The Barthel Index predicts surgical textbook outcomes following hepatectomy for elderly patients with hepatocellular carcinoma: A multicenter cohort study.

BACKGROUND: The burgeoning demand for hepatectomy in elderly patients with hepatocellular carcinoma (HCC) necessitates improved perioperative care. Geriatric populations frequently experience functional decline and frailty, predisposing them to adverse postoperative outcomes. The Barthel Index serves as a reliable measure for assessing functional capacity, and this study evaluates its impact on surgical textbook outcomes (TOs) in elderly HCC patients. METHODS: A multicenter retrospective cohort study analyzed elderly patients (≥70 years) following hepatectomy for HCC between 2013 and 2021. Utilizing a Barthel Index cut-off value of 85, patients were divided into two groups: with and without preoperative functional decline and frailty. The primary outcome was the rate of TO, encompassing seven criteria. TO rates were compared between groups, and multivariate logistic regression analyses identified independent risks for achieving TOs. RESULTS: Of 497 elderly patients, 157 (31.6 â€‹%) exhibited preoperative functional decline and frailty (Barthel Index score <85). The overall TO rate was 58.6 â€‹%. Patients with preoperative Barthel Index score <85 had significantly lower TO rates compared to patients with score ≥85 (29.3 â€‹% vs. 72.1 â€‹%, P â€‹< â€‹0.001). Multivariate analysis revealed preoperative Barthel Index score <85 as an independent risk for achieving TO (odds ratio 3.413, 95 â€‹% confidence interval 1.879-6.198, P â€‹< â€‹0.001). Comparable results were observed in the subgroups of patients undergoing open and laparoscopic hepatectomy. CONCLUSION: Preoperative Barthel Index-based assessment of functional decline and frailty significantly predicts TOs following hepatectomy in elderly HCC patients, enabling identification of high-risk patients and informing preoperative management and postoperative care within geriatric oncology.

Dissecting microenvironment in cystadenomas and hepatic cysts based on single nucleus RNA-sequencing data.

Hepatic cystadenoma is a rare disease, accounting for about 5% of all cystic lesions, with a high tendency of malignant transformation. The preoperative diagnosis of cystadenoma is difficult, and some cystadenomas are easily misdiagnosed as hepatic cysts at first. Hepatic cyst is a relatively common liver disease, most of which are benign, but large hepatic cysts can lead to pressure on the bile duct, resulting in abnormal liver function. To better understand the difference between the microenvironment of cystadenomas and hepatic cysts, we performed single-nuclei RNA-sequencing on cystadenoma and hepatic cysts samples. In addition, we performed spatial transcriptome sequencing of hepatic cysts. Based on nucleus RNA-sequencing data, a total of seven major cell types were identified. Here we described the tumor microenvironment of cystadenomas and hepatic cysts, particularly the transcriptome signatures and regulators of immune cells and stromal cells. By inferring copy number variation, it was found that the malignant degree of hepatic stellate cells in cystadenoma was higher. Pseudotime trajectory analysis demonstrated dynamic transformation of hepatocytes in hepatic cysts and cystadenomas. Cystadenomas had higher immune infiltration than hepatic cysts, and T cells had a more complex regulatory mechanism in cystadenomas than hepatic cysts. Immunohistochemistry confirms a cystadenoma-specific T-cell immunoregulatory mechanism. These results provided a single-cell atlas of cystadenomas and hepatic cyst, revealed a more complex microenvironment in cystadenomas than in hepatic cysts, and provided new perspective for the molecular mechanisms of cystadenomas and hepatic cyst.

A Case Report of Mycoplasma pneumoniae-induced fulminant myocarditis in a 15-year-old male leading to cardiogenic shock and electrical storm.

