Predicting lncRNA-disease associations based on combining selective similarity matrix fusion and bidirectional linear neighborhood label propagation.

Recent studies have revealed that long noncoding RNAs (lncRNAs) are closely linked to several human diseases, providing new opportunities for their use in detection and therapy. Many graph propagation and similarity fusion approaches can be used for predicting potential lncRNA-disease associations. However, existing similarity fusion approaches suffer from noise and self-similarity loss in the fusion process. To address these problems, a new prediction approach, termed SSMF-BLNP, based on organically combining selective similarity matrix fusion (SSMF) and bidirectional linear neighborhood label propagation (BLNP), is proposed in this paper to predict lncRNA-disease associations. In SSMF, self-similarity networks of lncRNAs and diseases are obtained by selective preprocessing and nonlinear iterative fusion. The fusion process assigns weights to each initial similarity network and introduces a unit matrix that can reduce noise and compensate for the loss of self-similarity. In BLNP, the initial lncRNA-disease associations are employed in both lncRNA and disease directions as label information for linear neighborhood label propagation. The propagation was then performed on the self-similarity network obtained from SSMF to derive the scoring matrix for predicting the relationships between lncRNAs and diseases. Experimental results showed that SSMF-BLNP performed better than seven other state of-the-art approaches. Furthermore, a case study demonstrated up to 100% and 80% accuracy in 10 lncRNAs associated with hepatocellular carcinoma and 10 lncRNAs associated with renal cell carcinoma, respectively. The source code and datasets used in this paper are available at: https://github.com/RuiBingo/SSMF-BLNP.

A vector projection similarity-based method for miRNA-disease association prediction.

[S U M M A R Y] Many miRNA-disease association prediction models incorporate Gaussian interaction profile kernel similarity (GIPS). However, the GIPS fails to consider the specificity of the miRNA-disease association matrix, where matrix elements with a value of 0 represent miRNA and disease relationships that have not been discovered yet. To address this issue and better account for the impact of known and unknown miRNA-disease associations on similarity, we propose a method called vector projection similarity-based method for miRNA-disease association prediction (VPSMDA). In VPSMDA, we introduce three projection rules and combined with logistic functions for the miRNA-disease association matrix and propose a vector projection similarity measure for miRNAs and diseases. By integrating the vector projection similarity matrix with the original one, we obtain the improved miRNA and disease similarity matrix. Additionally, we construct a weight matrix using different numbers of neighbors to reduce the noise in the similarity matrix. In performance evaluation, both LOOCV and 5-fold CV experiments demonstrate that VPSMDA outperforms seven other state-of-the-art methods in AUC. Furthermore, in a case study, VPSMDA successfully predicted 10, 9, and 10 out of the top 10 associations for three important human diseases, respectively, and these predictions were confirmed by recent biomedical resources.

LUNCRW: Prediction of potential lncRNA-disease associations based on unbalanced neighborhood constraint random walk.

Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are associated with various complex human diseases. They can serve as disease biomarkers and hold considerable promise for the prevention and treatment of various diseases. The traditional random walk algorithms generally exclude the effect of non-neighboring nodes on random walking. In order to overcome the issue, the neighborhood constraint (NC) approach is proposed in this study for regulating the direction of the random walk by computing the effects of both neighboring nodes and non-neighboring nodes. Then the association matrix is updated by matrix multiplication for minimizing the effect of the false negative data. The heterogeneous lncRNA-disease network is finally analyzed using an unbalanced random walk method for predicting the potential lncRNA-disease associations. The LUNCRW model is therefore developed for predicting potential lncRNA-disease associations. The area under the curve (AUC) values of the LUNCRW model in leave-one-out cross-validation and five-fold cross-validation were 0.951 and 0.9486 ± 0.0011, respectively. Data from published case studies on three diseases, including squamous cell carcinoma, hepatocellular carcinoma, and renal cell carcinoma, confirmed the predictive potential of the LUNCRW model. Altogether, the findings indicated that the performance of the LUNCRW method is superior to that of existing methods in predicting potential lncRNA-disease associations.

