of the path planning simulation under different scenarios and specifications show that the improved A-star algorithm has higher search efficiency and traverses fewer nodes compared to the traditional A-star algorithm and the bidirectional A-star algorithm. Overall, the simulation experiments verify the feasibility of the improved A-star algorithm, which can better meet the needs of actual mobile robots in real medical testing laboratories.

Enhancing Soybean and Maize Yields through Improved Nitrogen and Soil Water Use Efficiencies: A 40-Year Study on the Impact of Farmyard Manure Amendment in Northeast China.

The combined application of manure and chemical fertilizers has been recognized as a critical factor driving significant changes in crop yield and nutrient use efficiency, holding the potential to optimize agricultural management to achieve high yields. In this 40-year study, we investigated the effect of manure amendment on soybean and maize yields, water and nitrogen use efficiencies (WUE and NUE), and water and mineral N storage at 0-100 cm soil depths from 2017 to 2018 to explore the optimization of fertilization management strategies for soybean and maize production in Northeast China. To elucidate the impact of chemical fertilizers and manure, twelve treatments-control (CK); single N fertilizer at a low rate (N1) and that at a high rate (N2); N1, phosphorus (P), and potassium (K) fertilizer (N1PK); manure alone at 13.5 and 27 t ha-1 (M1 and M2); and those combined with N, P, or K fertilizer (M1N1, M1N2, and M1N1PK and M2N1, M2N2, and M2N1PK)-were selected and studied. The results showed that long-term amendment with manure significantly increased crop biomass and yield in the soybean-maize-maize rotation system. Combining with manure increased the WUE, the partial factor productivity of N fertilizer (PFPN), and N physiological efficiency (PEN) in both the soybean and maize seasons; conserved soil water (mainly at 40-60 cm); and increased soil N retention (in the upper 60 cm layer), which reduced the risk of N leaching, with a better effect being observed after the application of 13.5 t ha-1 manure. These results provide insight into the potential of using fertilization management strategies that include amendment with 13.5 t ha-1 manure in combination with N, P, and K fertilizer in the maize season and only chemical fertilizer in the soybean season, as these results indicate that such strategies can achieve high yields and be used to implement agricultural sustainable development in brown soil regions in Northeast China.

Recurrent Intrahepatic Cholangiocarcinoma: A 10-Point Score to Predict Post-Recurrence Survival and Guide Treatment of Recurrence.

INTRODUCTION: Although up to 50-70% of patients with intrahepatic cholangiocarcinoma (ICC) recur following resection, data to predict post-recurrence survival (PRS) and guide treatment of recurrence are limited. METHODS: Patients who underwent resection of ICC between 2000 and 2020 were identified from an international, multi-institutional database. Data on primary disease as well as laboratory and radiologic data on recurrent disease were collected. Factors associated with PRS were examined and a novel scoring system to predict PRS (PRS score) was developed and internally validated. RESULTS: Among 986 individuals who underwent resection for ICC, 588 (59.6%) patients developed recurrence at a median follow up of 20.3 months. Among patients who experienced a recurrence, 97 (16.5%) underwent re-resection/ablation for recurrent ICC; 88 (15.0%) and 403 (68.5%) patients received intra-arterial treatment or systemic chemotherapy/supportive therapy, respectively. Patient American Society of Anesthesiologists (ASA) class > 2 (1 point), primary tumor N1/Nx status (1 point), primary R1 resection margin (1 point), primary tumor G3/G4 grade (1 point), carbohydrate antigen (CA) 19-9 > 37 UI/mL (2 points) at recurrence and carcinoembryonic antigen (CEA) > 5 ng/mL (2 points) at recurrence, as well as recurrent bilateral disease (1 point) and early recurrence (1 point) were included in the PRS score. The PRS score successfully stratified patients relative to PRS and demonstrated strong discriminatory ability (C-index 0.70, 95% confidence interval 0.68-0.72). While a PRS score of 0-3 was associated with a 3-year PRS of 62.5% following resection/ablation for recurrent ICC, a PRS score > 3 was associated with a low 3-year PRS of 35.5% (p = 0.03). CONCLUSIONS: The PRS score demonstrated strong discriminatory ability to predict PRS among patients who had developed recurrence following initial resection of ICC. The PRS score may be a useful tool to guide treatment among patients with recurrent ICC.

Predicting risk of recurrence after resection of stage I intrahepatic cholangiocarcinoma.