Mycoplasma pneumoniae (M. pneumoniae) is a well-recognized pathogen primarily associated with respiratory tract infections. However, in rare instances, it can lead to extrapulmonary manifestations, including myocarditis. We present a case of a 15-year-old male who developed fulminant myocarditis, cardiogenic shock, and cardiac electrical storm attributed to M. pneumoniae infection. He underwent a combination of intra-aortic balloon pump (IABP) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiac support, ultimately surviving despite the intracardiac thrombus formation and embolic stroke. Following comprehensive treatment and rehabilitation, he was discharged in stable condition. This case underscores the importance of considering atypical pathogens as potential etiological factors in patients presenting with cardiac complications, especially in the adolescents. It also emphasizes the need for clinical vigilance and effective support for potential cardiac complications arising from M. pneumoniae infection.

Efficacy and safety of heparin for sepsis-induced disseminated intravascular coagulation (HepSIC): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Disseminated intravascular coagulation (DIC) occurs in 30-50% of septic patients and contributes to high mortality in the intensive care unit (ICU). However, there are few proven interventions for coagulation disorder management in sepsis. Experimental and clinical data have demonstrated that sepsis could benefit from unfractionated heparin (UFH) treatment. To date, there are no large multicenter trials to determine the safety and efficacy of UFH in septic patients with suspected DIC. METHODS: A multicenter, double-blinded, placebo-controlled randomized trial is designed to recruit 600 patients who met sepsis 3.0 criteria and suspected DIC. Participants will be randomized (1:1) to receive UFH or saline via continuous intravenous administration for 7 days within 6 h of enrolment. The primary outcome is ICU mortality. The secondary outcome includes 28-day all-cause mortality, the improvement of Sequential Organ Failure Assessment scores, and the incidence of major hemorrhage. Investigators, participants, and statisticians will be blinded to the allocation. DISCUSSION: The HepSIC trial is to evaluate the efficacy and safety of UFH on sepsis-related DIC across different areas of China. The small dosage of UFH administration would offer a new potential approach for treating sepsis-related coagulation disorders. ETHICS AND DISSEMINATION: Ethical approval was granted by all the ethics committees of 20 participant centers. Results will be disseminated via peer-reviewed publications and presented at conferences. TRIAL REGISTRATION: ClinicalTrials.gov NCT02654561. Registered on 13 January 2016.

Development and validation of prealbumin-bilirubin score (preALBI score) for predicting long-term survival after hepatectomy for hepatocellular carcinoma: A multicenter analysis versus ALBI score.

BACKGROUND: The Albumin-Bilirubin (ALBI) score, widely used in predicting long-term prognosis for patients with hepatocellular carcinoma (HCC), has limitations due to serum albumin variability. This study aimed to develop and validate the Prealbumin-Bilirubin (preALBI) score as a reliable alternative. METHODS: A multicenter cohort of HCC patients who underwent hepatectomy was randomly divided into the training and validation cohorts. The preALBI score was developed using Cox regression models within the training cohort, incorporating serum prealbumin and bilirubin levels as crucial determinants. The survival predictive accuracy was evaluated and compared between the preALBI score with two other staging systems, including the ALBI score and the Child-Pugh grade. RESULTS: A total of 2409 patients were enrolled. In the training cohort, the preALBI score demonstrated superior performance in predicting long-term survival after hepatectomy. The preALBI score was associated with the best monotonicity of gradients (linear trend χ2: 72.84) and homogeneity (likelihood ratio χ2: 74.69), and the highest discriminatory ability (the areas under curves for 1-, 3-, and 5-year mortality: 0.663, 0.654, and 0.644, respectively). In addition, the preALBI was the most informative staging system in predicting survival (Akaike information criterion: 11325.65).The results remained consistent in both training and validation cohorts, indicating its reliable performance across different populations. CONCLUSION: The preALBI score, leveraging the stability of prealbumin, represents a promising tool for better patient stratification, providing more accurate prognostic predictions than the ALBI score and the Child-Pugh grade.

Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma: A prospective multicenter cohort study.