Novel mesothelin-targeted chimeric antigen receptor-modified UNKT cells are highly effective in inhibiting tumor progression.

The design of chimeric antigen receptors (CAR) significantly enhances the antitumor efficacy of T cells. Although some CAR-T products have been approved by FDA in treating hematological tumors, adoptive immune therapy still faces many difficulties and challenges in the treatment of solid tumors. In this study, we reported a new strategy to treat solid tumors using a natural killer-like T (NKT) cell line which showed strong cytotoxicity to lyse 15 cancer cell lines, safe to normal cells and had low or no Graft-versus-host activity. We thus named it as universal NKT (UNKT). In both direct and indirect 3D tumor-like organ model, UNKT showed efficient tumor-killing properties, indicating that it could penetrate the microenvironment of solid tumors. In mesothelin (MSLN)-positive tumor cells (SKOV-3 and MCF-7), MSLN targeting CAR modified-UNKT cells had enhanced killing potential against MSLN positive ovarian cancer compared with the wild type UNKT, as well as MSLN-CAR-T cells. Compared with CAR-T, Single-cell microarray 32-plex proteomics revealed CAR-UNKT cells express more effector cytokines, such as perforin and granzyme B, and less interleukin-6 after activation. Moreover, our CAR-UNKT cells featured in more multifunctionality than CAR-T cells. CAR-UNKT cells also demonstrated strong antitumor activity in mouse models of ovarian cancer, with the ability to migrate and infiltrate the tumor without inducing immune memory. The fast-in and -out, enhanced and prolonged tumor killing properties of CAR-UNKT suggested a novel cure option of cellular immunotherapy in the treatment of MSLN-positive solid tumors.

HBRWRLDA: predicting potential lncRNA-disease associations based on hypergraph bi-random walk with restart.

Accumulating evidence indicates that the regulation of long non-coding RNAs (lncRNAs) is closely related to a variety of diseases. Identifying meaningful lncRNA-disease associations will help to contribute to the understanding of the molecular mechanisms underlying these diseases. However, only a limited number of associations between lncRNAs and diseases have been inferred from traditional biological experiments due to the high cost and highly specialized. Therefore, computational methods are increasingly used to reduce time of biological experiments and complement biological research. In this paper, a computational method called HBRWRLDA is proposed to predict lncRNA-disease associations. First, HBRWRLDA models the relationships between multiple nodes using hypergraphs, which allows HBRWRLDA to integrate the expression similarity of lncRNAs and the semantic similarity of diseases to construct hypergraphs. Then, a bi-random walk on hypergraphs is used to predict potential lncRNA-disease associations. HBRWRLDA achieves a higher area under the curve value of 0.9551 and [Formula: see text], respectively, compared with the other five advanced methods under the framework of one-leave cross validation (LOOCV) and five-fold cross-validation (5-fold CV). In addition, the prediction effect of HBRWRLDA was confirmed case studies of three diseases: renal cell carcinoma, gastric cancer, and hepatocellular carcinoma. Case studies demonstrates the capacity of HBRWRLDA to identify potentially disease-associated lncRNAs. Overall, HBRWRLDA is excellent at predicting potential lncRNA-disease associations and could be useful in conducting further biological experiments by helping researchers identify candidates of lncRNA-disease association.

Efficacy and safety of over-the-scope clips (OTSC®) for closure of gastrointestinal fistulas less than 2 cm.