BACKGROUND: Early-stage intrahepatic cholangiocarcinoma (ICC) is often an indication of curative-intent resection. Although patients with early-stage ICC generally have a better prognosis than individuals with advanced ICC, the incidence and risk factors of recurrence after early-stage ICC remain unclear. METHODS: A multi-institutional database was used to identify patients who underwent surgery between 2000 and 2018 for ICC with pathologically confirmed stage I disease. Cox regression analysis was used to identify clinicopathological factors associated with recurrence, and an online prediction model was developed and validated. RESULTS: Of 430 patients diagnosed with stage I ICC, approximately one-half of patients (n = 221, 51.4%) experienced recurrence after curative-intent resection. Among patients with a recurrence, most (n = 188, 85.1%) experienced it within 12 months. On multivariable analysis, carcinoembryonic antigen (hazard ratio [HR], 1.011; 95% CI, 1.004-1.018), systemic immune-inflammation index (HR, 1.036; 95% CI, 1.019-1.056), no lymph nodes evaluated (HR, 1.851; 95% CI, 1.276-2.683), and tumor size (HR, 1.101; 95% CI, 1.053-1.151) were associated with greater hazards of recurrence. A predictive model that included these weighted risk factors demonstrated excellent prognostic discrimination in the test (12-month recurrence-free survival [RFS]: low risk, 80.1%; intermediate risk, 60.3%; high risk, 37.7%; P = .001) and validation (12-month RFS: low risk, 84.5%; intermediate risk, 63.5%; high risk, 47.1%; P = .036) datasets. The online predictive model was made available at https://ktsahara.shinyapps.io/stageI_icc/. CONCLUSIONS: Patients with stage I ICC without vascular invasion or lymph node metastasis had a relatively high incidence of recurrence. An online tool can risk stratify patients relative to recurrence risk to identify individuals best suited for alternative treatment approaches.

Study on the predictive value of pretreatment peripheral blood inflammatory markers regarding immunotherapy in patients with inoperable advanced or locally advanced oesophageal squamous cell carcinoma.

OBJECTIVE: To explore the effects of pretreatment peripheral blood panimmune-inflammation value (PIV), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) on the efficacy and prognostic value of immunotherapy in patients with inoperable advanced or locally advanced oesophageal squamous cell carcinoma (ESCC). METHODS: Clinical data of 107 inoperable advanced or locally advanced ESCC patients were retrospectively analysed between May 2019 and August 2023, the receiver operating characteristic curves (ROCs) of PIV, SII, NLR, and PLR in patients prior to immunotherapy were plotted, and their optimal cutoff values were determined. The risk factors were determined by univariate and multivariate analyses in groups based on the optimal cut-off values. RESULTS: Peripheral blood PIV, SII and PLR before immunotherapy had predictive value for the optimal efficacy of immunotherapy in patients with inoperable advanced or locally advanced ESCC; patients with PIV ≥415.885, SII ≥834.295 and NLR ≥3.740 had a low objective response rate (ORR), disease control rate (DCR), a short progression-free survival (PFS) and overall survival (OS) after immunotherapy (p < 0.05). Patient tumour stage, distant lymph node metastasis, lung metastasis, liver metastasis, PIV, SII, and NLR were risk factors affecting PFS and OS (p < 0.05). Tumour stage and SII were independent risk factors affecting PFS and OS (p < 0.05). CONCLUSION: In patients with inoperable advanced or locally advanced ESCC, peripheral blood PIV, SII, and NLR have predictive value for immunotherapy outcome, SII is an independent risk factor affecting the survival prognosis, and SII ≥834.295 suggests a poor prognosis from immunotherapy.

Effects of beta-blockers use on mortality of patients with acute respiratory distress syndrome: a retrospective cohort study.

Introduction: Acute respiratory distress syndrome (ARDS) remains a challenging disease with limited prevention and treatment options. The usage of beta-blockers may have potential benefits in different critical illnesses. This study aimed to investigate the correlation between beta-blocker therapy and mortality in patients with ARDS. Materials and methods: This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care (MIMIC) IV database and focused on patients diagnosed with ARDS. The primary outcome of the study was 30-day mortality. To account for confounding factors, a multivariable analysis was performed. Propensity score matching (PSM) was carried out on a 1:1 ratio. Robust assessments were conducted using inverse probability weighting (IPTW), standardized mortality ratio weighting (SMRW), pairwise algorithms (PA), and overlap weights (OW). Results: A total of 1,104 patients with ARDS were included in the study. Univariate and multivariate Cox regression analyses found that the 30-day mortality for 489 patients (23.7%) who received beta-blockers was significantly lower than the mortality rate of 615 patients (35.9%) who did not receive beta-blockers. After adjusting for potential confounders through PSM and propensity score, as well as utilizing IPTW, SMRW, PA, and OW, the results remained robust, with the hazard ratios (HR) ranging from 0.42 to 0.58 and all p-values < 0.001. Evaluation of the E-values indicated the robustness of the results even in the presence of unmeasured confounding. Conclusion: The findings suggest a potential association between beta-blocker usage and reduced mortality in critically ill patients with ARDS. However, further validation of this observation is needed through randomized controlled trials.