BACKGROUND: Cancer-related fatigue (CRF) is a common and debilitating symptom experienced by patients with advanced-stage cancer, especially those undergoing antitumor therapy. This study aimed to evaluate the efficacy and safety of Renshenguben (RSGB) oral solution, a ginseng-based traditional Chinese medicine, in alleviating CRF in patients with advanced hepatocellular carcinoma (HCC) receiving antitumor treatment. METHODS: In this prospective, open-label, controlled, multicenter study, patients with advanced HCC at BCLC stage C and a brief fatigue inventory (BFI) score of ≥ 4 were enrolled. Participants were assigned to the RSGB group (RSGB, 10 mL twice daily) or the control group (with supportive care). Primary and secondary endpoints were the change in multidimensional fatigue inventory (MFI) score, and BFI and functional assessment of cancer therapy-hepatobiliary (FACT-Hep) scores at weeks 4 and 8 after enrollment. Adverse events (AEs) and toxicities were assessed. RESULTS: A total of 409 participants were enrolled, with 206 assigned to the RSGB group. At week 4, there was a trend towards improvement, but the differences were not statistically significant. At week 8, the RSGB group exhibited a significantly lower MFI score (P < 0.05) compared to the control group, indicating improved fatigue levels. Additionally, the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8 (P < 0.05). Subgroup analyses among patients receiving various antitumor treatments showed similar results. Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI, BFI, and FACT-Hep scores at week 8. No serious drug-related AEs or toxicities were observed. CONCLUSIONS: RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period, with no discernible toxicities. These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

Impact of Hepatic Pedicle Clamping on Long-Term Survival Following Hepatectomy for Hepatocellular Carcinoma: Stratified Analysis Based on Intraoperative Blood Transfusion Status.

BACKGROUND: Hepatic pedicle clamping (HPC) is frequently utilized during hepatectomy to reduce intraoperative bleeding and diminish the need for intraoperative blood transfusion (IBT). The long-term prognostic implications of HPC following hepatectomy for hepatocellular carcinoma (HCC) remain under debate. This study aims to elucidate the association between HPC and oncologic outcomes after HCC resection, stratified by whether IBT was administered. PATIENTS AND METHODS: Prospectively collected data on patients with HCC who underwent curative resection from a multicenter database was studied. Patients were stratified into two cohorts on the basis of whether IBT was administered. The impact of HPC on long-term overall survival (OS) and recurrence-free survival (RFS) between the two cohorts was assessed by univariable and multivariable Cox regression analyses. RESULTS: Of 3362 patients, 535 received IBT. In the IBT cohort, using or not using HPC showed no significant difference in OS and RFS outcomes (5-year OS and RFS rates 27.9% vs. 24.6% and 13.8% vs. 12.0%, P = 0.810 and 0.530). However, in the non-IBT cohort of 2827 patients, the HPC subgroup demonstrated significantly decreased OS (5-year 45.9% vs. 56.5%, P < 0.001) and RFS (5-year 24.7% vs. 33.3%, P < 0.001) when compared with the subgroup without HPC. Multivariable Cox regression analysis identified HPC as an independent risk factor of OS and RFS [hazard ratios (HR) 1.16 and 1.12, P = 0.024 and 0.044, respectively] among patients who did not receive IBT. CONCLUSIONS: The impact of HPC on the oncological outcomes following hepatectomy for patients with HCC differed significantly whether IBT was administered, and HPC adversely impacted on long-term survival for patients without receiving IBT during hepatectomy.

Prognostic Value of Serum α-Fetoprotein Level as an Important Characteristic of Tumor Biology for Patients Undergoing Liver Resection of Early-Stage Hepatocellular Carcinoma (BCLC Stage 0/A): A Large Multicenter Analysis.