BACKGROUND AND AIM: Gastrointestinal (GI) fistula is a complication of surgery associated with potential morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of over-the-scope clips (OTSC®) for closing GI fistulas. METHODS: Patients with GI fistula who underwent endoscopic closure using OTSC® were enrolled. The clinical date, duration, location and diameter of the fistula, technical success of the OTSC®, complications, follow-up periods and clinical success were recorded. RESULTS: A total of 98 patients with GI fistula underwent OTSC® closure. Their median age was 50 years (range 16-88 years), and the median duration of the fistula was 185.5 days (range 12-3129 days). The mean diameter of fistula was 4.64 ± 1.16 mm. Technical success was achieved in 100% of the patients, and clinical success was achieved in 55.10% (54/98) of the patients after a median follow-up of 168.5 days (range 36-424 days). Based on the location of the fistula, the clinical success rate of treating a fistula in the esophagus and small intestine was 100%, followed by the rectum (70%, 7/10), anastomotic stoma (61.90%, 13/21), duodenum (53.33%, 8/15), colon (47.06%, 8/17), stomach (43.47%, 10/23) and appendix stump (33.33%, 2/6). The duration of the fistula (HR 3.609, 95% CI 1.387-9.387, P = 0.009) was a risk factor for clinical success by multivariate analysis. CONCLUSION: OTSC® is a safe and efficient treatment for GI fistula and is a potential alternative to the surgical approach. Before OTSC® placement, the duration of the fistula should be assessed since it is related to the successful closures with OTSC®.

DRPADC: A novel drug repositioning algorithm predicting adaptive drugs for COVID-19.

Given that the usual process of developing a new vaccine or drug for COVID-19 demands significant time and funds, drug repositioning has emerged as a promising therapeutic strategy. We propose a method named DRPADC to predict novel drug-disease associations effectively from the original sparse drug-disease association adjacency matrix. Specifically, DRPADC processes the original association matrix with the WKNKN algorithm to reduce its sparsity. Furthermore, multiple types of similarity information are fused by a CKA-MKL algorithm. Finally, a compressed sensing algorithm is used to predict the potential drug-disease (virus) association scores. Experimental results show that DRPADC has superior performance than several competitive methods in terms of AUC values and case studies. DRPADC achieved the AUC value of 0.941, 0.955 and 0.876 in Fdataset, Cdataset and HDVD dataset, respectively. In addition, the conducted case studies of COVID-19 show that DRPADC can predict drug candidates accurately.

Identification of diatom taxonomy by a combination of region-based full convolutional network, online hard example mining, and shape priors of diatoms.

Diatom test is one of the commonly used diagnostic methods for drowning in forensic pathology, which provides supportive evidence for drowning. However, in forensic practice, it is time-consuming and laborious for forensic experts to classify and count diatoms, whereas artificial intelligence (AI) is superior to human experts in processing data and carrying out classification tasks. Some AI techniques have focused on searching diatoms and classifying diatoms. But, they either could not classify diatoms correctly or were time-consuming. Conventional detection deep network has been used to overcome these problems but failed to detect the occluded diatoms and the diatoms similar to the background heavily, which could lead to false positives or false negatives. In order to figure out the problems above, an improved region-based full convolutional network (R-FCN) with online hard example mining and the shape prior of diatoms was proposed. The online hard example mining (OHEM) was coupled with the R-FCN to boost the capacity of detecting the occluded diatoms and the diatoms similar to the background heavily and the priors of the shape of the common diatoms were explored and introduced to the anchor generation strategy of the region proposal network in the R-FCN to locate the diatoms precisely. The results showed that the proposed approach significantly outperforms several state-of-the-art methods and could detect the diatom precisely without missing the occluded diatoms and the diatoms similar to the background heavily. From the study, we could conclude that (1) the proposed model can locate the position and identify the genera of common diatoms more accurately; (2) this method can reduce the false positives or false negatives in forensic practice; and (3) it is a time-saving method and can be introduced.

HAUBRW: Hybrid algorithm and unbalanced bi-random walk for predicting lncRNA-disease associations.