BACKGROUND AND OBJECTIVE: According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, tumor burden and liver function, but not tumor biology, are the key factors in determining tumor staging and treatment modality, and evaluating treatment prognosis. The serum α-fetoprotein (AFP) level is an important characteristic of hepatocellular carcinoma (HCC) biology, and we aimed to evaluate its prognostic value for patients undergoing liver resection of early-stage HCC. METHODS: Patients who underwent curative liver resection for early-stage HCC were identified from a multi-institutional database. Patients were divided into three groups according to preoperative AFP levels: low (< 400 ng/mL), high (400-999 ng/mL), and extremely-high (≥ 1000 ng/mL) AFP groups. Overall survival (OS) and recurrence rates were compared among these three groups. RESULTS: Among 1284 patients, 720 (56.1%), 262 (20.4%), and 302 (23.5%) patients had preoperative low, high, and extremely-high AFP levels, respectively. The cumulative 5-year OS and recurrence rates were 71.3 and 38.9% among patients in the low AFP group, 66.3 and 48.5% in the high AFP group, and 45.7 and 67.2% in the extremely-high AFP group, respectively (both p < 0.001). Multivariate Cox regression analysis identified both high and extremely-high AFP levels to be independent risk factors of OS (hazard ratio [HR] 1.275 and 1.978, 95% confidence interval [CI] 1.004-1.620 and 1.588-2.464, respectively; p = 0.047 and p < 0.001, respectively) and recurrence (HR 1.290 and 2.050, 95% CI 1.047-1.588 and 1.692-2.484, respectively; p = 0.017 and p < 0.001, respectively). CONCLUSIONS: This study demonstrated the important prognostic value of preoperative AFP levels among patients undergoing resection for early-stage HCC. Incorporating AFP to prognostic estimation of the BCLC algorithm can help guide individualized risk stratification and identify neoadjuvant/adjuvant treatment necessity.

Clinical characteristics of hospitalized patients with Nocardia genus detection by metagenomic next generation sequencing in a tertiary hospital from southern China.

OBJECTIVE: As an opportunistic pathogen, Nocardia often occurring in the immunocompromised hosts. As the unspecifc clinical presentation and low identification rate of the culture dependent methods, Nocardia infection may be under-diagnosis. Recent study have reported physicians could benefit from metagenomic next-generation sequencing (mNGS) in Nocardia diagnosis. Herein, we present patients with a positive detection of nocardiosis in mNGS, aiming to provide useful information for an differential diagnosis and patients management. METHODS: A total of 3756 samples detected for mNGS from March 2019 to April 2022 at the Fifth Affifiliated Hospital of Sun Yat-sen University, were screened. Clinical records, laboratory finding, CT images and mNGS results were reviewed for 19 patients who were positive for Nocardia genus. RESULTS: Samples from low respiratory tract obtained by bronchoscope took the major part of the positive (15/19). 12 of 19 cases were diagnosis as Nocardiosis Disease (ND) and over half of the ND individuals (7/12) were geriatric. Nearly all of them (10/12) were immunocompetent and 2 patients in ND group were impressively asymptomatic. Cough was the most common symptom. Nocardia cyriacigeorgica (4/12) was more frequently occurring in ND, followed by Nocardia abscessus (3/12). There are 3 individuals detected more than one kind of Nocardia species (Supplementary table 1). Except one with renal failure and one allergic to sulfamethoxazole, all of them received co-sulfonamide treatment and relieved eventually. CONCLUSION: Our study deciphered the clinical features of patients with positive nocardiosis detected by mNGS. Greater attention should be paid to the ND that occurred in the immunocompetent host and the geriatric. Due to the difficulties in establishing diagnosis of Nocardiosis disease, mNGS should play a much more essential role for a better assessment in those intractable cases. Co-sulfonamide treatment should still be the first choice of Nocardiosis disease.

Association of tumor morphology with long-term prognosis after liver resection for patients with a solitary huge hepatocellular carcinoma-a multicenter propensity score matching analysis.

Background: A solitary hepatocellular carcinoma (HCC) without macrovascular invasion and distant metastasis, regardless of tumor size, is currently classified as early-stage disease by the latest Barcelona Clinic Liver Cancer (BCLC) staging system. While the preferred treatment is surgical resection, the association of tumor morphology with long-term survival outcomes after liver resection for a solitary huge HCC of ≥10 cm has not been defined. Methods: Patients who underwent curative liver resection for a solitary huge HCC were identified from a multicenter database. Preoperative imaging findings were used to define spherical- or ellipsoidal-shaped lesions with smooth edges as balloon-shaped HCCs (BS-HCCs); out-of-shape lesions or lesions of any shape with matt edges were defined as non-balloon-shaped HCCs (NBS-HCCs). The two groups of patients with BS-HCCs and NBS-HCCs were matched in a 1:1 ratio using propensity score matching (PSM). Clinicopathologic characteristics, long-term overall survival (OS) and recurrence-free survival (RFS) were assessed. Results: Among patients with a solitary huge HCC, 74 pairs of patients with BS-HCC and NBS-HCC were matched. Tumor pathological features including proportions of microvascular invasion, satellite nodules, and incomplete tumor encapsulation in the BS-HCC group were lower than the NBS-HCC group. At a median follow-up of 50.7 months, median OS and RFS of all patients with a solitary huge HCC after PSM were 27.8 and 10.1 months, respectively. The BS-HCC group had better median OS and RFS than the NBS-HCC group (31.9 vs. 21.0 months, P=0.01; and 19.7 vs. 6.4 months, P=0.015). Multivariate analyses identified BS-HCC as independently associated with better OS (HR =0.592, P=0.009) and RFS (HR =0.633, P=0.013). Conclusions: For a solitary huge HCC, preoperative imaging on tumor morphology was associated with prognosis following resection. In particular, patients with BS-HCCs had better long-term survival following liver resection versus patients with large NBS-HCCs.

Postoperative infectious complications following laparoscopic versus open hepatectomy for hepatocellular carcinoma: a multicenter propensity score analysis of 3876 patients.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a common indication for hepatectomy that is often complicated by postoperative complication. The authors sought to investigate the relationship between the open with laparoscopic approach of hepatectomy and incidences of postoperative infectious complications. PATIENTS AND METHODS: Using a multicenter database, HCC patients who underwent laparoscopic hepatectomy (LH) or open hepatectomy (OH) were reviewed and analyzed. Propensity score matching (PSM), inverse probability of treatment weight (IPTW), and multivariate logistic regression analyses were utilized to assess the association of the operative approach with postoperative infectious complications, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI). RESULTS: Among 3876 patients, 845 (21.8%) and 3031 (78.2%) patients underwent LH and OH, respectively. The overall incidence of infection was 6.9 versus 14.6% among patients who underwent LH versus OH, respectively ( P <0.001). Of note, the incidences of incisional SSI (1.8 vs. 6.3%, P <0.001), organ/space SSI (1.8 vs. 4.6%, P <0.001), and RI (3.8 vs. 9.8%, P <0.001) were all significantly lower among patients who underwent LH versus OH. After PSM (6.9, 1.8, 1.8, and 3.8% vs. 18.5, 8.4, 5.2, and 12.8%, respectively) and IPTW (9.5, 2.3, 2.1, and 5.5% vs. 14.3, 6.3, 4.5, and 9.8%, respectively), LH remained associated with statistically lower incidences of all types of infectious complications. After adjustment for other confounding factors on multivariate analyses, LH remained independently associated with lower incidences of overall infection, incisional SSI, organ/space SSI, and RI in the overall, PSM, and IPTW cohorts, respectively. CONCLUSION: Compared with open approach, laparoscopic approach was independently associated with lower incidences of postoperative infectious complications following hepatectomy for HCC.

Role of pyroptosis in hemostasis activation in sepsis.

Sepsis is frequently associated with hemostasis activation and thrombus formation, and systematic hemostatic changes are associated with a higher risk of mortality. The key events underlying hemostasis activation during sepsis are the strong activation of innate immune pathways and the excessive inflammatory response triggered by invading pathogens. Pyroptosis is a proinflammatory form of programmed cell death, that defends against pathogens during sepsis. However, excessive pyroptosis can lead to a dysregulation of host immune responses and organ dysfunction. Recently, pyroptosis has been demonstrated to play a prominent role in hemostasis activation in sepsis. Several studies have demonstrated that pyroptosis participates in the release and coagulation activity of tissue factors. In addition, pyroptosis activates leukocytes, endothelial cells, platelets, which cooperate with the coagulation cascade, leading to hemostasis activation in sepsis. This review article attempts to interpret the molecular and cellular mechanisms of the hemostatic imbalance induced by pyroptosis during sepsis and discusses potential therapeutic strategies.

Comparisons of coagulation characteristics between elderly and non-elderly patients with sepsis: A prospective study.