An increasing number of research shows that long non-coding RNA plays a key role in many important biological processes. However, the number of disease-related lncRNAs found by researchers remains relatively small, and experimental identification is time consuming and labor intensive. In this study, we propose a novel method, namely HAUBRW, to predict undiscovered lncRNA-disease associations. First, the hybrid algorithm, which combines the heat spread algorithm and the probability diffusion algorithm, redistributes the resources. Second, unbalanced bi-random walk, is used to infer undiscovered lncRNA disease associations. Seven advanced models, i.e. BRWLDA, DSCMF, RWRlncD, IDLDA, KATZ, Ping's, and Yang's were compared with our method, and simulation results show that the AUC of our method is more perfect than the other models. In addition, case studies have shown that HAUBRW can effectively predict candidate lncRNAs for breast, osteosarcoma and cervical cancer. Therefore, our approach may be a good choice in future biomedical research.

Current progress of source control in the management of intra-abdominal infections.

Intra-abdominal infection (IAI) is a deadly condition in which the outcome is associated with urgent diagnosis, assessment and management, including fluid resuscitation, antibiotic administration while obtaining further laboratory results, attaining precise measurements of hemodynamic status, and pursuing source control. This last item makes abdominal sepsis a unique treatment challenge. Delayed or inadequate source control is an independent predictor of poor outcomes and recognizing source control failure is often difficult or impossible. Further complicating issue in the debate is surrounding the timing, adequacy, and procedures of source control. This review evaluated and summarized the current approach and challenges in IAI management, which are the future research directions.

Clinical parameters and outcomes of necrotizing soft tissue infections secondary to gastrointestinal fistulas.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) is severe surgical infections which can occur following trauma or abdominal surgery. NSTIs secondary to gastrointestinal (GI) fistula is a rare but severe complication. METHODS: A retrospective cohort study was performed on all subjects presenting with GI fistulas associated NSTIs were included. Clinical characteristics, microbiological profile, operations performed, and outcomes of patients were analyzed. RESULTS: Between 2014 and 2017, 39 patients were finally enrolled. The mean age were 46.9 years and male were the dominant. For the etiology of fistula, 25 (64.1%) of the patients was due to trauma. Overall, in-hospital death occurred in 15 (38.5%) patients. Microbiologic findings were obtained from 31 patients and Klebsiella pneumoniae was the most common species (41.0%). Eight patients were treated with an open abdomen; negative pressure wound therapy was used in 33 patients and only 2 patients received hyperbaric oxygen therapy. Younger age and delayed abdominal wall reconstruction repair were more common in trauma than in non-trauma. Non-survivors had higher APACHE II score, less source control< 48 h and lower platelet count on admission than survivors. Multiple organ dysfunction syndrome, multidrug-resistant organisms and source control failure were the main cause of in-hospital mortality. CONCLUSIONS: Trauma is the main cause of GI fistulas associated NSTIs. Sepsis continues to be the most important factor related to mortality. Our data may assist providing enlightenment for quality improvement in these special populations.

Risk factors and clinical outcomes of hypervirulent Klebsiella pneumoniae induced bloodstream infections.

The prevalence of hypervirulent Klebsiella pneumoniae (hvKP) is high in China, but clinical characteristics and outcomes of hvKP induced bloodstream infections (BSIs) are not clear. The purpose of the present study was to determine the risk factors and clinical outcomes of hvKP-BSIs in populations admitted in a teaching hospital of Nanjing, China. The genetic characteristics and antibiotic resistance patterns of the hvKP strains were further analyzed. A retrospective study was conducted in 143 patients with K. pneumoniae BSIs at Jinling Hospital in China from September 2015 to December 2016. A positive polymerase chain reaction (PCR) amplification of the plasmid-borne rmpA (p-rmpA) and aerobactin (iucA) was identified as hvKP. Overall, 24.5% (35/143) of K. pneumoniae isolates were hvKP. Multivariate analysis implicated diabetes mellitus (OR = 3.356) and community-acquired BSIs (OR = 4.898) as independent risk factors for hvKP-BSIs. The 30-day mortality rate of the hvKP-BSIs group was 37.1% (13/35) compared with 40.7% (44/108) in the cKP-BSIs control group (P = 0.706). The KPC-producing isolates (OR = 2.851), underlying disease with gastrointestinal fistula (OR = 3.054), APACHE II score ≥ 15 (OR = 6.694) and Pitt bacteremia score ≥ 2 (OR = 6.232) at infection onset were independent predictors for 30-day mortality of K. pneumoniae bacteremia patients. A high percentage (57.1%, 20/35) of KPC-producing isolates was observed among hvKP strains and ST11 was dominant in hvKP strains (17/35, 48.6%). KPC-producing hvKP is emerging, indicating the importance of epidemiologic surveillance and clinical awareness of this pathogen.

Risk factors of surgical site infections in patients with Crohn's disease complicated with gastrointestinal fistula.

PURPOSE: Surgical site infection (SSI) is the most common complication following surgical procedures. This study aimed to determine risk factors associated with SSI in patients with Crohn's disease (CD) complicated with gastrointestinal fistula. METHODS: This was a retrospective review of patients who underwent surgical resection in gastrointestinal fistula patients with CD between January 2013 and January 2015, identified from a prospectively maintained gastrointestinal fistula database. Demographic information, preoperative medication, intraoperative findings, and postoperative outcome data were collected. Univariate and multivariate analysis was carried out to assess possible risk factors for SSI. RESULTS: A total of 118 patients were identified, of whom 75.4% were men, the average age of the patients was 34.1 years, and the average body mass index (BMI) was 18.8 kg/m2. The rate of SSI was 31.4%. On multivariate analysis, preoperative anemia (P = 0.001, OR 7.698, 95% CI 2.273-26.075), preoperative bacteria present in fistula tract (P = 0.029, OR 3.399, 95% CI 1.131-10.220), and preoperative enteral nutrition (EN) <3 months (P < 0.001, OR 11.531, 95% CI 3.086-43.079) were predictors of SSI. Notably, preoperative percutaneous abscess drainage was shown to exert protection against SSI in fistulizing CD (P = 0.037, OR 0.258, 95% CI 0.073-0.920). CONCLUSION: Preoperative anemia, bacteria present in fistula tract, and preoperative EN <3 months significantly increased the risk of postoperative SSI in gastrointestinal fistula complicated with CD. Preoperative identification of these risk factors may assist in risk assessment and then to optimize preoperative preparation and perioperative care.

Delayed Diagnosis is Associated with Early and Emergency Need for First Crohn's Disease-Related Intestinal Surgery.

BACKGROUND Increasing evidence suggests that delayed diagnosis in Crohn's disease is associated with a complicated disease course. The aim of this study was to explore the association between delayed diagnosis and the timing of the first Crohn's disease-related intestinal surgery. MATERIAL AND METHODS A retrospective study included 215 Crohn's disease patients with previous surgical history in the Department of General Surgery of Jinling Hospital, China, between January 2013 and March 2016. Data were collected on demographics, clinical characteristics, medication history, and operation history. RESULTS The time from the first appearance of Crohn's disease-related symptoms to the first intestinal surgery in the delayed diagnosis group was obviously shorter than in the non-delayed diagnosis group (26.4±28.7 months vs. 42.6±58.4 months, respectively, p=0.032). Patients in the delayed diagnosis group tended to receive more ileal resections (47.8% vs. 26.4%, respectively, p=0.002) and less ileocecal resections (22.4% vs. 37.2%, respectively, p=0.032). More patients in the delayed diagnosis group received the first Crohn's disease-related intestinal surgery as an emergency one (20.9% vs. 4.7%, respectively, p=0.001). CONCLUSIONS Delayed diagnosis is associated with early and emergency need for the first Crohn's disease-related intestinal surgery.