BACKGROUND: A blunt host defense response in older patients may contribute to different coagulation responses during sepsis. We aimed to investigate the differences in coagulation parameters between elderly and non-elderly patients with sepsis. METHODS: Adult patients diagnosed with sepsis within 24 hours after admission to the intensive care unit between September 2018 and December 2020 were prospectively enrolled. Patients were categorized into the adult (18-64 years) and elderly (age ≥65 years) groups. Conventional coagulation parameters and inflammatory markers were measured on intensive care unit admission and on Days 3 and 7. Thromboelastography was performed on intensive care unit admission. The differences in the coagulation parameters between the 2 groups were evaluated. The adult and elderly patients were matched to adjust for baseline characteristics. Correlations between inflammatory markers and coagulation-related parameters were also analyzed. RESULTS: Of the 567 patients, 303 (53.4%) were elderly. Compared with adult patients, elderly patients had lower prothrombin time elevation, lower fibrinogen, D-dimer, and fibrin/Fib degradation product levels, and lower proportion of disseminated intravascular coagulation on intensive care unit admission; and, they had lower dynamic platelet, lower fibrinogen, and D-dimer levels during the first week in the intensive care unit. Thromboelastography parameters were generally within the normal range, although elderly patients had lower R and K values and a higher alpha angle. Comparisons of coagulation parameters between the 2 groups revealed similar results in the matched cohort. The inflammatory markers correlated with prothrombin time, activated partial thromboplastin time, and antithrombin III. CONCLUSION: Elderly patients had milder coagulation activation, accompanied by a decreased inflammatory response during sepsis, compared to non-elderly patients.

Unsupervised construction of gene regulatory network based on single-cell multi-omics data of colorectal cancer.

Identifying gene regulatory networks (GRNs) at the resolution of single cells has long been a great challenge, and the advent of single-cell multi-omics data provides unprecedented opportunities to construct GRNs. Here, we propose a novel strategy to integrate omics datasets of single-cell ribonucleic acid sequencing and single-cell Assay for Transposase-Accessible Chromatin using sequencing, and using an unsupervised learning neural network to divide the samples with high copy number variation scores, which are used to infer the GRN in each gene block. Accuracy validation of proposed strategy shows that approximately 80% of transcription factors are directly associated with cancer, colorectal cancer, malignancy and disease by TRRUST; and most transcription factors are prone to produce multiple transcript variants and lead to tumorigenesis by RegNetwork database, respectively. The source code access are available at: https://github.com/Cuily-v/Colorectal_cancer.

Quantitative CT Metrics for the Prediction of Therapeutic Effect in Asthma.

Background: Few studies have explored the correlation between asthma medication and features on HRCT images. We aim to analyse the differences and temporal changes of lung function and airway resistance in asthma with diverse HRCT phenotypes in a short period after inhalation of budesonide/formoterol. Method: This observational study recruited 55 adult patients with varying severities of asthma. We performed detailed airway metrics measurements of chest CT scans, such as airway wall thickness (WT), wall area percentage (WA%), wall thickness percentage (T/OR), and airways with an inner perimeter of 10 mm (Pi10). The effect of lung structural features on asthma medication response was explored according to the WA% and T/OR twelve hours post-drug administration. Using multivariable regression models, we then assessed the influence of WA% on lung function. Results: WA% (p < 0.001) and T/OR (p < 0.001) significantly increased in asthma than in healthy control subjects. Compared to mild asthma, airway walls were further thickened (WA%, p = 0.023; T/OR: p = 0.029) and associated with lumen narrowing (Pi10, p = 0.055) in moderate to severe asthma. WA% and T/OR correlated well with lung function (FEV1, FVC, MMEF, and PEF) and airway resistance (R5, R20, Rp, and Fres). Regression analysis showed that MEF25 decreased with increasing age and WA% (R2 = 0.58, p < 0.001). Patients with thickened airway walls experienced a maximal increase in FVC, FEV1, and PEF at 2 h (p < 0.001) and a maximal decrease of R5, Z5, and Rp at 2 h (p < 0.001) in those with a thickened airway pattern. Conclusions: Asthma patients with different bronchial wall thicknesses exhibited variable lung function changes. Specifically, patients with thick airway wall patterns were more sensitive to inhaled budesonide in the short term.