Association between the -159C/T polymorphism in the promoter region of the CD14 gene and sepsis: a meta-analysis.

BACKGROUND: The association between CD14-159C/T polymorphism and sepsis has been assessed but results of current studies appeared conflicting and inconstant. This analysis was aimed to determine whether the CD14-159C/T polymorphism confers susceptibility to sepsis or is associated with increased risk of death from sepsis. METHOD: The authors conducted a comprehensive search of PubMed, EMBASE, ISI Web of Science, Cochrane library, ScienceDirect, Wiley Online Library and CNKI databases according to a prespecified protocol. Language limits were restricted to English and Chinese. Two reviewers independently selected the articles and extracted relevant data onto standardized forms. Disagreements were settled by discussion and suggestions from senior consultants. The strength of association were evaluated by odds ratio (OR) and 95% confidence interval (CI). Studies failed to fit the Hardy-Weinberg-Equilibrium were excluded. RESULTS: The research identified a total of 2317 full-text articles of which 14 articles met the predefined inclusion criteria. Meta-analysis was performed for allele frequency of C versus T, as well as genotypes CC + CT versus TT (dominant model), CC versus TT + CT (recessive model), CT versus TT and CC versus TT (additive model). All control samples were in Hardy-Weinberg proportion. No significant association between CD14-159C/T polymorphism and sepsis susceptibility or mortality were detected in the overall population. Nonetheless, subgroup analysis of Asian ethnicity revealed significant association between the CD14-159C/T polymorphism and susceptibility to sepsis in additive model (CC versus TT: OR = 0.52, 95% CI 0.29-0.92, p = 0.03) and recessive model (CC versus CT + TT: OR = 0.50, 95% CI 0.30-0.84, p = 0.009). Of note, three out of the five papers included in the subgroup focused exclusively on burn ICU patients. CONCLUSIONS: This meta-analysis demonstrated that CD14-159C/T polymorphism is likely to be associated with susceptibility to sepsis in Asian population, especially for the TT genotype. However, bias may rise for etiologic reasons because the majority of subjects in the subgroup came from burn ICU. CD14-159C/T polymorphism is not relevant to sepsis mortality in any genetic models, regardless of the ethnicities. Due to the exploratory nature of the study, no adjustment for multiple testing was adopted, and therefore the results should be interpreted with precaution. Well-designed studies with larger sample size and more ethnic groups are required to further validate the results.

Laparoscopy improves clinical outcome of gastrointestinal fistula caused by Crohn's disease.

BACKGROUND: Benefits of laparoscopic surgery in the management of gastrointestinal fistula caused by Crohn disease need to be fully elucidated. We conducted this retrospective study to investigate the safety and feasibility and emphasize the advantages of laparoscopy compared with that of laparotomy for patients with gastrointestinal fistula caused by Crohn disease. MATERIALS AND METHODS: A total of 1213 patients with gastrointestinal fistula in our center were screened, and 318 qualified patients were enrolled and divided into laparoscopy (n = 122) and laparotomy (n = 196) groups. Postoperative complications, length of hospital stay, systemic stress responses to surgery, postoperative mortality, and economic burden were collected and compared. RESULTS: A total of 125 laparoscopic interventions were performed with a conversion rate of 20.0%. Fifteen versus 84 postoperative complications were obtained in laparoscopy and laparotomy groups, respectively (P = 0.0033). Total hospitalization was 22.7 d and 38.0 d in laparoscopy and laparotomy groups, respectively (P < 0.0001). Postoperative hospitalization was 10.9 d and 24.8 d in two groups, respectively (P < 0.0001). Elevation curve of serum C-reactive protein and procalcitonin in response to laparoscopy was significantly lower than that to laparotomy. Reduced postoperative mortality (P = 0.0292) and postoperative cost (P = 0.0292) were observed in laparoscopy instead of laparotomy group. CONCLUSIONS: Laparoscopic approach is safe and feasible and could improve clinical outcome in gastrointestinal fistula patients with Crohn disease.

Prediction of procalcitonin for postoperative intraabdominal infections after definitive operation of intestinal fistulae.

BACKGROUND: Inflammatory biomarkers usually start to rise earlier before the infection becomes clinically evident. This study was designed to evaluate the predictive performance of procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) counts in postoperative intraabdominal infections (IAIs) after definitive operation of intestinal fistulae. MATERIAL AND METHODS: We prospectively enrolled a total of 356 consecutive patients who underwent elective digestive tract reconstruction for gastrointestinal fistulae without existing clinical infection. Plasma PCT levels, serum CRP concentration, and WBC counts were assessed preoperatively and on postoperative days (PODs) 1, 3, 5, and 7. The predictive value of each laboratory marker for IAIs was calculated. RESULTS: The occurrence rate of IAIs after elective digestive tract reconstruction for gastrointestinal fistulae in our study was 7.3%. Both PCT levels and WBC counts were significantly higher in patients with IAIs than those in patients without IAIs on POD 1, POD 3, and POD 5, whereas CRP levels differed significantly on POD 3 and POD 5. Receiver-operating characteristics demonstrated that PCT on POD 3 had the highest diagnostic accuracy for IAIs, and the area under the curve reached 0.86, with a sensitivity of 92.0% and specificity of 74.0%. CONCLUSIONS: The value of PCT above 0.98 ng/L on POD 3 and 0.83 ng/L on POD 5 could predict the occurrence of IAIs after definitive operations for intestinal fistulae.

Monocyte subsets and monocyte-platelet aggregates: implications in predicting septic mortality among surgical critical illness patients.

BACKGROUND: Monocyte subsets and monocyte-platelet aggregates (MPAs) play important roles in inflammation. AIM: To evaluate the association between the three human monocyte subsets and their contributions to MPAs and mortality among septic patients. METHODS: Consecutive septic patients were enrolled in. Age- and gender-matched nonseptic patients were recruited as control patients. Monocyte subsets and monocyte-platelet aggregates were determined by flow cytometric analysis. RESULTS: Elevated percentage of MPAs (MPAs%) was associated with an increased risk of mortality. CONCLUSIONS: This study demonstrated increased MPAs% enables the identification of a group of septic patients at high risk of death.

Laser speckle contrast imaging for measurement of hepatic microcirculation during the sepsis: a novel tool for early detection of microcirculation dysfunction.

BACKGROUND: Sepsis is a fatal systemic inflammatory response syndrome caused by severe infection. The aim of this study was to measure hepatic microcirculation during the sepsis with laser speckle contrast imaging (LSCI), as well as investigating the underlying mechanisms. METHODS: Sepsis was induced by cecal ligation and puncture. Rats were divided into the sham group and sepsis group. The hepatic microcirculation was monitored with LSCI. In addition, hepatic endothelial function (expression of cell adhesion molecules, coagulation and vascular permeability) and neutrophils accumulation in the liver were compared between the two groups. RESULTS: During the sepsis, hepatic microcirculation decreased dramatically (290.3±70.1 LSPU (laser speckle perfusion units) at baseline vs. 230.4±60.7 LSPU at 12h vs. 125.2±25.4 LSPU at 48h, P<0.001). The rats developed hyperbilirubinemia since 6h. In the early phase of sepsis, the accumulation of neutrophils and formation of microthrombus increased rapidly. In the late phase, hepatic neutrophils accumulation was already at its maximum level. Meanwhile, the endothelial coagulation status shifted from procoagulation to anticoagulation. The vascular leakage was involved in the microcirculation dysfunction since 12h after sepsis. CONCLUSIONS: Hepatic microcirculation dysfunction occurs early during the sepsis and is associated with liver injury. This microcirculation dysfunction is due to neutrophil-endothelium interactions, microthrombus formation and vascular leakage.