Unfractionated Heparin Protects Microcirculation in Endotoxemic Rats by Antagonizing Histones.

INTRODUCTION: Levels of extracellular histones are highly increased in sepsis and may facilitate microcirculatory dysfunction. Unfractionated heparin (UFH) binds histones and neutralizes their cytotoxicity. We investigated the effect of UFH on microcirculatory dysfunction by interacting with extracellular histones in endotoxemic rats. METHODS: Twenty-four Wistar rats were randomly divided into three groups: control, lipopolysaccharide (LPS) group, and LPS + UFH group. In the LPS and LPS + UFH groups, 10 mg/kg LPS was injected to induce endotoxemia, and 100 IU/kg/h UFH was administered intravenously in the LPS + UFH group. The rats underwent midline laparotomy, and then intestinal microcirculation was evaluated using an incident dark field microscope. Circulating histones and microstructures of the rat intestinal microvascular endothelium were also detected. Additionally, the antagonistic effect of UFH on histone-induced cytotoxicity was investigated in human intestinal microvascular endothelial cells. RESULTS: UFH protected the microcirculation of the intestinal serosa and mucosa in endotoxemic rats, as evidenced by increased total vessel density, perfused vessel density, and proportion of perfused vessels of both the serosa and mucosa, and increased microcirculatory flow index of the mucosa in the LPS + UFH group. UFH treatment decreased the levels of circulating histones and alleviated intestinal microvascular endothelial injuries in endotoxemic rats. Furthermore, UFH inhibited histone cytotoxicity in vitro. CONCLUSIONS: UFH attenuated microcirculatory dysfunction in endotoxemic rats by antagonizing extracellular histones, thereby providing a potential therapeutic strategy for sepsis.

Association of Concurrent Metabolic Syndrome with Long-term Oncological Prognosis Following Liver Resection for Hepatocellular Carcinoma Among Patients with Chronic Hepatitis B Virus Infection: A Multicenter Study of 1753 Patients.

BACKGROUND: Although hepatitis B virus (HBV) infection remains the main cause of hepatocellular carcinoma (HCC) worldwide, metabolic syndrome, with its increase in prevalence, has become an important and significant risk factor for HCC. This study was designed to investigate the association of concurrent metabolic syndrome with long-term prognosis following liver resection for patients with HBV-related HCC. METHODS: From a Chinese, multicenter database, HBV-infected patients who underwent curative resection for HCC between 2010 and 2020 were identified. Long-term oncological prognosis, including overall survival (OS), recurrence-free survival (RFS), and early (≤2 years of surgery) and late (>2 years) recurrences were compared between patients with versus those without concurrent metabolic syndrome. RESULTS: Of 1753 patients, 163 (9.3%) patients had concurrent metabolic syndrome. Compared with patients without metabolic syndrome, patients with metabolic syndrome had poorer 5-year OS (47.5% vs. 61.0%; P = 0.010) and RFS (28.3% vs. 44.2%; P = 0.003) rates and a higher 5-year overall recurrence rate (67.3% vs. 53.3%; P = 0.024). Multivariate analysis revealed that concurrent metabolic syndrome was independently associated with poorer OS (hazard ratio: 1.300; 95% confidence interval: 1.018-1.660; P = 0.036) and RFS (1.314; 1.062-1.627; P = 0.012) rates, and increased rates of late recurrence (hazard ratio: 1.470; 95% confidence interval: 1.004-2.151; P = 0.047). CONCLUSIONS: In HBV-infected patients with HCC, concurrent metabolic syndrome was associated with poorer postoperative long-term oncologic survival outcomes. These results suggested that patients with metabolic syndrome should undergo enhanced surveillance for tumor recurrence even after 2 years of surgery to early detect late HCC recurrence. Whether improving metabolic syndrome can reduce postoperative recurrence of HCC deserves further exploration.